Sample records for shift select lever
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Beta-adrenoreceptor blockade abolishes atomoxetine-induced risk taking.
Yang, Fan Nils; Pan, Jing Samantha; Li, Xinwang
2016-01-01
Clinical studies have shown that patients with exaggerated risk-taking tendencies have high baseline levels of norepinephrine. In this work, we systemically manipulated norepinephrine levels in rats and studied their behavioral changes in a probabilistic discounting task, which is a paradigm for gauging risk taking. This study aims to explore the effects of the selective norepinephrine reuptake inhibitor (atomoxetine at doses of 0.6, 1.0 and 1.8 mg/kg), and receptor selective antagonists (propranolol at a single dose of 1.0/kg, and prazosin at a single dose of 0.1 mg/kg), on risk taking using a probabilistic discounting task. In this task, there were two levers available to rats: pressing the 'small/certain' lever guaranteed a single food pellet, and pressing the 'large/risky' lever yielded either four pellets or none. The probability of receiving four food pellets decreased across the four experimental blocks from 100% to 12.5%. Atomoxetine increased the tendency to choose the large/risky lever. It significantly reduced the lose-shift effect (i.e. pressing a different lever after losing a trial), but did not affect the win-stay effect (i.e. pressing the same lever after winning a trial). Furthermore, co-administration of beta-adrenoreceptor antagonist, propranolol, eliminated the effects of atomoxetine on risk taking and the lose-shift effect; but co-administration of alpha1-adrenoreceptor antagonist, prazosin, did not. Atomoxetine boosted NE levels and increased risk taking. This was because atomoxetine decreased rats' sensitivity to losses. These effects were likely mediated by beta-adrenoreceptor. Copyright © 2015 Elsevier Inc. All rights reserved.
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Requejo, Philip Santos; Lee, Sharon E; Mulroy, Sara J; Haubert, Lisa Lighthall; Bontrager, Ernest L; Gronley, JoAnne K; Perry, Jacquelin
2008-01-01
Background/Objective: The high demand on the upper limbs during manual wheelchair (WC) use contributes to a high prevalence of shoulder pathology in people with spinal cord injury (SCI). Lever-activated (LEVER) WCs have been presented as a less demanding alternative mode of manual WC propulsion. The objective of this study was to evaluate the shoulder muscle electromyographic activity and propulsion characteristics in manual WC users with SCI propelling a standard pushrim (ST) and LEVER WC design. Methods: Twenty men with complete injuries (ASIA A or B) and tetraplegia (C6, n = 5; C7, n = 7) or paraplegia (n = 8) secondary to SCI propelled ST and LEVER WCs at 3 propulsion conditions on a stationary ergometer: self-selected free, self-selected fast, and simulated graded resistance. Average velocity, cycle distance, and cadence; median and peak electromyographic intensity; and duration of electromyography of anterior deltoid, pectoralis major, supraspinatus, and infraspinatus muscles were compared between LEVER and ST WC propulsion. Results: Significant decreases in pectoralis major and supraspinatus activity were recorded during LEVER compared with ST WC propulsion. However, anterior deltoid and infraspinatus intensities tended to increase during LEVER WC propulsion. Participants with tetraplegia had similar or greater anterior deltoid, pectoralis major, and infraspinatus activity for both ST and LEVER WC propulsion compared with the men with paraplegia. Conclusions: Use of the LEVER WC reduced and shifted the shoulder muscular demands in individuals with paraplegia and tetraplegia. Further studies are needed to determine the impact of LEVER WC propulsion on long-term shoulder function. PMID:19086715
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Pauli, Wolfgang M; Clark, Alexandra D; Guenther, Heidi J; O'Reilly, Randall C; Rudy, Jerry W
2012-06-20
Evidence suggests that two regions of the striatum contribute differential support to instrumental response selection. The dorsomedial striatum (DMS) is thought to support expectancy-mediated actions, and the dorsolateral striatum (DLS) is thought to support habits. Currently it is unclear whether these regions store task-relevant information or just coordinate the learning and retention of these solutions by other brain regions. To address this issue, we developed a two-lever concurrent variable-interval reinforcement operant conditioning task and used it to assess the trained rat's sensitivity to contingency shifts. Consistent with the view that these two regions make different contributions to actions and habits, injecting the NMDA antagonist DL-AP5 into the DMS just prior to the shift impaired the rat's performance but enhanced performance when injected into the DLS. To determine if these regions support memory content, we first trained rats on a biased concurrent schedule (Lever 1: VI 40" and Lever 2: VI 10"). With the intent of "erasing" the memory content stored in striatum, after this training we inhibited the putative memory-maintenance protein kinase C isozyme protein kinase Mζ (PKMζ). Infusing zeta inhibitory peptide (ZIP) into the DLS enhanced the rat's ability to adapt to the contingency shift 2 d later, whereas injecting it into the DMS had the opposite effect. Infusing GluR2(3Y) into the DMS 1 h before ZIP infusions prevented ZIP from impairing the rat's sensitivity to the contingency shift. These results support the hypothesis that the DMS stores information needed to support actions and the DLS stores information needed to support habits.
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Yohn, Samantha E; Reynolds, Shanika; Tripodi, Giuseppe; Correa, Merce; Salamone, John D
2018-04-16
Motivated behaviors often are characterized by a high degree of behavioral activation and work output, and organisms frequently make effort-related decisions based upon cost/benefit analyses. Moreover, people with depression and other disorders frequently show effort-related motivational symptoms, such as anergia, psychomotor retardation, and fatigue. Tasks measuring effort-related choice are being used as animal models of these motivational symptoms. The present studies characterized the ability of the monoamine oxidase -B (MAO-B) inhibitor deprenyl (selegiline) to enhance selection of high-effort lever pressing in rats tested on a concurrent progressive ratio (PROG)/chow feeding choice task. Deprenyl is widely used as an antiparkinsonian drug, but it also has been shown to have antidepressant effects in humans, and to induce antidepressant-like effects in traditional rodent models of depression. Systemic administration of deprenyl (1.5-12.0 mg/kg IP) shifted choice behavior, significantly increasing markers of PROG lever pressing at a moderate dose (6.0 mg/kg), and decreasing chow intake at 6.0 and 12.0 mg/kg. Intracranial injections of deprenyl into nucleus accumbens (2.0 and 4.0 μg) also increased PROG lever pressing and decreased chow intake. Microdialysis studies showed that the dose of deprenyl that was effective at increasing PROG lever pressing (6.0 mg/kg) also significantly elevated extracellular dopamine in nucleus accumbens. Thus, similar to the well-known antidepressant bupropion, deprenyl is capable of increasing selection of high-effort PROG lever pressing at doses that increase extracellular dopamine in nucleus accumbens. These studies have implications for the potential use of MAO-B inhibitors as treatments for the motivational symptoms of depression and Parkinsonism. Copyright © 2018 Elsevier B.V. All rights reserved.
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Stimulus generalization, discrimination learning, and peak shift in horses.
Dougherty, D M; Lewis, P
1991-01-01
Using horses, we investigated three aspects of the stimulus control of lever-pressing behavior: stimulus generalization, discrimination learning, and peak shift. Nine solid black circles, ranging in size from 0.5 in. to 4.5 in. (1.3 cm to 11.4 cm) served as stimuli. Each horse was shaped, using successive approximations, to press a rat lever with its lip in the presence of a positive stimulus, the 2.5-in. (6.4-cm) circle. Shaping proceeded quickly and was comparable to that of other laboratory organisms. After responding was maintained on a variable-interval 30-s schedule, stimulus generalization gradients were collected from 2 horses prior to discrimination training. During discrimination training, grain followed lever presses in the presence of a positive stimulus (a 2.5-in circle) and never followed lever presses in the presence of a negative stimulus (a 1.5-in. [3.8-cm] circle). Three horses met a criterion of zero responses to the negative stimulus in fewer than 15 sessions. Horses given stimulus generalization testing prior to discrimination training produced symmetrical gradients; horses given discrimination training prior to generalization testing produced asymmetrical gradients. The peak of these gradients shifted away from the negative stimulus. These results are consistent with discrimination, stimulus generalization, and peak-shift phenomena observed in other organisms. PMID:1940765
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Win-stay and win-shift lever-press strategies in an appetitively reinforced task for rats.
Reed, Phil
2016-12-01
Two experiments examined acquisition of win-stay, win-shift, lose-stay, and lose-shift rules by which hungry rats could earn food reinforcement. In Experiment 1, two groups of rats were trained in a two-lever operant task that required them to follow either a win-stay/lose-shift or a win-shift/lose-stay contingency. The rates of acquisition of the individual rules within each contingency differed: lose-shift and lose-stay rules were acquired faster than win-stay and win-shift rules. Contrary to a number of previous reports, the win-shift rule was acquired less rapidly than any of the other rules. In Experiment 2, the four rules were taught separately, but subjects still acquired the win-shift rule more slowly than any of the other rules.
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Beas, B. Sofia; Setlow, Barry; Bizon, Jennifer L.
2016-01-01
RATIONALE The ability to adjust response strategies when faced with changes in the environment is critical for normal adaptive behavior. Such behavioral flexibility is compromised by experimental disruption of cortical GABAergic signaling, as well as in conditions such as schizophrenia and normal aging that are characterized by cortical hyperexcitability. The current studies were designed to determine whether stimulation of GABAergic signaling using the GABA(B) receptor agonist baclofen can facilitate behavioral flexibility. METHODS Male Fischer 344 rats were trained in a set-shifting task in which they learned to discriminate between two response levers to obtain a food reward. Correct levers were signaled in accordance with two distinct response rules (Rule 1: correct lever signaled by a cue light; Rule 2: correct lever signaled by its left/right position). The order of rule presentation varied, but they were always presented sequentially, with the trials and errors to reach criterion performance on the second (set shift) rule providing the measure of behavioral flexibility. Experiments determined the effects of the GABA(B) receptor agonist baclofen (i.p., 0, 1.0, 2.5 and 4.0 mg/kg) administered acutely before the shift to the second rule. RESULTS Baclofen enhanced set-shifting performance. Control experiments demonstrated that this enhancement was not simply due to improved discrimination learning, nor was it due to impaired recall of the initial discrimination rule. CONCLUSIONS The results demonstrate that baclofen can facilitate behavioral flexibility, suggesting that GABA(B) receptor agonists may have utility for treating behavioral dysfunction in neuropsychiatric disorders. PMID:27256354
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Beas, B Sofia; Setlow, Barry; Bizon, Jennifer L
2016-07-01
The ability to adjust response strategies when faced with changes in the environment is critical for normal adaptive behavior. Such behavioral flexibility is compromised by experimental disruption of cortical GABAergic signaling, as well as in conditions such as schizophrenia and normal aging that are characterized by cortical hyperexcitability. The current studies were designed to determine whether stimulation of GABAergic signaling using the GABA(B) receptor agonist baclofen can facilitate behavioral flexibility. Male Fischer 344 rats were trained in a set-shifting task in which they learned to discriminate between two response levers to obtain a food reward. Correct levers were signaled in accordance with two distinct response rules (rule 1: correct lever signaled by a cue light; rule 2: correct lever signaled by its left/right position). The order of rule presentation varied, but they were always presented sequentially, with the trials and errors to reach criterion performance on the second (set shift) rule providing the measure of behavioral flexibility. Experiments determined the effects of the GABA(B) receptor agonist baclofen (intraperitoneal, 0, 1.0, 2.5, and 4.0 mg/kg) administered acutely before the shift to the second rule. Baclofen enhanced set-shifting performance. Control experiments demonstrated that this enhancement was not simply due to improved discrimination learning, nor was it due to impaired recall of the initial discrimination rule. The results demonstrate that baclofen can facilitate behavioral flexibility, suggesting that GABA(B) receptor agonists may have utility for treating behavioral dysfunction in neuropsychiatric disorders.
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Individual Differences in the Attribution of Incentive Salience to a Pavlovian Alcohol Cue
Villaruel, Franz R.; Chaudhri, Nadia
2016-01-01
Individual differences exist in the attribution of incentive salience to conditioned stimuli associated with food. Here, we investigated whether individual differences also manifested with a Pavlovian alcohol conditioned stimulus (CS). We compiled data from five experiments that used a Pavlovian autoshaping paradigm and tests of conditioned reinforcement. In all experiments, male, Long-Evans rats with unrestricted access to food and water were acclimated to 15% ethanol. Next, rats received Pavlovian autoshaping training, in which a 10 s presentation of a retractable lever served as the CS and 0.2 mL of 15% ethanol served as the unconditioned stimulus (US). Finally, rats underwent conditioned reinforcement tests in which nose-pokes to an active aperture led to brief presentations of the lever-CS, but nose-pokes to an inactive aperture had no consequence. Rats were categorized as sign-trackers, goal-trackers and intermediates based on a response bias score that reflected their tendencies to sign-track or goal-track at different times during training. We found that distinct groups of rats either consistently interacted with the lever-CS (“sign-trackers”) or routinely approached the port during the lever-CS (“goal-trackers”) across a majority of the training sessions. However, some individuals (“shifted sign-trackers”) with an early tendency to goal-track later shifted to comparable asymptotic levels of sign-tracking as the group identified as sign-trackers. The lever-CS functioned as a conditioned reinforcer for sign-trackers and shifted sign-trackers, but not for goal-trackers. These results provide evidence of robust individual differences in the extent to which a Pavlovian alcohol cue gains incentive salience and functions as a conditioned reinforcer. PMID:28082877
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Individual Differences in the Attribution of Incentive Salience to a Pavlovian Alcohol Cue.
Villaruel, Franz R; Chaudhri, Nadia
2016-01-01
Individual differences exist in the attribution of incentive salience to conditioned stimuli associated with food. Here, we investigated whether individual differences also manifested with a Pavlovian alcohol conditioned stimulus (CS). We compiled data from five experiments that used a Pavlovian autoshaping paradigm and tests of conditioned reinforcement. In all experiments, male, Long-Evans rats with unrestricted access to food and water were acclimated to 15% ethanol. Next, rats received Pavlovian autoshaping training, in which a 10 s presentation of a retractable lever served as the CS and 0.2 mL of 15% ethanol served as the unconditioned stimulus (US). Finally, rats underwent conditioned reinforcement tests in which nose-pokes to an active aperture led to brief presentations of the lever-CS, but nose-pokes to an inactive aperture had no consequence. Rats were categorized as sign-trackers, goal-trackers and intermediates based on a response bias score that reflected their tendencies to sign-track or goal-track at different times during training. We found that distinct groups of rats either consistently interacted with the lever-CS ("sign-trackers") or routinely approached the port during the lever-CS ("goal-trackers") across a majority of the training sessions. However, some individuals ("shifted sign-trackers") with an early tendency to goal-track later shifted to comparable asymptotic levels of sign-tracking as the group identified as sign-trackers. The lever-CS functioned as a conditioned reinforcer for sign-trackers and shifted sign-trackers, but not for goal-trackers. These results provide evidence of robust individual differences in the extent to which a Pavlovian alcohol cue gains incentive salience and functions as a conditioned reinforcer.
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Drum ring removal/installation tool
Andrade, William Andrew [Livermore, CA
2006-11-14
A handheld tool, or a pair of such tools, such as for use in removing/installing a bolt-type clamping ring on a container barrel/drum, where the clamping ring has a pair of clamping ends each with a throughbore. Each tool has an elongated handle and an elongated lever arm transversely connected to one end of the handle. The lever arm is capable of being inserted into the throughbore of a selected clamping end and leveraged with the handle to exert a first moment on the selected clamping end. Each tool also has a second lever arm, such as a socket with an open-ended slot, which is suspended alongside the first lever arm. The second lever arm is capable of engaging the selected clamping end and being leveraged with the handle to exert a second moment which is orthogonal to the first moment. In this manner, the first and second moments operate to hold the selected clamping end fixed relative to the tool so that the selected clamping end may be controlled with the handle. The pair of clamping ends may also be simultaneously and independently controlled with the use of two handles/tools so as to contort the geometry of the drum clamping ring and enable its removal/installation.
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Resurgence and alternative-reinforcer magnitude.
Craig, Andrew R; Browning, Kaitlyn O; Nall, Rusty W; Marshall, Ciara M; Shahan, Timothy A
2017-03-01
Resurgence is defined as an increase in the frequency of a previously reinforced target response when an alternative source of reinforcement is suspended. Despite an extensive body of research examining factors that affect resurgence, the effects of alternative-reinforcer magnitude have not been examined. Thus, the present experiments aimed to fill this gap in the literature. In Experiment 1, rats pressed levers for single-pellet reinforcers during Phase 1. In Phase 2, target-lever pressing was extinguished, and alternative-lever pressing produced either five-pellet, one-pellet, or no alternative reinforcement. In Phase 3, alternative reinforcement was suspended to test for resurgence. Five-pellet alternative reinforcement produced faster elimination and greater resurgence of target-lever pressing than one-pellet alternative reinforcement. In Experiment 2, effects of decreasing alternative-reinforcer magnitude on resurgence were examined. Rats pressed levers and pulled chains for six-pellet reinforcers during Phases 1 and 2, respectively. In Phase 3, alternative reinforcement was decreased to three pellets for one group, one pellet for a second group, and suspended altogether for a third group. Shifting from six-pellet to one-pellet alternative reinforcement produced as much resurgence as suspending alternative reinforcement altogether, while shifting from six pellets to three pellets did not produce resurgence. These results suggest that alternative-reinforcer magnitude has effects on elimination and resurgence of target behavior that are similar to those of alternative-reinforcer rate. Thus, both suppression of target behavior during alternative reinforcement and resurgence when conditions of alternative reinforcement are altered may be related to variables that affect the value of the alternative-reinforcement source. © 2017 Society for the Experimental Analysis of Behavior.
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Resurgence and Alternative-Reinforcer Magnitude
Craig, Andrew R.; Browning, Kaitlyn O.; Nall, Rusty W.; Marshall, Ciara M.; Shahan, Timothy A.
2017-01-01
Resurgence is defined as an increase in the frequency of a previously reinforced target response when an alternative source of reinforcement is suspended. Despite an extensive body of research examining factors that affect resurgence, the effects of alternative-reinforcer magnitude have not been examined. Thus, the present experiments aimed to fill this gap in the literature. In Experiment 1, rats pressed levers for single-pellet reinforcers during Phase 1. In Phase 2, target-lever pressing was extinguished, and alternative-lever pressing produced either five-pellet, one-pellet, or no alternative reinforcement. In Phase 3, alternative reinforcement was suspended to test for resurgence. Five-pellet alternative reinforcement produced faster elimination and greater resurgence of target-lever pressing than one-pellet alternative reinforcement. In Experiment 2, effects of decreasing alternative-reinforcer magnitude on resurgence were examined. Rats pressed levers and pulled chains for six-pellet reinforcers during Phases 1 and 2, respectively. In Phase 3, alternative reinforcement was decreased to three pellets for one group, one pellet for a second group, and suspended altogether for a third group. Shifting from six-pellet to one-pellet alternative reinforcement produced as much resurgence as suspending alternative reinforcement altogether, while shifting from six pellets to three pellets did not produce resurgence. These results suggest that alternative-reinforcer magnitude has effects on elimination and resurgence of target behavior that are similar to those of alternative-reinforcer rate. Thus, both suppression of target behavior during alternative reinforcement and resurgence when conditions of alternative reinforcement are altered may be related to variables that affect the value of the alternative-reinforcement source. PMID:28194793
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SanMiguel, Noemí; Pardo, Marta; Carratalá-Ros, Carla; López-Cruz, Laura; Salamone, John D; Correa, Mercè
2018-06-01
Motivated behavior is characterized by activation and high work output. Nucleus accumbens (Nacb) modulates behavioral activation and effort-based decision-making. Caffeine is widely consumed because of its energizing properties. This methylxanthine is a non-selective adenosine A 1 /A 2A receptor antagonist. Adenosine receptors are highly concentrated in Nacb. Adenosine agonists injected into Nacb, shift preference towards low effort alternatives. The present studies characterized effort-related effects of caffeine in a concurrent progressive ratio (PROG)/free reinforcer choice procedure that requires high levels of work output, and generates great variability among different animals. Male Sprague-Dawley rats received an acute dose of caffeine (2.5-20.0 mg/kg, IP) and 30 min later were tested in operant boxes. One group was food-restricted and had to lever pressed for high carbohydrate pellets, another group was non-food-restricted and lever pressed for a high sucrose solution. Caffeine (2.5 and 5.0 mg/kg) increased lever pressing in food-restricted animals that were already high responders. However, in non-restricted animals, caffeine (5.0 and 10.0 mg/kg) increased work output only among low responders. In fact, caffeine (10.0 and 20.0 mg/kg) in non-restricted animals, reduced lever pressing among high responders in the PROG task, and also in a different group of animals lever pressing in an easy task (fixed ratio 7 schedule) that uniformly generates high levels of responding. Caffeine did not modify sucrose preference or consumption under free access conditions. Thus, when animals do not have a homeostatic need, caffeine can help those not very intrinsically motivated to work harder for a more palatable reward. However, caffeine can disrupt performance of animals intrinsically motivated to work hard for a better reward. Copyright © 2018 Elsevier Inc. All rights reserved.
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Harper, David N; Langen, Anna-Lena; Schenk, Susan
2014-01-01
Drug discrimination studies have suggested that the subjective effects of low doses of (±)3,4-methylenedioxymethamphetamine (MDMA) are readily differentiated from those of d-amphetamine (AMPH) and that the discriminative stimulus properties are mediated by serotonergic and dopaminergic mechanisms, respectively. Previous studies, however, have primarily examined responses to doses that do not produce substantial increases in extracellular dopamine. The present study determined whether doses of MDMA that produce increases in synaptic dopamine would also produce subjective effects that were more like AMPH and were sensitive to pharmacological manipulation of D1-like receptors. A three-lever drug discrimination paradigm was used. Rats were trained to respond on different levers following saline, AMPH (0.5mg/kg, IP) or MDMA (1.5mg/kg, IP) injections. Generalization curves were generated for a range of different doses of both drugs and the effect of the D1-like antagonist, SCH23390 on the discriminative stimulus effects of different doses of MDMA was determined. Rats accurately discriminated MDMA, AMPH and saline. Low doses of MDMA produced almost exclusive responding on the MDMA lever but at doses of 3.0mg/kg MDMA or higher, responding shifted to the AMPH lever. The AMPH response produced by higher doses of MDMA was attenuated by pretreatment with SCH23390. The data suggest that low doses and higher doses of MDMA produce distinct discriminative stimuli. The shift to AMPH-like responding following administration of higher doses of MDMA, and the decrease in this response following administration of SCH23390 suggests a dopaminergic component to the subjective experience of MDMA at higher doses. Copyright © 2013 Elsevier Inc. All rights reserved.
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Justinova, Zuzana; Ferre, Sergi; Segal, Pavan N; Antoniou, Katerina; Solinas, Marcello; Pappas, Lara A; Highkin, Jena L; Hockemeyer, Jorg; Munzar, Patrik; Goldberg, Steven R
2003-12-01
Adenosine, by acting on adenosine A1 and A2A receptors, is known to antagonistically modulate dopaminergic neurotransmission. We have recently reported that nonselective adenosine receptor antagonists (caffeine and 3,7-dimethyl-1-propargylxanthine) can partially substitute for the discriminative-stimulus effects of methamphetamine. In the present study, by using more selective compounds, we investigated the involvement of A1 and A2A receptors in the adenosinergic modulation of the discriminative-stimulus effects of both cocaine and methamphetamine. The effects of the A1 receptor agonist N6-cyclopentyladenosine (CPA; 0.01-0.1 mg/kg) and antagonist 8-cyclopentyl-1,3-dimethylxanthine (CPT; 1.3-23.7 mg/kg) and the A2A receptor agonist 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine hydrochloride (CGS 21680; 0.03-0.18 mg/kg) and antagonist 3-(3-hydroxypropyl)-8-(3-methoxystyryl)-7-methyl-1-propargylxanthin phosphate disodium salt (MSX-3; 1-56 mg/kg) were evaluated in rats trained to discriminate either 1 mg/kg methamphetamine or 10 mg/kg cocaine from saline under a fixed-ratio 10 schedule of food presentation. The A1 and A2A receptor antagonists (CPT and MSX-3) both produced high levels of drug-lever selection when substituted for either methamphetamine or cocaine and significantly shifted dose-response curves of both psychostimulants to the left. Unexpectedly, the A2A receptor agonist CGS 21680 also produced drug-appropriate responding (although at lower levels) when substituted for the cocaine-training stimulus, and both CGS 21680 and the A1 receptor agonist CPA significantly shifted the cocaine dose-response curve to the left. In contrast, both agonists did not produce significant levels of drug-lever selection when substituted for the methamphetamine-training stimulus and failed to shift the methamphetamine dose-response curve. Therefore, adenosine A1 and A2A receptors appear to play important but differential roles in the modulation of the discriminative-stimulus effects of methamphetamine and cocaine.
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A wheelchair with lever propulsion control for climbing up and down stairs.
Sasaki, Kai; Eguchi, Yosuke; Suzuki, Kenji
2016-08-01
This study proposes a novel stair-climbing wheelchair based on lever propulsion control using the human upper body. Wheelchairs are widely used as supporting locomotion devices for people with acquired lower limb disabilities. However, steps and stairs are critical obstacles to locomotion, which restrict their activities when using wheelchairs. Previous research focused on power-assisted, stair-climbing wheelchairs, which were large and heavy due to its large actuators and mechanisms. In the previous research, we proposed a wheelchair with lever propulsion mechanism and presented its feasibility of climbing up the stairs. The developed stair-climbing wheelchair consists of manual wheels with casters for planar locomotion and a rotary-leg mechanism based on lever propulsion that is capable of climbing up stairs. The wheelchair also has a passive mechanism powered by gas springs for posture transition to shift the user's center of gravity between the desired positions for planar locomotion and stair-climbing. In this paper, we present an advanced study on both climbing up and going down using lever propulsion control by the user's upper body motion. For climbing down the stairs, we reassembled one-way clutches used for the rotary-leg mechanism to help a user climb down the stairs through lever operation. We also equipped the wheelchair with sufficient torque dampers. The frontal wheels were fixed while climbing down the stairs to ensure safety. Relevant experiments were then performed to investigate its performance and verify that the wheelchair users can operate the proposed lever propulsion mechanism.
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46 CFR 131.845 - Instructions for shift of steering gear.
Code of Federal Regulations, 2013 CFR
2013-10-01
... alternative steering stations must be on water-resistant material and posted at each steering station and in... gear or steering stations. (d) Each clutch, gear, wheel, lever, valve, or switch used during any shift of steering gear or steering stations must be numbered or lettered on a metal plate or painted so...
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Effects Of Methylphenidate And Morphine On Delay-Discount Functions Obtained Within Sessions
Pitts, Raymond C; McKinney, A. Patrick
2005-01-01
Four rats responded under a “self-control” procedure designed to obtain delay-discount functions within sessions. Each session consisted of seven blocks, with seven trials within each block. Each block consisted of two initial forced-choice trials followed by five free-choice trials. On choice trials, the rats could press either of two retractable levers. A press on one lever was followed by presentation of a smaller reinforcer (a single dipper presentation of a sucrose solution); a press on the other lever was followed by presentation of a larger reinforcer (four consecutive dipper presentations). The delay associated with the smaller reinforcer always was 0 s, whereas the signaled delay associated with the larger reinforcer increased across blocks (from 0 to 50 s). Under these conditions, the percentage of choices of the larger reinforcer decreased across blocks, and relatively reliable delay-discount functions were obtained within sessions. Doses of methylphenidate (1.0 to 17.0 mg/kg) and morphine (0.3 to 17.0 mg/kg) were then administered prior to selected sessions. Typically, intermediate doses of methylphenidate shifted the discount functions to the right (increased choices of the larger reinforcer). For 2 of the rats, this effect was pronounced; for the other 2 rats, this effect occurred after the range of delays for the larger reinforcer was decreased (0 to 20 s). On the other hand, in most cases morphine produced a slight leftward shift in the discount function (decreased choices of the larger reinforcer). The present procedure appears to be a useful and efficient method to characterize drug effects on an entire delay-discount function. As with many procedures used to study self-control choices, however, sources of control other than reinforcement delay and amount may have been operating in the present study, and these sources must be considered when interpreting drug effects. PMID:16047609
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The gearing function of running shoe longitudinal bending stiffness.
Willwacher, Steffen; König, Manuel; Braunstein, Björn; Goldmann, Jan-Peter; Brüggemann, Gert-Peter
2014-07-01
The purpose of the present study was to investigate whether altered longitudinal bending stiffness (LBS) levels of the midsole of a running shoe lead to a systematic change in lower extremity joint lever arms of the ground reaction force (GRF). Joint moments and GRF lever arms in the sagittal plane were determined from 19 male subjects running at 3.5 m/s using inverse dynamics procedures. LBS was manipulated using carbon fiber insoles of 1.9 mm and 3.2 mm thickness. Increasing LBS led to a significant shift of joint lever arms to a more anterior position. Effects were more pronounced at distal joints. Ankle joint moments were not significantly increased in the presence of higher GRF lever arms when averaged over all subjects. Still, two individual strategies (1: increase ankle joint moments while keeping push-off times almost constant, 2: decrease ankle joint moments and increase push-off times) could be identified in response to increased ankle joint lever arms that might reflect individual differences between subjects with respect to strength capacities or anthropometric characteristics. The results of the present study indicate that LBS systematically influences GRF lever arms of lower extremity joints during the push-off phase in running. Further, individual responses to altered LBS levels could be identified that could aid in finding optimum LBS values for a given individual. Copyright © 2014 Elsevier B.V. All rights reserved.
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Nemirovsky, Sergio I; Avale, M Elena; Brunner, Daniela; Rubinstein, Marcelo
2009-11-01
The dopamine D4 receptor (D4R) is predominantly expressed in the prefrontal cortex, a brain area that integrates motor, rewarding, and cognitive information. Because participation of D4Rs in executive learning is largely unknown, we challenged D4R knockout mice (Drd4(-/-)) and their wild-type (WT) littermates, neonatally treated with 6-hydroxydopamine (6-OHDA; icv) or vehicle in two operant learning paradigms. A continuous reinforcement task, in which one food-pellet was delivered after every lever press, showed that 6-OHDA-treated mice (hypodopaminergic) WT mice pressed the reinforcing lever at much lower rates than normodopaminergic WT mice. In contrast, Drd4(-/-) mice displayed increased lever pressing rates, regardless of their dopamine content. In another study, mice were trained to solve an operant two-choice task in which a first showing lever was coupled to the delivery of one food pellet only after a second lever emerged. Interval between presentation of both levers was initially 12 s and progressively shortened to 6, 2, and finally 0.5 s. Normodopaminergic WT mice obtained a pellet reward in more than 75% of the trials at 12, 6, and 2 s, whereas hypodopaminergic WT mice were severely impaired to select the reward-paired lever. Absence of D4Rs was not detrimental in this task. Moreover, hypodopaminergic Drd4(-/-) mice were as efficient as their normodopaminergic Drd4(-/-) siblings in selecting the reward-paired lever. In summary, hypodopaminergic mice exhibit severe impairments to retrieve rewards in two operant positive reinforcement tasks, but these deleterious effects are totally prevented in the absence of functional D4Rs.
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Lesion to the nigrostriatal dopamine system disrupts stimulus-response habit formation.
Faure, Alexis; Haberland, Ulrike; Condé, Françoise; El Massioui, Nicole
2005-03-16
Acquisition and performance of instrumental actions are assumed to require both action-outcome and stimulus-response (S-R) habit processes. Over the course of extended training, control over instrumental performance shifts from goal-directed action-outcome associations to S-R associations that progressively gain domination over behavior. Lesions of the lateral part of the dorsal striatum disrupt this process, and rats with lesions to the lateral striatum showed selective sensitivity to devaluation of the instrumental outcome (Yin et al., 2004), indicating that this area is necessary for habit formation. The present experiment further explored the basis of this dysfunction by examining the ability of rats subjected to bilateral 6-hydroxydopamine lesions of the nigrostriatal dopaminergic pathway to develop behavioral autonomy with overtraining. Rats were given extended training on two cued instrumental tasks associating a stimulus (a tone or a light) with an instrumental action (lever press or chain pull) and a food reward (pellets or sucrose). Both tasks were run daily in separate sessions. Overtraining was followed by a test of goal sensitivity by satiety-specific devaluation of the reward. In control animals, one action (lever press) was insensitive to reward devaluation, indicating that it became a habit, whereas the second action (chain pull) was still sensitive to goal devaluation. This result provides evidence that the development of habit learning may depend on the characteristics of the response. In dopamine-depleted rats, lever press and chain pull remained sensitive to reward devaluation, evidencing a role of striatal dopamine transmission in habit formation.
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Remote sensing of liquid level measurement using Fiber Bragg grating sensor
NASA Astrophysics Data System (ADS)
Sengupta, Dipankar; Shankar, M. Sai; Srimannarayana, K.; Vengal Rao, P.
2013-09-01
The present work proposes a simple low cost sensor head design making use of FBG sensor, for the measurement of liquid level. The sensor head consists of a lever, a buoyancy tube and an FBG. The lever is used to transfer the buoyancy force due to change in liquid level to the FBG resulting in shift in Bragg wavelength. The Flexibility of this design enables to measure the liquid level in an open or closed tank. The arrangement shows that liquid level sensitivity is high and is 10.7pm/mm.
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Tunstall, Brendan J.; Kearns, David N.
2013-01-01
Recent studies (for review see Ahmed, 2010; 2012) show that when given a mutually exclusive choice between cocaine and food, rats almost exclusively choose food. The present experiment investigated potential shifts in preference between levers associated with either food or cocaine which might occur during extinction (food and cocaine no longer available) and during footshock-induced, cocaine-primed, and food-primed reinstatement. During self-administration sessions where food and cocaine were simultaneously available, rats demonstrated a stable food preference, choosing food over cocaine on 83% of trials. During extinction when neither reinforcer was available, no preference between levers was evident and responding decreased until rats responded on the previously food- and cocaine-associated levers at equally low rates. Footshock resulted in a non-specific reinstatement of responding upon both levers, while cocaine priming resulted in a significant preference for cocaine seeking over food seeking. This suggests that the mechanism underlying footshock-induced reinstatement is distinct from that of cocaine-primed reinstatement. Food priming engendered a mild, non-specific increase in responding on both levers. Although rats generally prefer food over cocaine when presented with a choice between these primary reinforcers, the present results suggest that in certain situations cocaine-seeking behavior prevails over food-seeking behavior. PMID:23551949
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Sex and Adolescent Ethanol Exposure Influence Pavlovian Conditioned Approach
Madayag, Aric C.; Stringfield, Sierra J.; Reissner, Kathryn J.; Boettiger, Charlotte A.; Robinson, Donita L.
2017-01-01
BACKGROUND Alcohol use among adolescents is widespread and a growing concern due to long-term behavioral deficits, including altered Pavlovian behavior, that potentially contribute to addiction vulnerability. We tested the hypothesis that adolescent intermittent ethanol (AIE) exposure alters Pavlovian behavior in males and females as measured by a shift from goal-tracking to sign-tracking. Additionally, we investigated GLT-1, an astrocytic glutamate transporter, as a potential contributor to a sign-tracking phenotype. METHODS Male and female Sprague-Dawley rats were exposed to AIE (5g/Kg, intragastric) or water intermittently 2 days on, 2 days off from postnatal day (P) 25 to 54. Around P70, animals began 20 daily sessions of Pavlovian conditioned approach, where they learned that a cue predicted non-contingent reward delivery. Lever pressing indicated interaction with the cue, or sign-tracking, and receptacle entries indicated approach to the reward delivery location, or goal-tracking. To test for effects of AIE on nucleus accumbens excitatory signaling, we isolated membrane subfractions and measured protein levels of the glutamate transporter GLT-1 after animals completed behavior as a measure of glutamate homeostasis. RESULTS Females exhibited elevated sign-tracking compared to males with significantly more lever presses, faster latency to first lever press, and greater probability to lever press in a trial. AIE significantly increased lever pressing while blunting goal tracking, as indicated by fewer cue-evoked receptacle entries, slower latency to receptacle entry, and lower probability to enter the receptacle in a trial. No significant Sex-by-Exposure interactions were observed in sign- or goal-tracking metrics. Moreover, we found no significant effects of Sex or Exposure on membrane GLT-1 expression in the nucleus accumbens. CONCLUSIONS Females exhibited enhanced sign-tracking compared to males, while AIE decreased goal-tracking compared to control exposure. Our findings support the hypothesis that adolescent binge ethanol can shift conditioned behavior from goal- to cue-directed in Pavlovian conditioned approach, especially in females. PMID:28196273
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Sex and Adolescent Ethanol Exposure Influence Pavlovian Conditioned Approach.
Madayag, Aric C; Stringfield, Sierra J; Reissner, Kathryn J; Boettiger, Charlotte A; Robinson, Donita L
2017-04-01
Alcohol use among adolescents is widespread and a growing concern due to long-term behavioral deficits, including altered Pavlovian behavior, that potentially contribute to addiction vulnerability. We tested the hypothesis that adolescent intermittent ethanol (AIE) exposure alters Pavlovian behavior in males and females as measured by a shift from goal-tracking to sign-tracking. Additionally, we investigated GLT-1, an astrocytic glutamate transporter, as a potential contributor to a sign-tracking phenotype. Male and female Sprague-Dawley rats were exposed to AIE (5 g/kg, intragastric) or water intermittently 2 days on and 2 days off from postnatal day (P) 25 to 54. Around P70, animals began 20 daily sessions of Pavlovian conditioned approach (PCA), where they learned that a cue predicted noncontingent reward delivery. Lever pressing indicated interaction with the cue, or sign-tracking, and receptacle entries indicated approach to the reward delivery location, or goal-tracking. To test for effects of AIE on nucleus accumbens (NAcc) excitatory signaling, we isolated membrane subfractions and measured protein levels of the glutamate transporter GLT-1 after animals completed behavior as a measure of glutamate homeostasis. Females exhibited elevated sign-tracking compared to males with significantly more lever presses, faster latency to first lever press, and greater probability to lever press in a trial. AIE significantly increased lever pressing while blunting goal-tracking, as indicated by fewer cue-evoked receptacle entries, slower latency to receptacle entry, and lower probability to enter the receptacle in a trial. No significant sex-by-exposure interactions were observed in sign- or goal-tracking metrics. Moreover, we found no significant effects of sex or exposure on membrane GLT-1 expression in the NAcc. Females exhibited enhanced sign-tracking compared to males, while AIE decreased goal-tracking compared to control exposure. Our findings support the hypothesis that adolescent binge ethanol can shift conditioned behavior from goal- to cue-directed in PCA, especially in females. Copyright © 2017 by the Research Society on Alcoholism.
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Belke, Terry W; Pierce, W David
2016-12-01
Rats responded on a multiple variable-ratio (VR) 10 VR 10 schedule of reinforcement in which lever pressing was reinforced by the opportunity to run in a wheel for 30s in both the changed (manipulated) and unchanged components. To generate positive contrast, the schedule of reinforcement in the changed component was shifted to extinction; to generate negative contrast, the schedule was shifted to VR 3. With the shift to extinction in the changed component, wheel-running and local lever-pressing rates increased in the unchanged component, a result supporting positive contrast; however, the shift to a VR 3 schedule in the changed component showed no evidence of negative contrast in the unaltered setting, only wheel running decreased in the unchanged component. Changes in wheel-running rates across components were consistent in showing a compensation effect, depending on whether the schedule manipulation increased or decreased opportunities for wheel running in the changed component. These findings are the first to demonstrate positive behavioral contrast on a multiple schedule with wheel running as reinforcement in both components. Copyright © 2016 Elsevier B.V. All rights reserved.
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Policy for material efficiency--sustainable taxation as a departure from the throwaway society.
Stahel, Walter R
2013-03-13
The present economy is not sustainable with regard to its per capita material consumption. A dematerialization of the economy of industrialized countries can be achieved by a change in course, from an industrial economy built on throughput to a circular economy built on stock optimization, decoupling wealth and welfare from resource consumption while creating more work. The business models of a circular economy have been known since the mid-1970s and are now applied in a number of industrial sectors. This paper argues that a simple and convincing lever could accelerate the shift to a circular economy, and that this lever is the shift to a tax system based on the principles of sustainability: not taxing renewable resources including human labour--work--but taxing non-renewable resources instead is a powerful lever. Taxing materials and energies will promote low-carbon and low-resource solutions and a move towards a 'circular' regional economy as opposed to the 'linear' global economy requiring fuel-based transport for goods throughput. In addition to substantial improvements in material and energy efficiency, regional job creation and national greenhouse gas emission reductions, such a change will foster all activities based on 'caring', such as maintaining cultural heritage and natural wealth, health services, knowledge and know-how.
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Contreras-Mora, Hector; Rowland, Margaret A; Yohn, Samantha E; Correa, Merce; Salamone, John D
2018-03-01
People with depression and Parkinsonism frequently show effort-related motivational symptoms, such as anergia, psychomotor retardation, and fatigue. Tasks that assess effort-related choice are being used as animal models of these motivational symptoms. The present studies characterized the ability of monoamine oxidase (MAO) inhibitors with varying selectivity profiles to reverse the low effort bias induced by the monoamine storage inhibitor tetrabenazine. Tetrabenazine produces depressive symptoms in humans, and because of its selective inhibition of VMAT-2, it preferentially depletes DA at low doses. Effort-based decision making is studied with tasks offering choices between high effort options leading to highly valued reinforcers vs. low effort/low reward options. Tetrabenazine shifted choice behavior, reducing selection of fixed ratio 5 lever pressing, but increasing intake of the concurrently available but less preferred lab chow. These effects of 0.75mg/kg tetrabenazine were attenuated by co-administration of the MAO-B inhibitor deprenyl (selegiline). The ability of deprenyl to reverse the effects of tetrabenazine was marked by an inverted-U shaped dose response curve, with the middle dose (2.5mg/kg) being effective. In contrast, neither the MAO-A selective antagonist moclobemide nor the nonselective drug pargyline reversed the effects of tetrabenazine, and moclobemide decreased lever pressing when administered alone. Deprenyl was originally developed as an antiparkinsonian drug, but it also has been shown to have antidepressant effects in humans and induce antidepressant-like effects in classical rodent models of depression. These studies have implications for the potential use of MAO-B inhibitors as treatments for the motivational symptoms of depression and Parkinsonism. Copyright © 2017. Published by Elsevier Inc.
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Single cardiac ventricular myosins are autonomous motors
Wang, Yihua; Yuan, Chen-Ching; Kazmierczak, Katarzyna; Szczesna-Cordary, Danuta
2018-01-01
Myosin transduces ATP free energy into mechanical work in muscle. Cardiac muscle has dynamically wide-ranging power demands on the motor as the muscle changes modes in a heartbeat from relaxation, via auxotonic shortening, to isometric contraction. The cardiac power output modulation mechanism is explored in vitro by assessing single cardiac myosin step-size selection versus load. Transgenic mice express human ventricular essential light chain (ELC) in wild- type (WT), or hypertrophic cardiomyopathy-linked mutant forms, A57G or E143K, in a background of mouse α-cardiac myosin heavy chain. Ensemble motility and single myosin mechanical characteristics are consistent with an A57G that impairs ELC N-terminus actin binding and an E143K that impairs lever-arm stability, while both species down-shift average step-size with increasing load. Cardiac myosin in vivo down-shifts velocity/force ratio with increasing load by changed unitary step-size selections. Here, the loaded in vitro single myosin assay indicates quantitative complementarity with the in vivo mechanism. Both have two embedded regulatory transitions, one inhibiting ADP release and a second novel mechanism inhibiting actin detachment via strain on the actin-bound ELC N-terminus. Competing regulators filter unitary step-size selection to control force-velocity modulation without myosin integration into muscle. Cardiac myosin is muscle in a molecule. PMID:29669825
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PUNISHING AND CARDIOVASCULAR EFFECTS OF INTRAVENOUS HISTAMINE IN RATS: PHARMACOLOGICAL SELECTIVITY
Podlesnik, Christopher A.; Jimenez-Gomez, Corina
2014-01-01
Although drugs may serve as reinforcers or punishers of operant behavior, the punishing function has received much less experimental attention than the reinforcing function. A sensitive method for studying drug-induced punishment is to assess choice for a punished response over an unpunished response. In these experiments, rats chose between pressing one lever and receiving a sucrose pellet or pressing another lever and receiving a sucrose pellet plus an intravenous injection of histamine. When sucrose was delivered equally frequently for either the punished or the unpunished response, rats selected the unpunished lever consistently, but decreases in the punished response did not differ as a function of intravenous histamine dose (0.1–1 mg/kg/inj). Changing the procedure so that sucrose was delivered on the unpunished lever with p = .5 increased the rats’ responding on the punished lever with saline injections. In addition, the same range of histamine doses produced a much larger range of responses on the punished lever that was dose dependent. Using these procedures to assess the receptors mediating histamine’s effects, the histamine H1-receptor antagonists, pyrilamine and ketotifen, antagonized the punishing effect of histamine, but the histamine H2-receptor antagonist ranitidine did not. However, ranitidine pretreatments reduced histamine-induced heart-rate increases to a greater extent than did the histamine H1-receptor antagonists when administered at the same doses examined under conditions of histamine punishment. Overall, the present findings extend the general hypothesis that activation of histamine H1-receptors mediates the punishing effects of histamine. They also introduce methods for rapidly assessing pharmacological mechanisms underlying drug-induced punishment. PMID:23982898
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CHARACTERIZATION OF THE DISCRIMINATIVE STIMULUS EFFECTS OF LORCASERIN IN RATS
Serafine, Katherine M.; Rice, Kenner C.; France, Charles P.
2016-01-01
Lorcaserin is approved by the Food and Drug Administration for treating obesity and is under consideration for treating substance use disorders; it has agonist properties at serotonin (5-HT)2C receptors and might also have agonist properties at other 5-HT receptor subtypes. This study used drug discrimination to investigate the mechanism(s) of action of lorcaserin. Male Sprague-Dawley rats discriminated 0.56 mg/kg i.p. lorcaserin from saline while responding under a fixed-ratio 5 schedule for food. Lorcaserin (0.178–1.0 mg/kg) dose-dependently increased lorcaserin-lever responding. The 5-HT2C receptor agonist mCPP and the 5-HT2A receptor agonist DOM each occasioned greater than 90% lorcaserin-lever responding in seven of eight rats. The 5-HT1A receptor agonist 8-OH-DPAT occasioned greater than 90% lorcaserin-lever responding in four of seven rats. The 5-HT2C receptor selective antagonist SB 242084 attenuated lorcaserin-lever responding in all eight rats and the 5-HT2A receptor selective antagonist MDL 100907 attenuated lorcaserin-lever responding in six of seven rats. These results suggest that, in addition to agonist properties at 5-HT2C receptors, lorcaserin also has agonist properties at 5-HT2A and 5-HT1A receptors. Because some drugs with 5-HT2A receptor agonist properties are abused, it is important to fully understand the behavioral effects of lorcaserin while considering its potential for treating substance use disorders. PMID:27640338
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Teacher Networks in Philadelphia: Landscape, Engagement, and Value
ERIC Educational Resources Information Center
Schiff, Daniel; Herzog, Liza; Farley-Ripple, Elizabeth; Iannuccilli, Lauren Thum
2015-01-01
Teacher collaboration has become an increasingly important lever for school improvement efforts. This is especially true in high need urban districts, which struggle with capacity building in the face of significant teacher turnover, major shifts in curriculum and instruction, and scarce resources. This paper employs a mixed methods approach to…
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Expanding Instructional Horizons: A Case Study of Teacher Team-Outside Expert Partnerships
ERIC Educational Resources Information Center
Ermeling, Bradley A.; Yarbo, Jessica
2016-01-01
Background: Despite increasing popularity and mounting evidence for teacher collaboration as a lever for school improvement, reported changes in teaching associated with collaboration are often subtle and incremental, rarely involving substantial shifts in instructional practice called for by advocates of deeper learning and next-generation…
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Stinson, W.J.
1958-09-16
A valve designed to selectively sample fluids from a number of sources is described. The valve comprises a rotatable operating lever connected through a bellows seal to a rotatable assembly containing a needle valve, bearings, and a rotational lock. The needle valve is connected through a flexible tube to the sample fluid outlet. By rotating the lever the needle valve is placed over . one of several fluid sources and locked in position so that the fluid is traasferred through the flexible tubing and outlet to a remote sampling system. The fluids from the nonselected sources are exhausted to a waste line. This valve constitutes a simple, dependable means of selecting a sample from one of several scurces.
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Nett, Kelle E.; Cosme, Caitlin V.; Worth, Wensday R.; Wemmie, John A.
2017-01-01
The infralimbic cortex (IL) mediates extinction learning and the active suppression of cocaine-seeking behavior. However, the precise temporal relationship among IL activity, lever pressing, and extinction learning is unclear. To address this issue, we used activity-guided optogenetics in male Sprague Dawley rats to silence IL pyramidal neurons optically for 20 s immediately after unreinforced lever presses during early extinction training after cocaine self-administration. Optical inhibition of the IL increased active lever pressing during shortened extinction sessions, but did not alter the retention of the extinction learning as assessed in ensuing extinction sessions with no optical inhibition. During subsequent cued reinstatement sessions, rats that had previously received optical inhibition during the extinction sessions showed increased cocaine-seeking behavior. These findings appeared to be specific to inhibition during the post-lever press period because IL inhibition given in a noncontingent, pseudorandom manner during extinction sessions did not produce the same effects. Illumination alone (i.e., with no opsin expression) and food-seeking control experiments also failed to produce the same effects. In another experiment, IL inhibition after lever presses during cued reinstatement sessions increased cocaine seeking during those sessions. Finally, inhibition of the prelimbic cortex immediately after unreinforced lever presses during shortened extinction sessions decreased lever pressing during these sessions, but had no effect on subsequent reinstatement. These results indicate that IL activity immediately after unreinforced lever presses is necessary for normal extinction of cocaine seeking, suggesting that critical encoding of the new contingencies between a lever press and a cocaine reward occurs during that period. SIGNIFICANCE STATEMENT The infralimbic cortex (IL) contributes to the extinction of cocaine-seeking behavior, but the precise relationship among IL activity, lever pressing during extinction, and extinction learning has not been elucidated using traditional methods. Using a closed-loop optogenetic approach, we found that selective inhibition of the IL immediately after unreinforced lever pressing impaired within-session extinction learning and promoted the subsequent cued reinstatement of cocaine seeking. These studies suggest that IL activity immediately after the instrumental response during extinction learning of cocaine seeking encodes information required for such learning and that altering such activity produces long-lasting changes in subsequent measures of cocaine craving/relapse. PMID:28539416
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Gutman, Andrea L; Nett, Kelle E; Cosme, Caitlin V; Worth, Wensday R; Gupta, Subhash C; Wemmie, John A; LaLumiere, Ryan T
2017-06-21
The infralimbic cortex (IL) mediates extinction learning and the active suppression of cocaine-seeking behavior. However, the precise temporal relationship among IL activity, lever pressing, and extinction learning is unclear. To address this issue, we used activity-guided optogenetics in male Sprague Dawley rats to silence IL pyramidal neurons optically for 20 s immediately after unreinforced lever presses during early extinction training after cocaine self-administration. Optical inhibition of the IL increased active lever pressing during shortened extinction sessions, but did not alter the retention of the extinction learning as assessed in ensuing extinction sessions with no optical inhibition. During subsequent cued reinstatement sessions, rats that had previously received optical inhibition during the extinction sessions showed increased cocaine-seeking behavior. These findings appeared to be specific to inhibition during the post-lever press period because IL inhibition given in a noncontingent, pseudorandom manner during extinction sessions did not produce the same effects. Illumination alone (i.e., with no opsin expression) and food-seeking control experiments also failed to produce the same effects. In another experiment, IL inhibition after lever presses during cued reinstatement sessions increased cocaine seeking during those sessions. Finally, inhibition of the prelimbic cortex immediately after unreinforced lever presses during shortened extinction sessions decreased lever pressing during these sessions, but had no effect on subsequent reinstatement. These results indicate that IL activity immediately after unreinforced lever presses is necessary for normal extinction of cocaine seeking, suggesting that critical encoding of the new contingencies between a lever press and a cocaine reward occurs during that period. SIGNIFICANCE STATEMENT The infralimbic cortex (IL) contributes to the extinction of cocaine-seeking behavior, but the precise relationship among IL activity, lever pressing during extinction, and extinction learning has not been elucidated using traditional methods. Using a closed-loop optogenetic approach, we found that selective inhibition of the IL immediately after unreinforced lever pressing impaired within-session extinction learning and promoted the subsequent cued reinstatement of cocaine seeking. These studies suggest that IL activity immediately after the instrumental response during extinction learning of cocaine seeking encodes information required for such learning and that altering such activity produces long-lasting changes in subsequent measures of cocaine craving/relapse. Copyright © 2017 the authors 0270-6474/17/376075-12$15.00/0.
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Evenden, John
2002-10-01
Psychosis and psychotomimetic drugs result in a disorganisation of the structure of thought and behaviour. Normalising these is one of the objects of antipsychotic therapy, and methods for predicting such a therapeutic effect would be of value. The effects of a number of psychotomimetic agents were examined on the way in which rats distributed responding over two response levers using two different procedures, to assay their effects on behavioural organisation. Previously, amphetamine has been found to increase response switching using these schedules. In the first, the random reinforcement procedure, one of the two levers was selected at random as "correct", and responses on this lever were reinforced with food under a random ratio schedule. No signal was given to distinguish the levers. Responding could also result in the food tray being illuminated, but no food pellet was delivered ("no-food" event). Responses on the second lever ("incorrect") had no programmed consequences. After each food delivery or "no-food" event the levers designated as "correct" and "incorrect" were reassigned at random, and the rat had to open the food tray to restart the schedule. In the second procedure, the rats were required to make 21 responses before a switch between the two levers resulted in food delivery [Fixed Ratio (FR) 21-switch]. The responses making up the FR could be distributed freely between the two levers. Phencyclidine (PCP), scopolamine, caffeine and ethanol increased switching under the random reinforcement procedure, but (+/-)-2,5-dimethoxy-4-iodoamphetamine hydrochloride (DOI) and atropine did not. PCP, caffeine, lysergic acid diethylamide (LSD) and atropine increased switching under the FR21-switch procedure, but ethanol did not. The increases in switching produced by PCP, LSD and the anticholinergics were accompanied by marked reductions in response rate, whereas those produced by amphetamine and caffeine were not. The effects of amphetamine, and PCP were strongly dependent on the baseline probability of switching, those of atropine and caffeine moderately so, and those of LSD and ethanol only weakly so. Of the agents tested, psychomotor stimulants appear to produce the most selective increases in switching. The procedures described here may be useful for assaying the disorganisation of behaviour produced by other psychotomimetics and may have value in the detection of novel antipsychotic drugs.
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Characterization of the discriminative stimulus effects of lorcaserin in rats.
Serafine, Katherine M; Rice, Kenner C; France, Charles P
2016-09-01
Lorcaserin is approved by the Food and Drug Administration for treating obesity and is under consideration for treating substance use disorders; it has agonist properties at serotonin (5-HT)2C receptors and might also have agonist properties at other 5-HT receptor subtypes. This study used drug discrimination to investigate the mechanism(s) of action of lorcaserin. Male Sprague-Dawley rats discriminated 0.56 mg/kg i.p. lorcaserin from saline while responding under a fixed-ratio 5 schedule for food. Lorcaserin (0.178-1.0 mg/kg) dose-dependently increased lorcaserin-lever responding. The 5-HT2C receptor agonist mCPP and the 5-HT2A receptor agonist DOM each occasioned greater than 90% lorcaserin-lever responding in seven of eight rats. The 5-HT1A receptor agonist 8-OH-DPAT occasioned greater than 90% lorcaserin-lever responding in four of seven rats. The 5-HT2C receptor selective antagonist SB 242084 attenuated lorcaserin-lever responding in all eight rats and the 5-HT2A receptor selective antagonist MDL 100907 attenuated lorcaserin-lever responding in six of seven rats. These results suggest that, in addition to agonist properties at 5-HT2C receptors, lorcaserin also has agonist properties at 5-HT2A and 5-HT1A receptors. Because some drugs with 5-HT2A receptor agonist properties are abused, it is important to fully characterize the behavioral effects of lorcaserin while considering its potential for treating substance use disorders. © 2016 Society for the Experimental Analysis of Behavior.
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Changing Relations between Learning and Work
ERIC Educational Resources Information Center
Jefferson, Anne L.; Levitan, Barbara
2006-01-01
The change in technology, in communications and in the dynamics of human and institutional interactions has created a need to shift relations between the world of learning and the world of work. New levers need to be added to those currently relied on. Consequently the learning-work relationship that exists between tertiary education institutions…
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Designing and Implementing Human Capital Management Systems in Educator Evaluation
ERIC Educational Resources Information Center
Kraemer, Sara; Milanowski, Anthony; Scott, Jenna; Adrien, Richard; Fairbairn, Shane; Bourn, Ronda; Hill, Marsha
2015-01-01
The Department of Education's Teacher Incentive Fund (TIF) 4 program represents a programmatic shift away from educator compensation reform as the primary lever of change for teacher performance and student learning. The TIF 4 program is designed to encourage the use of educator effectiveness measures to support the strategic instructional vision…
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Grace, Francesca C; Meurk, Carla S; Head, Brian W; Hall, Wayne D; Harris, Meredith G; Whiteford, Harvey A
2017-05-30
Heightened fiscal constraints, increases in the chronic disease burden and in consumer expectations are among several factors contributing to the global interest in evidence-informed health policy. The present article builds on previous work that explored how the Australian Federal Government applied five instruments of policy, or policy levers, to implement a series of reforms under the Australian National Mental Health Strategy (NMHS). The present article draws on theoretical insights from political science to analyse the relative successes and failures of these levers, as portrayed in formal government evaluations of the NMHS. Documentary analysis of six evaluation documents corresponding to three National Mental Health Plans was undertaken. Both the content and approach of these government-funded, independently conducted evaluations were appraised. An overall improvement was apparent in the development and application of policy levers over time. However, this finding should be interpreted with caution due to variations in evaluation approach according to Plan and policy lever. Tabulated summaries of the success and failure of each policy initiative, ordered by lever type, are provided to establish a resource that could be consulted for future policy-making. This analysis highlights the complexities of health service reform and underscores the limitations of narrowly focused empirical approaches. A theoretical framework is provided that could inform the evaluation and targeted selection of appropriate policy levers in mental health.
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Srey, Chandra S; Maddux, Jean-Marie N; Chaudhri, Nadia
2015-01-01
Environmental stimuli that are reliably paired with alcohol may acquire incentive salience, a property that can operate in the use and abuse of alcohol. Here we investigated the incentive salience of Pavlovian alcohol cues using a preclinical animal model. Male, Long-Evans rats (Harlan) with unrestricted access to food and water were acclimated to drinking 15% ethanol (v/v) in their home-cages. Rats then received Pavlovian autoshaping training in which the 10 s presentation of a retractable lever served as the conditioned stimulus (CS) and 15% ethanol served as the unconditioned stimulus (US) (0.2 ml/CS; 12 CS presentations/session; 27 sessions). Next, in an operant test of conditioned reinforcement, nose pokes into an active aperture delivered presentations of the lever-CS, whereas nose pokes into an inactive aperture had no consequences. Across initial autoshaping sessions, goal-tracking behavior, as measured by entries into the fluid port where ethanol was delivered, developed rapidly. However, with extended training goal-tracking diminished, and sign-tracking responses, as measured by lever-CS activations, emerged. Control rats that received explicitly unpaired CS and US presentations did not show goal-tracking or sign-tracking responses. In the test for conditioned reinforcement, rats with CS-US pairings during autoshaping training made more active relative to inactive nose pokes, whereas rats in the unpaired control group did not. Moreover, active nose pokes were positively correlated with sign-tracking behavior during autoshaping. Extended training may produce a shift in the learned properties of Pavlovian alcohol cues, such that after initially predicting alcohol availability they acquire robust incentive salience.
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O'Hare, Justin K; Li, Haofang; Kim, Namsoo; Gaidis, Erin; Ade, Kristen; Beck, Jeff; Yin, Henry
2017-01-01
Habit formation is a behavioral adaptation that automates routine actions. Habitual behavior correlates with broad reconfigurations of dorsolateral striatal (DLS) circuit properties that increase gain and shift pathway timing. The mechanism(s) for these circuit adaptations are unknown and could be responsible for habitual behavior. Here we find that a single class of interneuron, fast-spiking interneurons (FSIs), modulates all of these habit-predictive properties. Consistent with a role in habits, FSIs are more excitable in habitual mice compared to goal-directed and acute chemogenetic inhibition of FSIs in DLS prevents the expression of habitual lever pressing. In vivo recordings further reveal a previously unappreciated selective modulation of SPNs based on their firing patterns; FSIs inhibit most SPNs but paradoxically promote the activity of a subset displaying high fractions of gamma-frequency spiking. These results establish a microcircuit mechanism for habits and provide a new example of how interneurons mediate experience-dependent behavior. PMID:28871960
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Regulatory light chain mutants linked to heart disease modify the cardiac myosin lever arm.
Burghardt, Thomas P; Sikkink, Laura A
2013-02-19
Myosin is the chemomechanical energy transducer in striated heart muscle. The myosin cross-bridge applies impulsive force to actin while consuming ATP chemical energy to propel myosin thick filaments relative to actin thin filaments in the fiber. Transduction begins with ATP hydrolysis in the cross-bridge driving rotary movement of a lever arm converting torque into linear displacement. Myosin regulatory light chain (RLC) binds to the lever arm and modifies its ability to translate actin. Gene sequencing implicated several RLC mutations in heart disease, and three of them are investigated here using photoactivatable GFP-tagged RLC (RLC-PAGFP) exchanged into permeabilized papillary muscle fibers. A single-lever arm probe orientation is detected in the crowded environment of the muscle fiber by using RLC-PAGFP with dipole orientation deduced from the three-spatial dimension fluorescence emission pattern of the single molecule. Symmetry and selection rules locate dipoles in their half-sarcomere, identify those at the minimal free energy, and specify active dipole contraction intermediates. Experiments were performed in a microfluidic chamber designed for isometric contraction, total internal reflection fluorescence detection, and two-photon excitation second harmonic generation to evaluate sarcomere length. The RLC-PAGFP reports apparently discretized lever arm orientation intermediates in active isometric fibers that on average produce the stall force. Disease-linked mutants introduced into RLC move intermediate occupancy further down the free energy gradient, implying lever arms rotate more to reach stall force because mutant RLC increases lever arm shear strain. A lower free energy intermediate occupancy involves a lower energy conversion efficiency in the fiber relating a specific myosin function modification to the disease-implicated mutant.
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Randall, Patrick A.; Lee, Christie A.; Nunes, Eric J.; Yohn, Samantha E.; Nowak, Victoria; Khan, Bilal; Shah, Priya; Pandit, Saagar; Vemuri, V. Kiran; Makriyannis, Alex; Baqi, Younis; Müller, Christa E.; Correa, Merce; Salamone, John D.
2014-01-01
Behavioral activation is a fundamental feature of motivation, and organisms frequently make effort-related decisions based upon evaluations of reinforcement value and response costs. Furthermore, people with major depression and other disorders often show anergia, psychomotor retardation, fatigue, and alterations in effort-related decision making. Tasks measuring effort-based decision making can be used as animal models of the motivational symptoms of depression, and the present studies characterized the effort-related effects of the vesicular monoamine transport (VMAT-2) inhibitor tetrabenazine. Tetrabenazine induces depressive symptoms in humans, and also preferentially depletes dopamine (DA). Rats were assessed using a concurrent progressive ratio (PROG)/chow feeding task, in which they can either lever press on a PROG schedule for preferred high-carbohydrate food, or approach and consume a less-preferred lab chow that is freely available in the chamber. Previous work has shown that the DA antagonist haloperidol reduced PROG work output on this task, but did not reduce chow intake, effects that differed substantially from those of reinforcer devaluation or appetite suppressant drugs. The present work demonstrated that tetrabenazine produced an effort-related shift in responding on the PROG/chow procedure, reducing lever presses, highest ratio achieved and time spent responding, but not reducing chow intake. Similar effects were produced by administration of the subtype selective DA antagonists ecopipam (D1) and eticlopride (D2), but not by the cannabinoid CB1 receptor neutral antagonist and putative appetite suppressant AM 4413, which suppressed both lever pressing and chow intake. The adenosine A2A antagonist MSX-3, the antidepressant and catecholamine uptake inhibitor bupropion, and the MAO-B inhibitor deprenyl, all reversed the impairments induced by tetrabenazine. This work demonstrates the potential utility of the PROG/chow procedure as a rodent model of the effort-related deficits observed in depressed patients. PMID:24937131
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Randall, Patrick A; Lee, Christie A; Nunes, Eric J; Yohn, Samantha E; Nowak, Victoria; Khan, Bilal; Shah, Priya; Pandit, Saagar; Vemuri, V Kiran; Makriyannis, Alex; Baqi, Younis; Müller, Christa E; Correa, Merce; Salamone, John D
2014-01-01
Behavioral activation is a fundamental feature of motivation, and organisms frequently make effort-related decisions based upon evaluations of reinforcement value and response costs. Furthermore, people with major depression and other disorders often show anergia, psychomotor retardation, fatigue, and alterations in effort-related decision making. Tasks measuring effort-based decision making can be used as animal models of the motivational symptoms of depression, and the present studies characterized the effort-related effects of the vesicular monoamine transport (VMAT-2) inhibitor tetrabenazine. Tetrabenazine induces depressive symptoms in humans, and also preferentially depletes dopamine (DA). Rats were assessed using a concurrent progressive ratio (PROG)/chow feeding task, in which they can either lever press on a PROG schedule for preferred high-carbohydrate food, or approach and consume a less-preferred lab chow that is freely available in the chamber. Previous work has shown that the DA antagonist haloperidol reduced PROG work output on this task, but did not reduce chow intake, effects that differed substantially from those of reinforcer devaluation or appetite suppressant drugs. The present work demonstrated that tetrabenazine produced an effort-related shift in responding on the PROG/chow procedure, reducing lever presses, highest ratio achieved and time spent responding, but not reducing chow intake. Similar effects were produced by administration of the subtype selective DA antagonists ecopipam (D1) and eticlopride (D2), but not by the cannabinoid CB1 receptor neutral antagonist and putative appetite suppressant AM 4413, which suppressed both lever pressing and chow intake. The adenosine A2A antagonist MSX-3, the antidepressant and catecholamine uptake inhibitor bupropion, and the MAO-B inhibitor deprenyl, all reversed the impairments induced by tetrabenazine. This work demonstrates the potential utility of the PROG/chow procedure as a rodent model of the effort-related deficits observed in depressed patients.
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Consequential Validity and the Transformation of Tests from Measurement Tools to Policy Tools
ERIC Educational Resources Information Center
Welner, Kevin G.
2013-01-01
Background/Context: Recent U.S. policy has brought a shift in assessment use, from measurement tools to policy levers. In particular, testing has become a core part of teacher evaluation policies in many states, with test results becoming akin to a job evaluation. Purpose: To explore the notion of consequential validity in assessment use and…
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The Case for a Paradigm Shift in Extension from Information-Centric to Community-Centric Programming
ERIC Educational Resources Information Center
Strong, Emma; Rowntree, Jason; Thurlow, Kable; Raven, Matt R.
2015-01-01
Since its establishment through the Smith-Lever Act, the Cooperative Extension Service has sought to use non-formal education programs centered on community needs to provide research-based information. However, the onset of the information age has transformed the way knowledge is shared and as a result altered the way people access information.…
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Randall, Patrick A.; Nunes, Eric J.; Janniere, Simone L.; Stopper, Colin M.; Farrar, Andrew M.; Sager, Thomas N.; Baqi, Younis; Hockemeyer, Jörg; Müller, Christa E.
2012-01-01
Rationale Adenosine A2A antagonists can reverse many of the behavioral effects of dopamine antagonists, including actions on instrumental behavior. However, little is known about the effects of selective adenosine antagonists on operant behavior when these drugs are administered alone. Objective The present studies were undertaken to investigate the potential for rate-dependent stimulant effects of both selective and nonselective adenosine antagonists. Methods Six drugs were tested: two nonselective adenosine antagonists (caffeine and theophylline), two adenosine A1 antagonists (DPCPX and CPT), and two adenosine A2A antagonists (istradefylline (KW6002) and MSX-3). Two schedules of reinforcement were employed; a fixed interval 240-s (FI-240 sec) schedule was used to generate low baseline rates of responding and a fixed ratio 20 (FR20) schedule generated high rates. Results Caffeine and theophylline produced rate-dependent effects on lever pressing, increasing responding on the FI-240 sec schedule but decreasing responding on the FR20 schedule. The A2A antagonists MSX-3 and istradefylline increased FI-240 sec lever pressing but did not suppress FR20 lever pressing in the dose range tested. In fact, there was a tendency for istradefylline to increase FR20 responding at a moderate dose. A1 antagonists failed to increase lever pressing rate, but DPCPX decreased FR20 responding at higher doses. Conclusions These results suggest that adenosine A2A antagonists enhance operant response rates, but A1 antagonists do not. The involvement of adenosine A2A receptors in regulating aspects of instrumental response output and behavioral activation may have implications for the treatment of effort-related psychiatric dysfunctions, such as psychomotor slowing and anergia in depression. PMID:21347642
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Srey, Chandra S.; Maddux, Jean-Marie N.; Chaudhri, Nadia
2015-01-01
Environmental stimuli that are reliably paired with alcohol may acquire incentive salience, a property that can operate in the use and abuse of alcohol. Here we investigated the incentive salience of Pavlovian alcohol cues using a preclinical animal model. Male, Long-Evans rats (Harlan) with unrestricted access to food and water were acclimated to drinking 15% ethanol (v/v) in their home-cages. Rats then received Pavlovian autoshaping training in which the 10 s presentation of a retractable lever served as the conditioned stimulus (CS) and 15% ethanol served as the unconditioned stimulus (US) (0.2 ml/CS; 12 CS presentations/session; 27 sessions). Next, in an operant test of conditioned reinforcement, nose pokes into an active aperture delivered presentations of the lever-CS, whereas nose pokes into an inactive aperture had no consequences. Across initial autoshaping sessions, goal-tracking behavior, as measured by entries into the fluid port where ethanol was delivered, developed rapidly. However, with extended training goal-tracking diminished, and sign-tracking responses, as measured by lever-CS activations, emerged. Control rats that received explicitly unpaired CS and US presentations did not show goal-tracking or sign-tracking responses. In the test for conditioned reinforcement, rats with CS-US pairings during autoshaping training made more active relative to inactive nose pokes, whereas rats in the unpaired control group did not. Moreover, active nose pokes were positively correlated with sign-tracking behavior during autoshaping. Extended training may produce a shift in the learned properties of Pavlovian alcohol cues, such that after initially predicting alcohol availability they acquire robust incentive salience. PMID:25784867
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Motivational state and reward content determine choice behavior under risk in mice.
Leblond, Mona; Fan, David; Brynildsen, Julia K; Yin, Henry H
2011-01-01
Risk is a ubiquitous feature of the environment for most organisms, who must often choose between a small and certain reward and a larger but less certain reward. To study choice behavior under risk in a genetically well characterized species, we trained mice (C57BL/6) on a discrete trial, concurrent-choice task in which they must choose between two levers. Pressing one lever (safe choice) is always followed by a small reward. Pressing the other lever (risky choice) is followed by a larger reward, but only on some of the trials. The overall payoff is the same on both levers. When mice were not food deprived, they were indifferent to risk, choosing both levers with equal probability regardless of the level of risk. In contrast, following food or water deprivation, mice earning 10% sucrose solution were risk-averse, though the addition of alcohol to the sucrose solution dose-dependently reduced risk aversion, even before the mice became intoxicated. Our results falsify the budget rule in optimal foraging theory often used to explain behavior under risk. Instead, they suggest that the overall demand or desired amount for a particular reward determines risk preference. Changes in motivational state or reward identity affect risk preference by changing demand. Any manipulation that increases the demand for a reward also increases risk aversion, by selectively increasing the frequency of safe choices without affecting frequency of risky choices.
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ERIC Educational Resources Information Center
McDonough, Patricia; Calderone, Shannon
2010-01-01
In the last forty years, federal and state financial aid policy has fundamentally shifted the way in which students and families finance college costs. Whereas grants once served an important function in equalizing college opportunity, loans are now considered a key lever against escalating postsecondary costs (McPherson and Shapiro, 1998). This…
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Sun, Xiaojing; Wang, Yihua; Ajtai, Katalin
2017-01-01
Myosin motors in cardiac ventriculum convert ATP free energy to the work of moving blood volume under pressure. The actin bound motor cyclically rotates its lever-arm/light-chain complex linking motor generated torque to the myosin filament backbone and translating actin against resisting force. Previous research showed that the unloaded in vitro motor is described with high precision by single molecule mechanical characteristics including unitary step-sizes of approximately 3, 5, and 8 nm and their relative step-frequencies of approximately 13, 50, and 37%. The 3 and 8 nm unitary step-sizes are dependent on myosin essential light chain (ELC) N-terminus actin binding. Step-size and step-frequency quantitation specifies in vitro motor function including duty-ratio, power, and strain sensitivity metrics. In vivo, motors integrated into the muscle sarcomere form the more complex and hierarchically functioning muscle machine. The goal of the research reported here is to measure single myosin step-size and step-frequency in vivo to assess how tissue integration impacts motor function. A photoactivatable GFP tags the ventriculum myosin lever-arm/light-chain complex in the beating heart of a live zebrafish embryo. Detected single GFP emission reports time-resolved myosin lever-arm orientation interpreted as step-size and step-frequency providing single myosin mechanical characteristics over the active cycle. Following step-frequency of cardiac ventriculum myosin transitioning from low to high force in relaxed to auxotonic to isometric contraction phases indicates that the imposition of resisting force during contraction causes the motor to down-shift to the 3 nm step-size accounting for >80% of all the steps in the near-isometric phase. At peak force, the ATP initiated actomyosin dissociation is the predominant strain inhibited transition in the native myosin contraction cycle. The proposed model for motor down-shifting and strain sensing involves ELC N-terminus actin binding. Overall, the approach is a unique bottom-up single molecule mechanical characterization of a hierarchically functional native muscle myosin. PMID:28423017
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In Vivo Orientation of Single Myosin Lever Arms in Zebrafish Skeletal Muscle
Sun, Xiaojing; Ekker, Stephen C.; Shelden, Eric A.; Takubo, Naoko; Wang, Yihua; Burghardt, Thomas P.
2014-01-01
Cardiac and skeletal myosin assembled in the muscle lattice power contraction by transducing ATP free energy into the mechanical work of moving actin. Myosin catalytic/lever-arm domains comprise the transduction/mechanical coupling machinery that move actin by lever-arm rotation. In vivo, myosin is crowded and constrained by the fiber lattice as side chains are mutated and otherwise modified under normal, diseased, or aging conditions that collectively define the native myosin environment. Single-myosin detection uniquely defines bottom-up characterization of myosin functionality. The marriage of in vivo and single-myosin detection to study zebrafish embryo models of human muscle disease is a multiscaled technology that allows one-to-one registration of a selected myosin molecular alteration with muscle filament-sarcomere-cell-fiber-tissue-organ- and organism level phenotypes. In vivo single-myosin lever-arm orientation was observed at superresolution using a photoactivatable-green-fluorescent-protein (PAGFP)-tagged myosin light chain expressed in zebrafish skeletal muscle. By simultaneous observation of multiphoton excitation fluorescence emission and second harmonic generation from myosin, we demonstrated tag specificity for the lever arm. Single-molecule detection used highly inclined parallel beam illumination and was verified by quantized photoactivation and photobleaching. Single-molecule emission patterns from relaxed muscle in vivo provided extensive superresolved dipole orientation constraints that were modeled using docking scenarios generated for the myosin (S1) and GFP crystal structures. The dipole orientation data provided sufficient constraints to estimate S1/GFP coordination. The S1/GFP coordination in vivo is rigid and the lever-arm orientation distribution is well-ordered in relaxed muscle. For comparison, single myosins in relaxed permeabilized porcine papillary muscle fibers indicated slightly differently oriented lever arms and rigid S1/GFP coordination. Lever arms in both muscles indicated one preferred spherical polar orientation and widely distributed azimuthal orientations relative to the fiber symmetry axis. Cardiac myosin is more radially displaced from the fiber axis. Probe rigidity implies the PAGFP tag reliably indicates cross-bridge orientation in situ and in vivo. PMID:25229148
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Boomhower, Steven R.; Newland, M. Christopher
2016-01-01
Adolescence is associated with the continued maturation of dopamine neurotransmission and is implicated in the etiology of many psychiatric illnesses. Adolescent exposure to neurotoxicants that distort dopamine neurotransmission, such as methylmercury (MeHg), may modify the effects of chronic d-amphetamine (d-AMP) administration on reversal learning and attentional-set shifting. Male C57Bl/6n mice were randomly assigned to two MeHg-exposure groups (0 ppm and 3 ppm) and two d-AMP-exposure groups (saline and 1 mg/kg/day), producing four treatment groups (n = 10–12/group): Control, MeHg, d-AMP, and MeHg + d-AMP. MeHg exposure (via drinking water) spanned postnatal day 21–59 (the murine adolescent period), and once daily i.p. injections of d-AMP or saline spanned postnatal day 28–42. As adults, mice were trained on a spatial-discrimination-reversal (SDR) task in which the spatial location of a lever press predicted reinforcement. Following two SDRs, a visual-discrimination task (extradimensional shift) was instated in which the presence of a stimulus light above a lever predicted reinforcement. Responding was modeled using a logistic function, which estimated the rate (slope) of a behavioral transition and trials required to complete half a transition (half-max). MeHg, d-AMP, and MeHg + d-AMP exposure increased estimates of half-max on the second reversal. MeHg exposure increased half-max and decreased the slope term following the extradimensional shift, but these effects did not occur following MeHg + d-AMP exposure. MeHg + d-AMP exposure produced more perseverative errors and omissions following a reversal. Adolescent exposure to MeHg can modify the behavioral effects of chronic d-AMP administration. PMID:28287789
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Boomhower, Steven R; Newland, M Christopher
2017-04-01
Adolescence is associated with the continued maturation of dopamine neurotransmission and is implicated in the etiology of many psychiatric illnesses. Adolescent exposure to neurotoxicants that distort dopamine neurotransmission, such as methylmercury (MeHg), may modify the effects of chronic d -amphetamine ( d -AMP) administration on reversal learning and attentional-set shifting. Male C57Bl/6n mice were randomly assigned to two MeHg-exposure groups (0 ppm and 3 ppm) and two d -AMP-exposure groups (saline and 1 mg/kg/day), producing four treatment groups (n = 10-12/group): control, MeHg , d -AMP, and MeHg + d -AMP. MeHg exposure (via drinking water) spanned postnatal days 21-59 (the murine adolescent period), and once daily intraperitoneal injections of d -AMP or saline spanned postnatal days 28-42. As adults, mice were trained on a spatial-discrimination-reversal (SDR) task in which the spatial location of a lever press predicted reinforcement. Following 2 SDRs, a visual-discrimination task (extradimensional shift) was instated in which the presence of a stimulus light above a lever predicted reinforcement. Responding was modeled using a logistic function, which estimated the rate (slope) of a behavioral transition and trials required to complete half a transition (half-max). MeHg, d -AMP, and MeHg + d -AMP exposure increased estimates of half-max on the second reversal. MeHg exposure increased half-max and decreased the slope term following the extradimensional shift, but these effects did not occur following MeHg + d -AMP exposure. MeHg + d -AMP exposure produced more perseverative errors and omissions following a reversal. Adolescent exposure to MeHg can modify the behavioral effects of chronic d -AMP administration. (PsycINFO Database Record (c) 2017 APA, all rights reserved).
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Sexual dimorphism and feeding ecology of Diamond-backed Terrapins (Malaclemys terrapin)
Underwood, Elizabeth B.; Bowers, Sarah; Guzy, Jacquelyn C.; Lovich, Jeffrey E.; Taylor, Carole A.; Gibbons, J. Whitfield; Dorcas, Michael E.
2013-01-01
Natural and sexual selection are frequently invoked as causes of sexual size dimorphism in animals. Many species of turtles, including the Diamond-backed Terrapin (Malaclemys terrapin), exhibit sexual dimorphism in body size, possibly enabling the sexes to exploit different resources and reduce intraspecific competition. Female terrapins not only have larger body sizes but also disproportionately larger skulls and jaws relative to males. To better understand the relationship between skull morphology and terrapin feeding ecology, we measured the in-lever to out-lever ratios of 27 male and 33 female terrapin jaws to evaluate biomechanics of the trophic apparatus. In addition, we measured prey handling times by feeding Fiddler Crabs (Uca pugnax), a natural prey item, to 24 terrapins in the laboratory. Our results indicate that although females have disproportionately larger heads, they have similar in:out lever ratios to males, suggesting that differences in adductor muscle mass are more important in determining bite force than jaw in:out lever ratios. Females also had considerably reduced prey handling times. Understanding the factors affecting terrapin feeding ecology can illuminate the potential roles male and female terrapins play as top-down predators that regulate grazing of Periwinkle Snails (Littorina irrorata) on Cord Grass (Spartina alterniflora).
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3. ONE OF SIX SPUR GEARS AND CABLE SPOOLS INSTALLED ...
3. ONE OF SIX SPUR GEARS AND CABLE SPOOLS INSTALLED IN THE UPPER FALLS GATE HOUSE. THE SHIFTING LEVER IS VISIBLE IN FOREGROUND, AS IS THE 3X3 1/16 SHAFT, LOOKING EAST, NORTHEAST. - Washington Water Power Spokane River Upper Falls Hydroelectric Development, Gates & Gate-Lifting Mechanisms, Spokane River, approximately 0.5 mile northeast of intersection of Spokane Falls Boulevard & Post Street, Spokane, Spokane County, WA
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Motivational State and Reward Content Determine Choice Behavior under Risk in Mice
Leblond, Mona; Fan, David; Brynildsen, Julia K.; Yin, Henry H.
2011-01-01
Risk is a ubiquitous feature of the environment for most organisms, who must often choose between a small and certain reward and a larger but less certain reward. To study choice behavior under risk in a genetically well characterized species, we trained mice (C57BL/6) on a discrete trial, concurrent-choice task in which they must choose between two levers. Pressing one lever (safe choice) is always followed by a small reward. Pressing the other lever (risky choice) is followed by a larger reward, but only on some of the trials. The overall payoff is the same on both levers. When mice were not food deprived, they were indifferent to risk, choosing both levers with equal probability regardless of the level of risk. In contrast, following food or water deprivation, mice earning 10% sucrose solution were risk-averse, though the addition of alcohol to the sucrose solution dose-dependently reduced risk aversion, even before the mice became intoxicated. Our results falsify the budget rule in optimal foraging theory often used to explain behavior under risk. Instead, they suggest that the overall demand or desired amount for a particular reward determines risk preference. Changes in motivational state or reward identity affect risk preference by changing demand. Any manipulation that increases the demand for a reward also increases risk aversion, by selectively increasing the frequency of safe choices without affecting frequency of risky choices. PMID:21966504
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DiFeliceantonio, Alexandra G.; Berridge, Kent C.
2016-01-01
Pavlovian cues for rewards can become attractive incentives: approached and ‘wanted’ as the rewards themselves. The motivational attractiveness of a previously learned cue is not fixed, but can be dynamically amplified during re-encounter by simultaneous activation of brain limbic circuitry. Here we report that opioid or dopamine microinjections in the dorsolateral quadrant of the neostriatum (DLS) of rats selectively amplify attraction toward a previously learned Pavlovian cue in an individualized fashion, at the expense of a competing cue. In an autoshaping (sign-tracking vs goal-tracking) paradigm, microinjection of the mu opioid receptor agonist (DAMGO) or dopamine indirect agonist (amphetamine) in DLS of sign-tracker individuals selectively enhanced their sign-tracking attraction toward the reward-predictive lever cue. By contrast, DAMGO or amphetamine in DLS of goal-trackers selectively enhanced prepotent attraction toward the reward-proximal cue of sucrose dish. Amphetamine also enhanced goal-tracking in some sign-tracker individuals (if they ever defected to the dish even once). That DLS enhancement of cue attraction was due to stronger motivation, not stronger habits was suggested by: 1) sign-trackers flexibly followed their cue to a new location when the lever was suddenly moved after DLS DAMGO microinjection, and 2) DAMGO in DLS also made sign-trackers work harder on a new instrumental nose-poke response required to earn presentations of their Pavlovian lever cue (instrumental conditioned reinforcement). Altogether, our results suggest that DLS circuitry can enhance the incentive salience of a Pavlovian reward cue, selectively making that cue a stronger motivational magnet. PMID:26924040
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Drug versus sweet reward: greater attraction to and preference for sweet versus drug cues.
Madsen, Heather B; Ahmed, Serge H
2015-05-01
Despite the unique ability of addictive drugs to directly activate brain reward circuits, recent evidence suggests that drugs induce reinforcing and incentive effects that are comparable to, or even lower than some nondrug rewards. In particular, when rats have a choice between pressing a lever associated with intravenous cocaine or heroin delivery and another lever associated with sweet water delivery, most respond on the latter. This outcome suggests that sweet water is more reinforcing and attractive than either drug. However, this outcome may also be due to the differential ability of sweet versus drug levers to elicit Pavlovian feeding-like conditioned responses that can cause involuntary lever pressing, such as pawing and biting the lever. To test this hypothesis, rats first underwent Pavlovian conditioning to associate one lever with sweet water (0.2% saccharin) and a different lever with intravenous cocaine (0.25 mg) or heroin (0.01 mg). Choice between these two levers was then assessed under two operant choice procedures: one that permitted the expression of Pavlovian-conditioned lever press responses during choice, the other not. During conditioning, Pavlovian-conditioned lever press responses were considerably higher on the sweet lever than on either drug lever, and slightly greater on the heroin lever than on the cocaine lever. Importantly, though these differences in Pavlovian-conditioned behavior predicted subsequent preference for sweet water during choice, they were not required for its expression. Overall, this study confirms that rats prefer the sweet lever because sweet water is more reinforcing and attractive than cocaine or heroin. © 2014 Society for the Study of Addiction.
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Reilly, Stephen M; McElroy, Eric J; White, Thomas D; Biknevicius, Audrone R; Bennett, Michael B
2010-04-01
Mammals have four hypaxial muscle layers that wrap around the abdomen between the pelvis, ribcage, and spine. However, the marsupials have epipubic bones extending anteriorly into the ventral hypaxial layers with two additional muscles extending to the ventral midline and femur. Comparisons of South American marsupials to basal eutherians have shown that all of the abdominal hypaxials are active bilaterally in resting ventilation. However, during locomotion marsupials employ an asymmetrical pattern of activity as the hypaxial muscles form a crosscouplet linkage that uses the epipubic bone as a lever to provide long-axis support of the body between diagonal limb couplets during each step. In basal eutherians, this system shifts off the femur and epipubic bones (which are lost) resulting in a shoulder to pelvis linkage associated with shifts in both the positions and activity patterns of the pectineus and rectus abdominis muscles during locomotion. In this study, we present data on hypaxial function in two species (Pseudocheirus peregrinus and Trichosurus vulpecula) representing the two major radiations of possums in Australia: the Pseudocheiridae (within the Petauroidea) and the Phalangeridae. Patterns of gait, motor activity, and morphology in these two Australian species were compared with previous work to examine the generality of 1) the crosscouplet lever system as the basal condition for the Marsupialia and 2) several traits hypothesized to be common to all mammals (hypaxial tonus during resting ventilation, ventilation to step synchrony during locomotion, and bilateral transversus abdominis activity during locomotor expiration). Our results validate the presence of the crosscouplet pattern and basic epipubic bone lever system in Australian possums and confirm the generality of basal mammalian patterns. However, several novelties discovered in Trichosurus, reveal that it exhibits an evolutionary transition to intermediate eutherian-like morphological and motor patterns paralleling many other unique features of this species. (c) 2009 Wiley-Liss, Inc.
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Eagle, Dawn M.; Noschang, Cristie; d’Angelo, Laure-Sophie Camilla; Noble, Christie A.; Day, Jacob O.; Dongelmans, Marie Louise; Theobald, David E.; Mar, Adam C.; Urcelay, Gonzalo P.; Morein-Zamir, Sharon; Robbins, Trevor W.
2014-01-01
Excessive checking is a common, debilitating symptom of obsessive-compulsive disorder (OCD). In an established rodent model of OCD checking behaviour, quinpirole (dopamine D2/3-receptor agonist) increased checking in open-field tests, indicating dopaminergic modulation of checking-like behaviours. We designed a novel operant paradigm for rats (observing response task (ORT)) to further examine cognitive processes underpinning checking behaviour and clarify how and why checking develops. We investigated i) how quinpirole increases checking, ii) dependence of these effects on D2/3 receptor function (following treatment with D2/3 receptor antagonist sulpiride) and iii) effects of reward uncertainty. In the ORT, rats pressed an ‘observing’ lever for information about the location of an ‘active’ lever that provided food reinforcement. High- and low-checkers (defined from baseline observing) received quinpirole (0.5 mg/kg, 10 treatments) or vehicle. Parametric task manipulations assessed observing/checking under increasing task demands relating to reinforcement uncertainty (variable response requirement and active-lever location switching). Treatment with sulpiride further probed the pharmacological basis of long-term behavioural changes. Quinpirole selectively increased checking, both functional observing lever presses (OLPs) and non-functional extra OLPs (EOLPs). The increase in OLPs and EOLPs was long-lasting, without further quinpirole administration. Quinpirole did not affect the immediate ability to use information from checking. Vehicle and quinpirole-treated rats (VEH and QNP respectively) were selectively sensitive to different forms of uncertainty. Sulpiride reduced non-functional EOLPs in QNP rats but had no effect on functional OLPs. These data have implications for treatment of compulsive checking in OCD, particularly for serotonin-reuptake-inhibitor treatment-refractory cases, where supplementation with dopamine receptor antagonists may be beneficial. PMID:24406720
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Swalve, Natashia; Barrett, Scott T.; Bevins, Rick A.; Li, Ming
2015-01-01
Nicotine is a widely-abused drug, yet its primary reinforcing effect does not seem potent as other stimulants such as cocaine. Recent research on the contributing factors toward chronic use of nicotine-containing products has implicated the role of reinforcement-enhancing effects of nicotine. The present study investigates whether phencyclidine (PCP) may also possess a reinforcement-enhancement effect and how this may interact with the reinforcement-enhancement effect of nicotine. PCP was tested for two reasons: 1) it produces discrepant results on overall reward, similar to that seen with nicotine and 2) it may elucidate how other compounds may interact with the reinforcement-enhancement of nicotine. Adult male Sprague-Dawley rats were trained to lever press for brief visual stimulus presentations under fixed-ratio (FR) schedules of reinforcement and then were tested with nicotine (0.2 or 0.4 mg/kg) and/or PCP (2.0 mg/kg) over six increasing FR values. A selective increase in active lever-pressing for the visual stimulus with drug treatment was considered evidence of a reinforcement-enhancement effect. PCP and nicotine separately increased active lever pressing for a visual stimulus in a dose-dependent manner and across the different FR schedules. The addition of PCP to nicotine did not increase lever-pressing for the visual stimulus, possibly due to a ceiling effect. The effect of PCP may be driven largely by its locomotor stimulant effects, whereas the effect of nicotine was independent of locomotor stimulation. This dissociation emphasizes that distinct pharmacological properties contribute to the reinforcement-enhancement effects of substances. PMID:26026783
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Adrenalectomy eliminates the extinction spike in autoshaping with rats.
Thomas, B L; Papini, M R
2001-03-01
Experiment 1, using rats, investigated the effect of adrenalectomy (ADX) on the invigoration of lever-contact performance that occurs in the autoshaping situation after a shift from acquisition to extinction (called the extinction spike). Groups of rats with ADX or sham operations were trained under spaced and massed conditions [average intertrial intervals (ITI) of either 15 or 90 s] for 10 sessions and then shifted to extinction. ADX did not affect acquisition training but it eliminated the extinction spike. Plasma corticosterone levels during acquisition were shown in Experiment 2 to be similar in rats trained under spaced or massed conditions. Adrenal participation in the emotional arousal induced by conditions of surprising nonreward (e.g., extinction) is discussed.
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DiFeliceantonio, Alexandra G; Berridge, Kent C
2016-05-01
Pavlovian cues for rewards can become attractive incentives: approached and 'wanted' as the rewards themselves. The motivational attractiveness of a previously learned cue is not fixed, but can be dynamically amplified during re-encounter by simultaneous activation of brain limbic circuitry. Here it was reported that opioid or dopamine microinjections in the dorsolateral quadrant of the neostriatum (DLS) of rats selectively amplify attraction toward a previously learned Pavlovian cue in an individualized fashion, at the expense of a competing cue. In an autoshaping (sign-tracking vs. goal-tracking) paradigm, microinjection of the mu opioid receptor agonist (DAMGO) or dopamine indirect agonist (amphetamine) in the DLS of sign-tracker individuals selectively enhanced their sign-tracking attraction toward the reward-predictive lever cue. By contrast, DAMGO or amphetamine in the DLS of goal-trackers selectively enhanced prepotent attraction toward the reward-proximal cue of sucrose dish. Amphetamine also enhanced goal-tracking in some sign-tracker individuals (if they ever defected to the dish even once). That DLS enhancement of cue attraction was due to stronger motivation, not stronger habits, was suggested by: (i) sign-trackers flexibly followed their cue to a new location when the lever was suddenly moved after DLS DAMGO microinjection; and (ii) DAMGO in the DLS also made sign-trackers work harder on a new instrumental nose-poke response required to earn presentations of their Pavlovian lever cue (instrumental conditioned reinforcement). Altogether, the current results suggest that DLS circuitry can enhance the incentive salience of a Pavlovian reward cue, selectively making that cue a stronger motivational magnet. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.
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Punishment and the potential for negative reinforcement with histamine injection.
Mayer, Paulo César Morales; de Carvalho Neto, Marcus Bentes; Katz, Jonathan L
2018-03-01
The present study examined punishment of responding with histamine injection, and its potential to generate avoidance of punishment. Sprague-Dawley rats were trained under concurrent schedules in which responses on one lever (the punishment lever) produced food under a variable-interval schedule, and under some conditions intermittent injections of histamine, which suppressed behavior. Responses on a second (avoidance) lever prevented histamine injections scheduled on the punishment lever. After stabilization of punished responding, a variable-interval 15-s schedule of cancellation of histamine (avoidance) was added for responding on the second/avoidance lever, without subsequent acquisition of responding on that lever. Progressive decreases in the length of the punishment variable-interval schedule increased suppression on the punishment lever without increases in response rates on the avoidance lever. Exchanging contingencies on the levers ensured that response rates on the avoidance lever were sufficiently high to decrease the histamine injection frequency; nonetheless response rates on the avoidance lever decreased over subsequent sessions. Under no condition was responding maintained on the avoidance lever despite continued punishing effectiveness of histamine throughout. The present results suggest that avoidance conditioning is not a necessary condition for effective punishment, and confirm the importance of empirical rather than presumed categorization of behavioral effects of stimulus events. Published 2018. This article is a U.S. Government work and is in the public domain in the USA.
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Remote control of molecular motors using light-activated gearshifting
NASA Astrophysics Data System (ADS)
Bryant, Zev
2013-03-01
Engineering molecular motors with dynamically controllable properties will allow selective perturbation of mechanical processes in vivo and provide sophisticated components for directed nanoscale transport in vitro. We previously constructed myosin motors that respond to a change in [Ca++] by reversing their direction of motion along the polarized actin filament. To expand the potential applications of controllable molecular motors, we have now developed myosins that shift gears in response to blue light illumination. Light is a versatile control signal that can be readily modulated in time and space, and is generally orthogonal to cellular signaling. Using structure-guided protein engineering, we have incorporated LOV photoreceptor domains into the lever arms of chimeric myosins, resulting in motors that robustly speed up, slow down, or switch directions upon illumination. These genetically encoded motors should be directly deployable inside living cells. Our successful designs include constructs based on two different myosin classes, and we show that optical velocity control can be implemented in motors that move at microns/sec speeds, enabling practical biological and bioengineering applications.
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Stereotypes for lever-tap operation.
Chan, Alan H S; Tsang, Steve N H; Hoffmann, Errol R
2016-04-15
Lever-operated taps have become more popular and are commonly used in operating theatres, food preparation areas and where users have poor strength; however, there is very little data available for user expectations on tap operation. Thus, an experiment on dual lever-operated water tap (faucets) was conducted with the aim of for providing information for improved design. This study aims to compare different lever-tap designs and their stereotypes adopted by the end-user to operate them also to verify the stereotypes for increasing or decreasing the water flow. 240 participants were requested to rotate the lever tap to indicate direction for increasing and decreasing water flow with simulated hardware, using actual taps placed at the top of a simulated washbasin. Nine initial positions of the lever were used for increasing and decreasing flows, ranging from the ends of both levers facing outward from the bowl center to the ends of both levers facing inward. All levers operated in the horizontal plane. Strong stereotypes (greater than 80%) for several initial lever orientations were found for increasing water flow, especially when the initial lever end positions were facing outwards. However, for different initial positions at which participants were told that the water was flowing and the flow was to be decreased, no strong stereotypes existed. The stereotypes for increasing water flow of dual-lever taps were strong, whereas those for decreasing water flow were weak and hence the stereotype reversibility was also weak. In terms of user expectations, lever taps do not show any great advantage over cross-taps in terms of operator expectations for increasing and decreasing water flow.
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McKerchar, Todd L; Zarcone, Troy J; Fowler, Stephen C
2005-01-01
Recent progress in mouse genetics has led to an increased interest in developing procedures for assessing mouse behavior, but relatively few of the behavioral procedures developed involve positively reinforced operant behavior. When operant methods are used, nose poking, not lever pressing, is the target response. In the current study differential acquisition of milk-reinforced lever pressing was observed in five inbred strains (C57BL/6J, DBA/2J, 129X1/SvJ, C3H/HeJ, and BALB/cJ) and one outbred stock (CD-1) of mice. Regardless of whether one or two levers (an “operative” and “inoperative” lever) were in the operant chamber, a concomitant variable-time fixed-ratio schedule of milk reinforcement established lever pressing in the majority of mice within two 120-min sessions. Substantial differences in lever pressing were observed across mice and between procedures. Adding an inoperative lever retarded acquisition in C57BL/6J, DBA/2J, 129X1/SvJ, and C3H/HeJ mice, but not in CD-1 and BALB/cJ mice. Locomotor activity was positively correlated with number of lever presses in both procedures. Analyses of durations of the subcomponents (e.g., time to move from hopper to lever) of operant behavior revealed further differences among the six types of mice. Together, the data suggest that appetitively reinforced lever pressing can be acquired rapidly in mice and that a combination of procedural, behavioral, and genetic variables contributes to this acquisition. PMID:16596969
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Smith, Ian M; Pang, Kevin C H; Servatius, Richard J; Jiao, Xilu; Beck, Kevin D
2016-10-01
The perseveration of avoidance behavior, even in the absence of once threatening stimuli, is a key feature of anxiety and related psychiatric conditions. This phenomenon can be observed in the Wistar-Kyoto (WKY) rat which, in comparison to outbred controls, demonstrates impaired extinction of avoidance behavior. Also characteristic of the WKY rat is abnormalities of the neurocircuitry and neuroplasticity of the medial prefrontal cortex (mPFC). One means of reducing physiological responses to anxiety, and conditioned fear, in social species is the presence of a conspecific animal. The current study investigates whether or not pair-housed WKY rats would show facilitated extinction of avoidance in comparison to individual-housed WKY rats, and whether or not pair-housing influences mPFC activation during lever-press avoidance. Male WKY rats were assigned to individual-housed and pair-housed conditions. Rats were trained in lever-press avoidance. Each session of lever-press avoidance consisted of 20 trials, where pressing a lever in response to a warning tone prevented foot-shocks. Rats received 12 acquisition sessions over 4weeks; followed by 6 extinction sessions over 2weeks, where foot-shocks ceased to be delivered. Brains were harvested 90min after trials 1 and 10 of extinction sessions 1 and 6, and mPFC sections underwent c-Fos staining as a measure of activation. Pair-housed rats showed facilitated lever-press avoidance extinction rates, but the main cause for this overall difference was a selective facilitation of within-session extinction. Similar to individual-housed rats, pair-housed rats continued to avoid during trial 1 of extinction even when the avoidance responding had been significantly reduced by the end of the previous session. Pair-housed rats sacrificed on trial 1 showed greater c-Fos expression in the anterior cingulate cortex and prelimbic cortex subregions of the mPFC compared individual-housed rats sacrificed on trial 1. This data shows pair-housing to facilitate the extinction of avoidance, and to influence activity of the mPFC, in WKY rats. Despite this environmental manipulation, the pair-housed WKY rats continued to show avoidance responding on trial 1 of extinction sessions. This demonstrates that within-session extinction can be dissociated from between-session extinction-resistance in WKY rats. Furthermore, it suggests the individual-housing of WKY rats selectively slows within-session extinction, possibly by reducing neuronal activity of the mPFC during the testing situation. Published by Elsevier Inc.
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Levesque, Jean-Frederic; Sutherland, Kim
2017-01-01
Objective Across healthcare systems, there is consensus on the need for independent and impartial assessment of performance. There is less agreement about how measurement and reporting performance improves healthcare. This paper draws on academic theories to develop a conceptual framework—one that classifies in an integrated manner the ways in which change can be leveraged by healthcare performance information. Methods A synthesis of published frameworks. Results The framework identifies eight levers for change enabled by performance information, spanning internal and external drivers, and emergent and planned processes: (1) cognitive levers provide awareness and understanding; (2) mimetic levers inform about the performance of others to encourage emulation; (3) supportive levers provide facilitation, implementation tools or models of care to actively support change; (4) formative levers develop capabilities and skills through teaching, mentoring and feedback; (5) normative levers set performance against guidelines, standards, certification and accreditation processes; (6) coercive levers use policies, regulations incentives and disincentives to force change; (7) structural levers modify the physical environment or professional cultures and routines; (8) competitive levers attract patients or funders. Conclusion This framework highlights how performance measurement and reporting can contribute to eight different levers for change. It provides guidance into how to align performance measurement and reporting into quality improvement programme. PMID:28851769
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Swalve, Natashia; Barrett, Scott T; Bevins, Rick A; Li, Ming
2015-09-15
Nicotine is a widely-abused drug, yet its primary reinforcing effect does not seem potent as other stimulants such as cocaine. Recent research on the contributing factors toward chronic use of nicotine-containing products has implicated the role of reinforcement-enhancing effects of nicotine. The present study investigates whether phencyclidine (PCP) may also possess a reinforcement-enhancement effect and how this may interact with the reinforcement-enhancement effect of nicotine. PCP was tested for two reasons: (1) it produces discrepant results on overall reward, similar to that seen with nicotine and (2) it may elucidate how other compounds may interact with the reinforcement-enhancement of nicotine. Adult male Sprague-Dawley rats were trained to lever press for brief visual stimulus presentations under fixed-ratio (FR) schedules of reinforcement and then were tested with nicotine (0.2 or 0.4 mg/kg) and/or PCP (2.0mg/kg) over six increasing FR values. A selective increase in active lever-pressing for the visual stimulus with drug treatment was considered evidence of a reinforcement-enhancement effect. PCP and nicotine separately increased active lever pressing for a visual stimulus in a dose-dependent manner and across the different FR schedules. The addition of PCP to nicotine did not increase lever-pressing for the visual stimulus, possibly due to a ceiling effect. The effect of PCP may be driven largely by its locomotor stimulant effects, whereas the effect of nicotine was independent of locomotor stimulation. This dissociation emphasizes that distinct pharmacological properties contribute to the reinforcement-enhancement effects of substances. Copyright © 2015 Elsevier B.V. All rights reserved.
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Randall, Patrick A; Pardo, Marta; Nunes, Eric J; López Cruz, Laura; Vemuri, V Kiran; Makriyannis, Alex; Baqi, Younis; Müller, Christa E; Correa, Mercè; Salamone, John D
2012-01-01
Mesolimbic dopamine (DA) is involved in behavioral activation and effort-related processes. Rats with impaired DA transmission reallocate their instrumental behavior away from food-reinforced tasks with high response requirements, and instead select less effortful food-seeking behaviors. In the present study, the effects of several drug treatments were assessed using a progressive ratio (PROG)/chow feeding concurrent choice task. With this task, rats can lever press on a PROG schedule reinforced by a preferred high-carbohydrate food pellet, or alternatively approach and consume the less-preferred but concurrently available laboratory chow. Rats pass through each ratio level 15 times, after which the ratio requirement is incremented by one additional response. The DA D(2) antagonist haloperidol (0.025-0.1 mg/kg) reduced number of lever presses and highest ratio achieved but did not reduce chow intake. In contrast, the adenosine A(2A) antagonist MSX-3 increased lever presses and highest ratio achieved, but decreased chow consumption. The cannabinoid CB1 inverse agonist and putative appetite suppressant AM251 decreased lever presses, highest ratio achieved, and chow intake; this effect was similar to that produced by pre-feeding. Furthermore, DA-related signal transduction activity (pDARPP-32(Thr34) expression) was greater in nucleus accumbens core of high responders (rats with high lever pressing output) compared to low responders. Thus, the effects of DA antagonism differed greatly from those produced by pre-feeding or reduced CB1 transmission, and it appears unlikely that haloperidol reduces PROG responding because of a general reduction in primary food motivation or the unconditioned reinforcing properties of food. Furthermore, accumbens core signal transduction activity is related to individual differences in work output.
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Pharmacological specificity of N-methyl-D-aspartate discrimination in rats.
Grech, D M; Willetts, J; Balster, R L
1993-04-01
The purpose of this study was to provide further information on the usefulness of N-methyl-D-aspartate (NMDA) discrimination in rats as a behavioral model for NMDA receptor activation. The pharmacological specificity of the NMDA discriminative stimulus was examined in rats trained to discriminate 30 mg/kg, i.p. NMDA from saline using a 2-lever fixed-ratio (FR) 32 food reinforcement schedule. Pharmacologically diverse centrally-acting agents were examined for their ability to substitute for NMDA. Morphine did not substitute for NMDA; neither did the central stimulants, caffeine and (+)-amphetamine, which produced a maximum mean of only 16 and 35% NMDA-lever responding, respectively. Pentylenetetrazol and picrotoxin also did not substitute for NMDA. Compounds interacting with cholinergic neurotransmission including nicotine, physostigmine, arecoline and mecamylamine, produced at best, only intermediate levels of NMDA-lever responding (32-61%), with the highest levels of NMDA-lever responding generally occurring at doses that also reduced rates of responding. These results suggest that the discriminative stimulus properties of NMDA are dissimilar from those of a number of centrally-acting drugs. Combined with the results of studies indicating that the NMDA discriminative stimulus can be antagonized by competitive NMDA antagonists, these results provide further evidence that NMDA receptor activation is the basis of NMDA discrimination and that this model may be useful for studying site-selective NMDA agonists and antagonists.
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Gremel, Christina M.; Costa, Rui M.
2014-01-01
Shifting between goal-directed and habitual actions allows for efficient and flexible decision-making. Here we demonstrate a novel, within-subject instrumental lever-pressing paradigm where mice shift between goal-directed and habitual actions. We identify a role for orbitofrontal cortex (OFC) in actions following outcome-revaluation, and confirm that dorsal medial (DMS) and lateral striatum (DLS) mediate different action strategies. In-vivo simultaneous recordings of OFC, DMS, and DLS neuronal ensembles during shifting reveal that the same neurons display different activity depending on whether presses are goal-directed or habitual, with DMS and OFC becoming more—and DLS less-engaged during goal-directed actions. Importantly, the magnitude of neural activity changes in OFC following changes in outcome value positively correlates with the level of goal-directed behavior. Chemogenetic inhibition of OFC disruptsgoal-directed actions, while optogenetic activation of OFC specifically increases goal-directed pressing. They also reveal a role for OFC in action revaluation, which has implications for understanding compulsive behavior. PMID:23921250
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14. INTERIOR OF MAIN DECKNOTE LEVERS FROM CEILING CONTROLLED BY ...
14. INTERIOR OF MAIN DECK--NOTE LEVERS FROM CEILING CONTROLLED BY OPERATOR. LEFT HAND LEVER CONTROLLED THROTTLE, RIGHT HAND LEVER CONTROLLED SHOT GUN SWINGER. - Dredge CINCINNATI, Docked on Ohio River at foot of Lighthill Street, Pittsburgh, Allegheny County, PA
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Levesque, Jean-Frederic; Sutherland, Kim
2017-08-28
Across healthcare systems, there is consensus on the need for independent and impartial assessment of performance. There is less agreement about how measurement and reporting performance improves healthcare. This paper draws on academic theories to develop a conceptual framework-one that classifies in an integrated manner the ways in which change can be leveraged by healthcare performance information. A synthesis of published frameworks. The framework identifies eight levers for change enabled by performance information, spanning internal and external drivers, and emergent and planned processes: (1) cognitive levers provide awareness and understanding; (2) mimetic levers inform about the performance of others to encourage emulation; (3) supportive levers provide facilitation, implementation tools or models of care to actively support change; (4) formative levers develop capabilities and skills through teaching, mentoring and feedback; (5) normative levers set performance against guidelines, standards, certification and accreditation processes; (6) coercive levers use policies, regulations incentives and disincentives to force change; (7) structural levers modify the physical environment or professional cultures and routines; (8) competitive levers attract patients or funders. This framework highlights how performance measurement and reporting can contribute to eight different levers for change. It provides guidance into how to align performance measurement and reporting into quality improvement programme. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
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Code of Federal Regulations, 2010 CFR
2010-10-01
... between electrical and mechanical levers. 236.340 Section 236.340 Transportation Other Regulations... Electromechanical interlocking machine; locking between electrical and mechanical levers. In electro-mechanical interlocking machine, locking between electric and mechanical levers shall be maintained so that mechanical...
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Response-food delay gradients for lever pressing and schedule-induced licking in rats.
Pellón, Ricardo; Pérez-Padilla, Angeles
2013-06-01
Eight food-deprived Wistar rats developed stable patterns of lever pressing and licking when exposed to a fixed-time 30-s schedule of food pellet presentation. The rats were trained to lever press by presenting the lever 10 s before the programmed food delivery, with the food pellet being delivered immediately upon a lever press. The operant contingency was then removed and the lever was inserted through the entire interfood interval, being withdrawn with food delivery and reinserted 2 s later. On successive phases of the study, a protective contingency postponed food delivery if responses (lever presses or licks) occurred within the last 1, 2, 5, 10, 20, or 25 s of the interfood interval. Lever pressing was reduced at much shorter response-food delays than those that reduced licking. These results demonstrate that reinforcement contributes to the maintenance of different response patterns on periodic schedules, and that different responses are differentially sensitive to delays.
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Eagle, Dawn M; Noschang, Cristie; d'Angelo, Laure-Sophie Camilla; Noble, Christie A; Day, Jacob O; Dongelmans, Marie Louise; Theobald, David E; Mar, Adam C; Urcelay, Gonzalo P; Morein-Zamir, Sharon; Robbins, Trevor W
2014-05-01
Excessive checking is a common, debilitating symptom of obsessive-compulsive disorder (OCD). In an established rodent model of OCD checking behaviour, quinpirole (dopamine D2/3-receptor agonist) increased checking in open-field tests, indicating dopaminergic modulation of checking-like behaviours. We designed a novel operant paradigm for rats (observing response task (ORT)) to further examine cognitive processes underpinning checking behaviour and clarify how and why checking develops. We investigated i) how quinpirole increases checking, ii) dependence of these effects on D2/3 receptor function (following treatment with D2/3 receptor antagonist sulpiride) and iii) effects of reward uncertainty. In the ORT, rats pressed an 'observing' lever for information about the location of an 'active' lever that provided food reinforcement. High- and low-checkers (defined from baseline observing) received quinpirole (0.5mg/kg, 10 treatments) or vehicle. Parametric task manipulations assessed observing/checking under increasing task demands relating to reinforcement uncertainty (variable response requirement and active-lever location switching). Treatment with sulpiride further probed the pharmacological basis of long-term behavioural changes. Quinpirole selectively increased checking, both functional observing lever presses (OLPs) and non-functional extra OLPs (EOLPs). The increase in OLPs and EOLPs was long-lasting, without further quinpirole administration. Quinpirole did not affect the immediate ability to use information from checking. Vehicle and quinpirole-treated rats (VEH and QNP respectively) were selectively sensitive to different forms of uncertainty. Sulpiride reduced non-functional EOLPs in QNP rats but had no effect on functional OLPs. These data have implications for treatment of compulsive checking in OCD, particularly for serotonin-reuptake-inhibitor treatment-refractory cases, where supplementation with dopamine receptor antagonists may be beneficial. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.
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Acute ethanol effects on neural encoding of reward size and delay in the nucleus accumbens
Gutman, Andrea L.
2016-01-01
Acute ethanol administration can cause impulsivity, resulting in increased preference for immediately available rewards over delayed but more valuable alternatives. The manner in which reward size and delay are represented in neural firing is not fully understood, and very little is known about ethanol effects on this encoding. To address this issue, we used in vivo electrophysiology to characterize neural firing in the core of the nucleus accumbens (NAcc) in rats responding for rewards that varied in size or delay after vehicle or ethanol administration. The NAcc is a central element in the circuit that governs decision-making and importantly, promotes choice of delayed rewards. We found that NAcc firing in response to reward-predictive cues encoded anticipated reward value after vehicle administration, but ethanol administration disrupted this encoding, resulting in a loss of discrimination between immediate and delayed rewards in cue-evoked neural responses. In addition, NAcc firing occurring at the time of the operant response (lever pressing) was inversely correlated with behavioral response latency, such that increased firing rates were associated with decreased latencies to lever press. Ethanol administration selectively attenuated this lever press-evoked firing when delayed but not immediate rewards were expected. These effects on neural firing were accompanied by increased behavioral latencies to respond for delayed rewards. Our results suggest that ethanol effects on NAcc cue- and lever press-evoked encoding may contribute to ethanol-induced impulsivity. PMID:27169507
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Using clinical governance levers to support change in a cancer care reform.
Brault, Isabelle; Denis, Jean-Louis; Sullivan, Terrence James
2015-01-01
Introducing change is a difficult issue facing all health care systems. The use of various clinical governance levers can facilitate change in health care systems. The purpose of this paper is to define clinical governance levers, and to illustrate their use in a large-scale transformation. The empirical analysis deals with the in-depth study of a specific case, which is the organizational model for Ontario's cancer sector. The authors used a qualitative research strategy and drew the data from three sources: semi-structured interviews, analysis of documents, and non-participative observations. From the results, the authors identified three phases and several steps in the reform of cancer services in this province. The authors conclude that a combination of clinical governance levers was used to transform the system. These levers operated at different levels of the system to meet the targeted objectives. To exercise clinical governance, managers need to acquire new competencies. Mobilizing clinical governance levers requires in-depth understanding of the role and scope of clinical governance levers. This study provides a better understanding of clinical governance levers. Clinical governance levers are used to implement an organizational environment that is conducive to developing clinical practice, as well as to act directly on practices to improve quality of care.
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An analysis of policy levers used to implement mental health reform in Australia 1992-2012.
Grace, Francesca C; Meurk, Carla S; Head, Brian W; Hall, Wayne D; Carstensen, Georgia; Harris, Meredith G; Whiteford, Harvey A
2015-10-24
Over the past two decades, mental health reform in Australia has received unprecedented government attention. This study explored how five policy levers (organisation, regulation, community education, finance and payment) were used by the Australian Federal Government to implement mental health reforms. Australian Government publications, including the four mental health plans (published in 1992, 1998, 2003 and 2008) were analysed according to policy levers used to drive reform across five priority areas: [1] human rights and community attitudes; [2] responding to community need; [3] service structures; [4] service quality and effectiveness; and [5] resources and service access. Policy levers were applied in varying ways; with two or three levers often concurrently used to implement a single initiative or strategy. For example, changes to service structures were achieved using various combinations of all five levers. Attempts to improve service quality and effectiveness were instead made through a single lever-regulation. The use of some levers changed over time, including a move away from prescriptive, legislative use of regulation, towards a greater focus on monitoring service standards and consumer outcomes. Patterns in the application of policy levers across the National Mental Health Strategy, as identified in this analysis, represent a novel way of conceptualising the history of mental health reform in Australia. An improved understanding of the strategic targeting and appropriate utilisation of policy levers may assist in the delivery and evaluation of evidence-based mental health reform in the future.
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Lightweight Seat Lever Operation Characteristics
NASA Technical Reports Server (NTRS)
Rajulu, Sudhakar
1999-01-01
In 1999, a Shuttle crew member was unable to operate the backrest lever for the lightweight seat in microgravity. It is essential that crew members can adjust this backrest lever, which is titled forward during launch and then moved backward upon reaching orbit. This adjustment is needed to cushion the crew members during an inadvertent crash landing situation. JSCs Anthropometry and Biomechanics Facility (ABF) performed an evaluation of the seat controls and provided recommendations on whether the seat lever positions and operations should be modified. The original Shuttle seats were replaced with new lightweight seats whose controls were moved, with one control at the front and the other at the back. The ABF designed a 12-person experiment to investigate the amount of pull force exerted by suited subjects, when controls were placed in the front and back of the lightweight seat. Each subject was asked to perform the pull test at least three times for each combination of lever position and suit pressure conditions. The results showed that, in general, the subjects were able to pull on the lever at the back position with only about half the amount of force that they were able to exert on the lever at the front position. In addition, the results also showed that subjects wearing the pressurized suit were unable to reach the seat lever when it was located at the back. The pull forces on the front lever diminished about 50% when subjects wore pressurized suits. Based on these results from this study, it was recommended that the levers should not be located in the back position. Further investigation is needed to determine whether the levers at the front of the seat could be modified or adjusted to increase the leverage for crew members wearing pressurized launch/escape suits.
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Tomie, Arthur; Festa, Eugene D; Sparta, Dennis R; Pohorecky, Larissa A
2003-05-01
Two experiments were designed to evaluate whether brief access to a saccharin-ethanol solution would function as an effective unconditioned stimulus (US) in Pavlovian-autoshaping procedures. In these experiments, the insertion of a lever conditioned stimulus (CS) was followed by the brief presentation of a sipper tube containing saccharin-ethanol US solution. Experience with this Pavlovian-autoshaping procedure engendered lever CS-directed autoshaping conditioned responses (CRs) in all rats. In Experiment 1, the concentration of ethanol [0%, 2%, 4%, 6%, or 8% (vol./vol.)] in 0.1% saccharin was systematically increased within subjects across autoshaping sessions to evaluate the relation between a rat's drinking and lever pressing. In Experiment 2, the mean intertrial interval (ITI) duration (60, 90, 120 s) was systematically increased within subjects across autoshaping sessions to evaluate the effect of ITI duration on drinking and lever pressing. A pseudoconditioning control group received lever CS randomly with respect to the saccharin-ethanol US solution. In Experiment 1, lever-press autoshaping CRs developed in all rats, and the tendency of a rat to drink an ethanol concentration was predictive of the performance of lever-press autoshaping CRs. In Experiment 2, longer ITIs induced more lever CS-directed responding, and CS-US paired procedures yielded more lever CS-directed responding than that observed in CS-US random procedures. Saccharin-ethanol is an effective US in Pavlovian-autoshaping procedures, inducing more CS-directed responding than in pseudoconditioning controls receiving CS-US random procedures. More lever CS-directed responding was observed when there was more drinking of the saccharin-ethanol US solution (Experiment 1); when the CS and US were paired, rather than random (Experiment 2); and with longer mean ITI durations (Experiment 2). This pattern of results is consistent with the hypothesis that lever CS-directed responding reflects performance of Pavlovian-autoshaping CRs.
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77 FR 68055 - Airworthiness Directives; Bell Helicopter Textron Helicopters
Federal Register 2010, 2011, 2012, 2013, 2014
2012-11-15
... collective lever for a crack, and if there is a crack, before further flight, replacing the collective lever.... The actions are intended to detect a crack in the collective lever, which could lead to failure of the... cracks with a 10X or higher power magnifying glass. If there is a crack in the collective lever paint...
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Autoshaping in micrencephalic rats.
Goldstein, L H; Oakley, D A
1989-06-01
An autoshaping procedure in which the illumination of a lever was predictive of food reinforcement was used to compare learning in rats with micrencephaly induced by irradiation on the 16th day of gestation and in sham-irradiated controls. Both groups showed equivalent levels of lever-directed activity, and the micrencephalic animals differentiated as well as the control animals between the predictive lever and a nonpredictive lever. The micrencephalic animals were able to redistribute their lever-directed activity when the significance of the levers was reversed and did so more readily than the control animals. Results support the claim that association learning survives either traumatic or developmental neocortical damage and have implications for remedial procedures following both head injury and developmental cerebral pathology in humans.
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Chronic pain impairs cognitive flexibility and engages novel learning strategies in rats.
Cowen, Stephen L; Phelps, Caroline E; Navratilova, Edita; McKinzie, David L; Okun, Alec; Husain, Omar; Gleason, Scott D; Witkin, Jeffrey M; Porreca, Frank
2018-03-22
Cognitive flexibility, the ability to adapt behavior to changing outcomes, is critical for survival. The prefrontal cortex is a key site of cognitive control and chronic pain is known to lead to significant morphological changes to this brain region. Nevertheless, the effects of chronic pain on cognitive flexibility and learning remain uncertain. We used an instrumental paradigm to assess adaptive learning in an experimental model of chronic pain induced by tight ligation of the spinal nerves L5/6 (SNL model). Naïve, sham-operated, and SNL rats were trained to perform fixed-ratio, variable-ratio, and contingency-shift behaviors for food reward. Although all groups learned an initial lever-reward contingency, learning was slower in SNL animals in a subsequent choice task that reversed reinforcement contingencies. Temporal analysis of lever-press responses across sessions indicated no apparent deficits in memory consolidation or retrieval. However, analysis of learning within sessions revealed that the lever presses of SNL animals occurred in bursts followed by delays. Unexpectedly, the degree of bursting correlated positively with learning. Under a variable-ratio probabilistic task, SNL rats chose a less profitable behavioral strategy compared to naïve and sham-operated animals. Following extinction of behavior for learned preferences, SNL animals reverted to their initially preferred (i.e., less profitable) behavioral choice. Our data suggest, that in the face of uncertainty, chronic pain drives a preference for familiar associations, consistent with reduced cognitive flexibility. The observed burst-like responding may represent a novel learning strategy in animals with chronic pain.
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Rapidly reconfigurable all-optical universal logic gate
Goddard, Lynford L.; Bond, Tiziana C.; Kallman, Jeffrey S.
2010-09-07
A new reconfigurable cascadable all-optical on-chip device is presented. The gate operates by combining the Vernier effect with a novel effect, the gain-index lever, to help shift the dominant lasing mode from a mode where the laser light is output at one facet to a mode where it is output at the other facet. Since the laser remains above threshold, the speed of the gate for logic operations as well as for reprogramming the function of the gate is primarily limited to the small signal optical modulation speed of the laser, which can be on the order of up to about tens of GHz. The gate can be rapidly and repeatedly reprogrammed to perform any of the basic digital logic operations by using an appropriate analog optical or electrical signal at the gate selection port. Other all-optical functionality includes wavelength conversion, signal duplication, threshold switching, analog to digital conversion, digital to analog conversion, signal routing, and environment sensing. Since each gate can perform different operations, the functionality of such a cascaded circuit grows exponentially.
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ERIC Educational Resources Information Center
McKerchar, Todd L.; Zarcone, Troy J.; Fowler, Stephen C.
2005-01-01
Recent progress in mouse genetics has led to an increased interest in developing procedures for assessing mouse behavior, but relatively few of the behavioral procedures developed involve positively reinforced operant behavior. When operant methods are used, nose poking, not lever pressing, is the target response. In the current study differential…
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The Effects of Lever Arm (Instrument Offset) Error on GRAV-D Airborne Gravity Data
NASA Astrophysics Data System (ADS)
Johnson, J. A.; Youngman, M.; Damiani, T.
2017-12-01
High quality airborne gravity collection with a 2-axis, stabilized platform gravity instrument, such as with a Micro-g LaCoste Turnkey Airborne Gravity System (TAGS), is dependent on the aircraft's ability to maintain "straight and level" flight. However, during flight there is constant rotation about the aircraft's center of gravity. Standard practice is to install the scientific equipment close to the aircraft's estimated center of gravity to minimize the relative rotations with aircraft motion. However, there remain small offsets between the instruments. These distance offsets, the lever arm, are used to define the rigid-body, spatial relationship between the IMU, GPS antenna, and airborne gravimeter within the aircraft body frame. The Gravity for the Redefinition of the American Vertical Datum (GRAV-D) project, which is collecting airborne gravity data across the U.S., uses a commercial software package for coupled IMU-GNSS aircraft positioning. This software incorporates a lever arm correction to calculate a precise position for the airborne gravimeter. The positioning software must do a coordinate transformation to relate each epoch of the coupled GNSS-IMU derived position to the position of the gravimeter within the constantly-rotating aircraft. This transformation requires three inputs: accurate IMU-measured aircraft rotations, GNSS positions, and lever arm distances between instruments. Previous studies show that correcting for the lever arm distances improves gravity results, but no sensitivity tests have been done to investigate how error in the lever arm distances affects the final airborne gravity products. This research investigates the effects of lever arm measurement error on airborne gravity data. GRAV-D lever arms are nominally measured to the cm-level using surveying equipment. "Truth" data sets will be created by processing GRAV-D flight lines with both relatively small lever arms and large lever arms. Then negative and positive incremental errors will be introduced independently in the x, y, and z directions during GPS-IMU processing. Finally, the post-processed gravity data obtained using the erroneous lever arms will be compared to the post-processed truth sets to identify relationships between error in the lever arm measurement and the final gravity product.
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Techniques for establishing schedules with wheel running as reinforcement in rats.
Iversen, I H
1993-07-01
In three experiments, access to wheel running was contingent on lever pressing. In each experiment, the duration of access to running was reduced gradually to 4, 5, or 6 s, and the schedule parameters were expanded gradually. The sessions lasted 2 hr. In Experiment 1, a fixed-ratio 20 schedule controlled a typical break-and-run pattern of lever pressing that was maintained throughout the session for 3 rats. In Experiment 2, a fixed-interval schedule of 6 min maintained lever pressing throughout the session for 3 rats, and for 1 rat, the rate of lever pressing was positively accelerated between reinforcements. In Experiment 3, a variable-ratio schedule of 20 or 35 was in effect and maintained lever pressing at a very stable pace throughout the session for 2 of 3 rats; for 1 rat, lever pressing was maintained at an irregular rate. When the session duration was extended to successive 24-hr periods, with food and water accessible in Experiment 3, lever pressing settled into a periodic pattern occurring at a high rate at approximately the same time each day. In each experiment, the rats that developed the highest local rates of running during wheel access also maintained the most stable and highest rates of lever pressing.
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Erdemir, Ahmet; Piazza, Stephen J
2002-06-01
The lever arm of the ground reaction force (GRF) about the talocrural joint axis is a functionally important indicator of the nature of foot loading. Walking initiation experiments (ten subjects; age, 23-29 years) were completed to demonstrate that rotational foot placement is a possible strategy to specify the lever arm. Externally-rotated foot placement resulted in larger lever arms during push-off. A computer simulation of push-off revealed that a decreased lever arm reduces the plantarflexion moment necessary to maintain a constant forward velocity, while increasing the required plantarflexion velocity. Shortening of the foot thus diminishes the muscular force demand but also requires high muscle fiber shortening velocities that may limit the force generating capacity of plantar flexors. Decreased plantar flexion moment and slow walking previously noted in partial-foot amputees may result from shortened lever arms in this manner.
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Economic substitutability of electrical brain stimulation, food, and water.
Green, L; Rachlin, H
1991-01-01
Concurrent variable-ratio schedules of electrical brain stimulation, food, and water were paired in various combinations as reinforcement of rats' lever presses. Relative prices of the concurrent reinforcers were varied by changing the ratio of the response requirements on the two levers. Economic substitutability, measured by the sensitivity of response ratio to changes in relative price, was highest with brain stimulation reinforcement of presses on both levers and lowest with food reinforcement of presses on one lever and water reinforcement of presses on the other. Substitutability with brain stimulation reinforcement of presses on one lever and either food or water reinforcement for presses on the other was about as high as with brain stimulation for presses on both levers. Electrical brain stimulation for rats may thus serve as an economic substitute for two reinforcers, neither of which is substitutable for the other. PMID:2037823
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Dual resolution, vacuum compatible optical mount
DOE Office of Scientific and Technical Information (OSTI.GOV)
Halpin, John Michael
2011-10-04
An optical mount for an optical element includes a mounting plate, a lever arm pivot coupled to mounting plate, and an adjustment plate. The optical mount also includes a flexure pivot mechanically coupling the adjustment plate to the mounting plate and a lever arm. The optical mount further includes a first adjustment device extending from the adjustment plate to make contact with the lever arm at a first contact point. A projection of a line from the first contact point to a pivot point, measured along the lever arm, is a first predetermined distance. The optical mount additionally includes amore » second adjustment device extending from the adjustment plate to make contact with the lever arm at a second contact point. A projection of a line from the second contact point to the pivot point, measured along the lever arm, is a second predetermined distance greater than the first predetermined distance.« less
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Self-calibration method of the inner lever-arm parameters for a tri-axis RINS
NASA Astrophysics Data System (ADS)
Song, Tianxiao; Li, Kui; Sui, Jie; Liu, Zengjun; Liu, Juncheng
2017-11-01
A rotational inertial navigation system (RINS) could improve navigation performance by modulating the inertial sensor errors with rotatable gimbals. When an inertial measurement unit (IMU) rotates, the deviations between the accelerometer-sensitive points and the IMU center will lead to an inner lever-arm effect. In this paper, a self-calibration method of the inner lever-arm parameters for a tri-axis RINS is proposed. A novel rotation scheme with variable angular rate rotation is designed to motivate the velocity errors caused by the inner lever-arm effect. By extending all inner lever-arm parameters as filter states, a Kalman filter with velocity errors as measurement is established to achieve the calibration. The accuracy and feasibility of the proposed method are illustrated by both simulations and experiments. The final results indicate that the inner lever-arm effect is significantly restrained after compensation by the calibration results.
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Fernández-Lamo, Iván; Sánchez-Campusano, Raudel; Gruart, Agnès; Delgado-García M, José M.
2016-01-01
Proper performance of acquired abilities can be disturbed by the unexpected occurrence of external changes. Rats trained with an operant conditioning task (to press a lever in order to obtain a food pellet) using a fixed-ratio (1:1) schedule were subsequently placed in a Skinner box in which the lever could be removed randomly. Field postsynaptic potentials (fPSPs) were chronically evoked in perforant pathway-hippocampal CA1 (PP-CA1), CA1-subiculum (CA1-SUB), CA1-medial prefrontal cortex (CA1-mPFC), mPFC-nucleus accumbens (mPFC-NAc), and mPFC-basolateral amygdala (mPFC-BLA) synapses during lever IN and lever OUT situations. While lever presses were accompanied by a significant increase in fPSP slopes at the five synapses, the unpredictable absence of the lever were accompanied by decreased fPSP slopes in all, except PP-CA1 synapses. Spectral analysis of local field potentials (LFPs) recorded when the animal approached the corresponding area in the lever OUT situation presented lower spectral powers than during lever IN occasions for all recording sites, apart from CA1. Thus, the unpredictable availability of a reward-related cue modified the activity of cortical and subcortical areas related with the acquisition of operant learning tasks, suggesting an immediate functional reorganization of these neural circuits to address the changed situation and to modify ongoing behaviors accordingly. PMID:27869181
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Lateral, not medial, prefrontal cortex contributes to punishment and aversive instrumental learning
Jean-Richard-dit-Bressel, Philip
2016-01-01
Aversive outcomes punish behaviors that cause their occurrence. The prefrontal cortex (PFC) has been implicated in punishment learning and behavior, although the exact roles for different PFC regions in instrumental aversive learning and decision-making remain poorly understood. Here, we assessed the role of the orbitofrontal (OFC), rostral agranular insular (RAIC), prelimbic (PL), and infralimbic (IL) cortex in instrumental aversive learning and decision-making. Rats that pressed two individually presented levers for pellet rewards rapidly suppressed responding to one lever if it also caused mild punishment (punished lever) but continued pressing the other lever that did not cause punishment (unpunished lever). Inactivations of OFC, RAIC, IL, or PL via the GABA agonists baclofen and muscimol (BM) had no effect on the acquisition of instrumental learning. OFC inactivations increased responding on the punished lever during expression of well-learned instrumental aversive learning, whereas RAIC inactivations increased responding on the punished lever when both levers were presented simultaneously in an unpunished choice test. There were few effects of medial PFC (PL and IL) inactivation. These results suggest that lateral PFC, notably OFC and RAIC, have complementary functions in aversive instrumental learning and decision-making; OFC is important for using established aversive instrumental memories to guide behavior away from actions that cause punishment, whereas RAIC is important for aversive decision-making under conditions of choice. PMID:27918280
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Belke, Terry W; Pierce, W David
2009-02-01
Twelve female Long-Evans rats were exposed to concurrent variable (VR) ratio schedules of sucrose and wheel-running reinforcement (Sucrose VR 10 Wheel VR 10; Sucrose VR 5 Wheel VR 20; Sucrose VR 20 Wheel VR 5) with predetermined budgets (number of responses). The allocation of lever pressing to the sucrose and wheel-running alternatives was assessed at high and low body weights. Results showed that wheel-running rate and lever-pressing rates for sucrose and wheel running increased, but the choice of wheel running decreased at the low body weight. A regression analysis of relative consumption as a function of relative price showed that consumption shifted toward sucrose and interacted with price differences in a manner consistent with increased substitutability. Demand curves showed that demand for sucrose became less elastic while demand for wheel running became more elastic at the low body weight. These findings reflect an increase in the difference in relative value of sucrose and wheel running as body weight decreased. Discussion focuses on the limitations of response rates as measures of reinforcement value. In addition, we address the commonalities between matching and demand curve equations for the analysis of changes in relative reinforcement value.
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Effects of lesions of the amygdala central nucleus on autoshaped lever pressing
Chang, Stephen E.; Wheeler, Daniel S.; Holland, Peter C.
2012-01-01
Neutral cues paired with rewards often appear to acquire motivational significance, as if the incentive motivational value of the reward is transferred to the cue. Such cues have been reported to modulate the performance of instrumental action (Pavlovian-instrumental transfer, PIT), serve as conditioned reinforcers in the establishment of new learning, and be the targets of approach and other cue-directed behaviors. Here we examined the effects of lesions of the amygdala central nucleus (CeA) on the acquisition of discriminative autoshaped lever-pressing. Insertion of one lever into the experimental chamber was reinforced by sucrose delivery, but insertion of another lever was not reinforced. Although sucrose delivery was not contingent on lever pressing, both CeA- and sham-lesioned rats rapidly came to press the reinforced but not the nonreinforced lever. Despite their showing little evidence of impairments in autoshaped lever pressing, these same CeA-lesioned rats showed significant deficits in the expression of PIT in a subsequent phase of the experiment. The lack of impaired autoshaping in CeA-lesioned rats contrasts with effects previously reported for conditioned orienting responses (ORs) and for other putative measures of incentive learning including PIT and conditioned approach to visual cues. PMID:22386516
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Parallel learning in an autoshaping paradigm.
Naeem, Maliha; White, Norman M
2016-08-01
In an autoshaping task, a single conditioned stimulus (CS; lever insertion) was repeatedly followed by the delivery of an unconditioned stimulus (US; food pellet into an adjacent food magazine) irrespective of the rats' behavior. After repeated training trials, some rats responded to the onset of the CS by approaching and pressing the lever (sign-trackers). Lesions of dorsolateral striatum almost completely eliminated responding to the lever CS while facilitating responding to the food magazine (US). Lesions of the dorsomedial striatum attenuated but did not eliminate responding to the lever CS. Lesions of the basolateral or central nucleus of the amygdala had no significant effects on sign-tracking, but combined lesions of the 2 structures impaired sign-tracking by significantly increasing latency to the first lever press without affecting the number of lever presses. Lesions of the dorsal hippocampus had no effect on any of the behavioral measures. The findings suggest that sign-tracking with a single lever insertion as the CS may consist of 2 separate behaviors learned in parallel: An amygdala-mediated conditioned orienting and approach response and a dorsal striatum-mediated instrumental response. (PsycINFO Database Record (c) 2016 APA, all rights reserved).
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Orsini, Caitlin A; Trotta, Rose T; Bizon, Jennifer L; Setlow, Barry
2015-01-28
Several neuropsychiatric disorders are associated with abnormal decision-making involving risk of punishment, but the neural basis of this association remains poorly understood. Altered activity in brain systems including the basolateral amygdala (BLA) and orbitofrontal cortex (OFC) can accompany these same disorders, and these structures are implicated in some forms of decision-making. The current study investigated the role of the BLA and OFC in decision-making under risk of explicit punishment. Rats were trained in the risky decision-making task (RDT), in which they chose between two levers, one that delivered a small safe reward, and the other that delivered a large reward accompanied by varying risks of footshock punishment. Following training, they received sham or neurotoxic lesions of BLA or OFC, followed by RDT retesting. BLA lesions increased choice of the large risky reward (greater risk-taking) compared to both prelesion performance and sham controls. When reward magnitudes were equated, both BLA lesion and control groups shifted their choice to the safe (no shock) reward lever, indicating that the lesions did not impair punishment sensitivity. In contrast to BLA lesions, OFC lesions significantly decreased risk-taking compared with sham controls, but did not impair discrimination between different reward magnitudes or alter baseline levels of anxiety. Finally, neither lesion significantly affected food-motivated lever pressing under various fixed ratio schedules, indicating that lesion-induced alterations in risk-taking were not secondary to changes in appetitive motivation. Together, these findings indicate distinct roles for the BLA and OFC in decision-making under risk of explicit punishment. Copyright © 2015 the authors 0270-6474/15/351368-12$15.00/0.
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Mohler, Eric G; Franklin, Stanley R; Rueter, Lynne E
2014-01-01
Neuronal α4β2* nicotinic acetylcholine receptors mediate cognition, pain, and the discriminative and reinforcing effects of nicotine. In addition to traditional orthosteric agonists, α4β2* positive allosteric modulators (PAMs) have recently been identified. With increased subtype selectivity relative to agonists, PAMs administered alone or in combination with low-dose α4β2* agonists may be used as powerful tools for increasing our understanding of α4β2* pharmacology. The present experiments tested the nicotine discriminative-stimulus effects of the α4β2* PAM NS9283 (A-969933) in the presence and absence of low-dose nicotine or nicotinic subtype-selective agonist. Rats were trained to discriminate 0.4 mg/kg nicotine from saline in a two-lever drug discrimination paradigm. In subsequent generalization tests, rats were administered nicotine, the α4β2*-preferring agonist ABT-594, and NS9283, alone or in two-drug combinations. Nicotine and ABT-594 showed dose-dependent nicotine generalization. NS9283 alone resulted in a non-significant increase in nicotine-appropriate lever selection. Combination of non-effective doses of nicotine or ABT-594 with escalating doses of NS9283 resulted in a complete conversion to 100 % nicotine-appropriate choice in the case of nicotine combination and incomplete, though significant, generalization for ABT-594. The α4β2* PAM NS9283 alone did not produce nicotine-like discriminative effects, but did demonstrate dose-related increases in nicotine lever choice when combined with a non-effective dose of nicotine or the α4β2* agonist ABT-594. This finding provides confirmation of the positive allosteric modulating effect of NS9283 in a functional in vivo paradigm. NS9283 is a potentially valuable tool for studying the role of α4β2* receptors in various nicotinic acetylcholine receptor-related functions.
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Apparatus for Teaching Physics.
ERIC Educational Resources Information Center
Minnix, Richard B., Ed.; Carpenter, D. Rae, Jr., Ed.
1983-01-01
Describes four body-lever models (biceps, triceps, back lever when lifting, foot lever and Achilles tendon muscle) used in noncalculus physics courses. Instructions for constructing the wooden models are provided. Also describes an improvement on a centripetal-force apparatus so that it is easier to operate. (JN)
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Switch Using Radio Frequency Identification
NASA Technical Reports Server (NTRS)
Fink, Patrick W. (Inventor); Kennedy, Timothy F. (Inventor); Lin, Gregory Y. (Inventor); Ngo, Phong H. (Inventor)
2015-01-01
Disclosed is an apparatus for use as a switch. In one embodiment, the switch comprises at least one RFID tag, each RFID tag comprising an antenna element and an RFID integrated circuit, at least one source element, and at least one lever arm. Each lever arm is connected to one of the RFID tags, and each lever arm is capable of two positions. One of the positions places the lever arm and the RFID tag connected thereto into alignment with the source element. Other embodiments are also described.
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Code of Federal Regulations, 2013 CFR
2013-10-01
... 49 Transportation 4 2013-10-01 2013-10-01 false Electromechanical interlocking machine; locking between electrical and mechanical levers. 236.340 Section 236.340 Transportation Other Regulations... Electromechanical interlocking machine; locking between electrical and mechanical levers. In electro-mechanical...
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Code of Federal Regulations, 2014 CFR
2014-10-01
... 49 Transportation 4 2014-10-01 2014-10-01 false Electromechanical interlocking machine; locking between electrical and mechanical levers. 236.340 Section 236.340 Transportation Other Regulations... Electromechanical interlocking machine; locking between electrical and mechanical levers. In electro-mechanical...
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Code of Federal Regulations, 2012 CFR
2012-10-01
... 49 Transportation 4 2012-10-01 2012-10-01 false Electromechanical interlocking machine; locking between electrical and mechanical levers. 236.340 Section 236.340 Transportation Other Regulations... Electromechanical interlocking machine; locking between electrical and mechanical levers. In electro-mechanical...
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Code of Federal Regulations, 2011 CFR
2011-10-01
... 49 Transportation 4 2011-10-01 2011-10-01 false Electromechanical interlocking machine; locking between electrical and mechanical levers. 236.340 Section 236.340 Transportation Other Regulations... Electromechanical interlocking machine; locking between electrical and mechanical levers. In electro-mechanical...
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The matching law in and within groups of rats1
Graft, D. A.; Lea, S. E. G.; Whitworth, T. L.
1977-01-01
In each of the two experiments, a group of five rats lived in a complex maze containing four small single-lever operant chambers. In two of these chambers, food was available on variable-interval schedules of reinforcement. In Experiment I, nine combinations of variable intervals were used, and the aggregate lever-pressing rates (by the five rats together) were studied. The log ratio of the rates in the two chambers was linearly related to the log ratio of the reinforcement rates in them; this is an instance of Herrnstein's matching law, as generalized by Baum. Summing over the two food chambers, food consumption decreased, and response output increased, as the time required to earn each pellet increased. In Experiment II, the behavior of individual rats was observed by time-sampling on selected days, while different variable-interval schedules were arranged in the two chambers where food was available. Individual lever-pressing rates for the rats were obtained, and their median bore the same “matching” relationship to the reinforcement rates as the group aggregate in Experiment I. There were differences between the rats in their distribution of time and responses between the two food chambers; these differences were correlated with differences in the proportions of reinforcements the rats obtained from each chamber. PMID:16811975
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Aversive properties of negative incentive shifts in Fischer 344 and Lewis rats
Brewer, Adam; Johnson, Patrick; Stein, Jeff; Schlund, Michael; Williams, Dean C.
2018-01-01
Research on incentive contrast highlights that reward value is not absolute but rather is based upon comparisons we make to rewards we have received and expect to receive. Both human and nonhuman studies on incentive contrast show that shifting from a larger more-valued reward to a smaller less-valued reward is associated with long periods of nonresponding—a negative contrast effect. In this investigation, we used two different genetic rat strains, Fischer 344 and Lewis rats that putatively differ in their sensitivity to aversive stimulation, to assess the aversive properties of large-to-small reward shifts (negative incentive shifts). Additionally, we examined the extent to which increasing cost (fixed-ratio requirements) modulates negative contrast effects. In the presence of a cue that signaled the upcoming reward magnitude, lever pressing was reinforced with one of two different magnitudes of food (large or small). This design created two contrast shifts (small-to-large, large-to-small) and two shifts used as control conditions (small-to-small, large-to-large). Results showed a significant interaction between rat strain and cost requirements only during the negative incentive shift with the emotionally reactive Fischer 344 rats exhibiting significantly longer response latencies with increasing cost, highlighting greater negative contrast. These findings are more consistent with emotionality accounts of negative contrast and results of neurophysiological research that suggests shifting from a large to a small reward is aversive. Findings also highlight how subjective reward value and motivation is a product of gene-environment interactions. PMID:27864048
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Cost of Oil and Biomass Supply Shocks under Different Biofuel Supply Chain Configurations
DOE Office of Scientific and Technical Information (OSTI.GOV)
Uria Martinez, Rocio; Leiby, Paul Newsome; Brown, Maxwell L.
This analysis estimates the cost of selected oil and biomass supply shocks for producers and consumers in the light-duty vehicle fuel market under various supply chain configurations using a mathematical programing model, BioTrans. The supply chain configurations differ by whether they include selected flexibility levers: multi-feedstock biorefineries; advanced biomass logistics; and the ability to adjust ethanol content of low-ethanol fuel blends, from E10 to E15 or E05. The simulated scenarios explore market responses to supply shocks including substitution between gasoline and ethanol, substitution between different sources of ethanol supply, biorefinery capacity additions or idling, and price adjustments. Welfare effects formore » the various market participants represented in BioTrans are summarized into a net shock cost measure. As oil accounts for a larger fraction of fuel by volume, its supply shocks are costlier than biomass supply shocks. Corn availability and the high cost of adding biorefinery capacity limit increases in ethanol use during gasoline price spikes. During shocks that imply sudden decreases in the price of gasoline, the renewable fuel standard (RFS) biofuel blending mandate limits the extent to which flexibility can be exercised to reduce ethanol use. The selected flexibility levers are most useful in response to cellulosic biomass supply shocks.« less
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Zaru, Alessandro; Maccioni, Paola; Colombo, Giancarlo; Gessa, Gian Luigi
2013-10-01
Craving for chocolate is a common phenomenon, which may evolve to an addictive-like behaviour and contribute to obesity. Nepicastat is a selective dopamine β-hydroxylase (DBH) inhibitor that suppresses cocaine-primed reinstatement of cocaine seeking in rats. We verified whether nepicastat was able to modify the reinforcing and motivational properties of a chocolate solution and to prevent the reinstatement of chocolate seeking in rats. Nepicastat (25, 50 and 100 mg/kg, intraperitoneal) produced a dose-related inhibition of operant self-administration of the chocolate solution in rats under fixed-ratio 10 (FR10) and progressive-ratio schedules of reinforcement, measures of the reinforcing and motivational properties of the chocolate solution, respectively. The effect of nepicastat on the reinstatement of chocolate seeking was studied in rats in which lever-responding had been extinguished by removing the chocolate solution for approximately 8 d. Nepicastat dose-dependently suppressed the reinstatement of lever-responding triggered by a 'priming' of the chocolate solution together with cues previously associated with the availability of the reward. In a separate group of food-restricted rats trained to lever-respond for regular food pellets, nepicastat reduced FR10 lever-responding with the same potency as for the chocolate solution. Spontaneous locomotor activity was not modified by nepicastat doses that reduced self-administration of the chocolate solution and regular food pellets and suppressed the reinstatement of chocolate seeking. The results indicate that nepicastat reduces motivation to food consumption sustained by appetite or palatability. Moreover, the results suggest that DBH inhibitors may be a new class of pharmacological agents potentially useful in the prevention of relapse to food seeking in human dieters.
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Maccioni, Paola; Flore, Paolo; Carai, Mauro A. M.; Mugnaini, Claudia; Pasquini, Serena; Corelli, Federico; Gessa, Gian Luigi; Colombo, Giancarlo
2010-01-01
The present study was designed to evaluate (a) alcohol self-administration behavior of selectively bred, Sardinian alcohol-preferring (sP) rats exposed to the so-called “sipper” procedure (characterized by the temporal separation between alcohol-seeking and -taking phases), and (b) the effect of the positive allosteric modulator of the GABAB receptor, GS39783, on alcohol self-administration in sP rats exposed to this procedure. To this end, sP rats were initially trained to lever-respond under a reinforcement requirement (RR) 55 (RR55) for alcohol. Achievement of RR55 resulted in the 20-min presentation of the alcohol (15%, v/v)-containing sipper bottle. Once stable levels of lever-responding and alcohol consumption were reached, rats were treated with 0, 25, 50, and 100 mg/kg GS39783 (i.g.) 60 min before the self-administration session. Rats displayed robust alcohol-seeking (as suggested by relatively short latencies to the first lever-response and high frequencies of lever-responding) and -taking (as suggested by alcohol intakes averaging approximately 1.5 g/kg) behaviors. Pretreatment with GS39783 inhibited both alcohol-seeking (the number of rats achieving RR55 and the mean RR value were virtually halved) and -taking (the amount of self-administered alcohol was reduced by approximately 60%). The results of the present study suggest the power of the “sipper” procedure in triggering high levels of alcohol-seeking and -taking behavior in sP rats. Further, these results extend to this additional procedure of alcohol self-administration the capacity of GS39783 to reduce the motivational properties of alcohol and alcohol consumption in sP rats. PMID:21423431
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Baladi, Michelle G; Newman, Amy H; France, Charles P
2014-02-01
The contribution of dopamine receptor subtypes in mediating the discriminative stimulus effects of cocaine is not fully established. Many drug discrimination studies use food to maintain responding, necessitating food restriction, which can alter drug effects. This study established stimulus control with cocaine (10 mg/kg) in free-feeding and food-restricted rats responding under a schedule of stimulus shock termination (SST) and in food-restricted rats responding under a schedule of food presentation to examine whether feeding condition or the reinforcer used to maintain responding impacts the effects of cocaine. Dopamine receptor agonists and antagonists were examined for their ability to mimic or attenuate, respectively, the effects of cocaine. Apomorphine, quinpirole, and lisuride occasioned >90 % responding on the cocaine-associated lever in free-feeding rats responding under a schedule of SST; apomorphine, but not quinpirole or lisuride, occasioned >90 % responding on the cocaine lever in food-restricted rats responding under a schedule of SST. In food-restricted rats responding for food these drugs occasioned little cocaine lever responding and were comparatively more potent in decreasing responding. In free-feeding rats, the effects of cocaine were attenuated by the D2/D3 receptor antagonist raclopride and the D3 receptor-selective antagonist PG01037. In food-restricted rats, raclopride and the D2 receptor-selective antagonist L-741,626 attenuated the effects of cocaine. Raclopride antagonized quinpirole in all groups while PG01037 antagonized quinpirole only in free-feeding rats. These results demonstrate significant differences in the discriminative stimulus of cocaine that are due to feeding conditions and not to the use of different reinforcers across procedures.
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Baladi, Michelle G; Newman, Amy H; France, Charles P
2013-01-01
Rationale The contribution of dopamine receptor subtypes in mediating the discriminative stimulus effects of cocaine is not fully established. Many drug discrimination studies use food to maintain responding, necessitating food restriction, which can alter drug effects. Objective This study established stimulus control with cocaine (10 mg/kg) in free-feeding and food-restricted rats responding under a schedule of stimulus shock termination (SST) and in food-restricted rats responding under a schedule of food presentation to examine whether feeding condition or the reinforcer used to maintain responding impacts the effects of cocaine. Method Dopamine receptor agonists and antagonists were examined for their ability to mimic or attenuate, respectively, the effects of cocaine. Result Apomorphine, quinpirole, and lisuride occasioned >90% responding on the cocaine-associated lever in free-feeding rats responding under a schedule of SST; apomorphine, but not quinpirole or lisuride, occasioned >90% responding on the cocaine lever in food-restricted rats responding under a schedule of SST. In food-restricted rats responding for food these drugs occasioned little cocaine lever responding and were comparatively more potent in decreasing responding. In free-feeding rats, the effects of cocaine were attenuated by the D2/D3 receptor antagonist raclopride and the D3 receptor-selective antagonist PG01037. In food-restricted rats, raclopride and the D2 receptor-selective antagonist L-741,626 attenuated the effects of cocaine. Raclopride antagonized quinpirole in all groups while PG01037 antagonized quinpirole only in free-feeding rats. Conclusion These results demonstrate significant differences in the discriminative stimulus of cocaine that are due to feeding conditions and not to the use of different reinforcers across procedures. PMID:24030470
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Parkinson, J A; Olmstead, M C; Burns, L H; Robbins, T W; Everitt, B J
1999-03-15
Dopamine release within the nucleus accumbens (NAcc) has been associated with both the rewarding and locomotor-stimulant effects of abused drugs. The functions of the NAcc core and shell were investigated in mediating amphetamine-potentiated conditioned reinforcement and locomotion. Rats were initially trained to associate a neutral stimulus (Pavlovian CS) with food reinforcement (US). After excitotoxic lesions that selectively destroyed either the NAcc core or shell, animals underwent additional CS-US training sessions and then were tested for the acquisition of a new instrumental response that produced the CS acting as a conditioned reinforcer (CR). Animals were infused intra-NAcc with D-amphetamine (0, 1, 3, 10, or 20 microg) before each session. Shell lesions affected neither Pavlovian nor instrumental conditioning but completely abolished the potentiative effect of intra-NAcc amphetamine on responding with CR. Core-lesioned animals were impaired during the Pavlovian retraining sessions but showed no deficit in the acquisition of responding with CR. However, the selectivity in stimulant-induced potentiation of the CR lever was reduced, as intra-NAcc amphetamine infusions dose-dependently increased responding on both the CR lever and a nonreinforced (control) lever. Shell lesions produced hypoactivity and attenuated amphetamine-induced activity. In contrast, core lesions resulted in hyperactivity and enhanced the locomotor-stimulating effect of amphetamine. These results indicate a functional dissociation of subregions of the NAcc; the shell is a critical site for stimulant effects underlying the enhancement of responding with CR and locomotion after intra-NAcc injections of amphetamine, whereas the core is implicated in mechanisms underlying the expression of CS-US associations.
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Hafenbreidel, Madalyn; Rafa Todd, Carolynn; Mueller, Devin
2017-04-01
Addiction is characterized by high relapse susceptibility, and relapse can be triggered by drug-associated cues. Cue presentation induces retrieval of the drug-cue memory, which becomes labile and must be reconsolidated into long-term storage. Repeated unpaired cue presentation, however, promotes extinction. Cue-reactivity can be reduced by blocking reconsolidation or facilitating extinction, which are mediated by NMDA receptors (NMDArs). However, the role of NMDArs in either process following self-administration is unclear. Thus, to determine their role in extinction, rats learned to self-administer cocaine before receiving injections of the NMDAr antagonist CPP immediately after four 45-min extinction sessions. During a subsequent 90-min extinction retention test, CPP-treated rats lever pressed less than saline-treated rats indicating that NMDAr blockade facilitated extinction or disrupted drug-cue memory reconsolidation. In addition, infusing CPP into the infralimbic medial prefrontal cortex (IL-mPFC), a structure implicated in extinction, before four 45-min or immediately after four 30min extinction sessions, had similar results during the extinction retention tests. Next, the GluN2A-selective antagonist NVP or GluN2B-selective antagonist Ro25 was infused into IL-mPFC or nucleus accumbens (NAc) shell, another structure implicated in extinction, after four 45-min extinction sessions. Blocking GluN2A-, but not GluN2B-, containing NMDArs, in IL-mPFC or NAc shell reduced lever pressing during the extinction retention tests. Finally, to dissociate reconsolidation from extinction, NVP was infused into IL-mPFC after four 10-min reactivation sessions, which resulted in reduced lever pressing during the retention test. These results indicate that IL-mPFC GluN2A-containing NMDArs modulate reconsolidation, and suggest a novel treatment strategy, as reducing cue reactivity could limit relapse susceptibility.
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College Enrollment and Completion among Nationally Recognized High-Achieving Hispanic Students
ERIC Educational Resources Information Center
Gurantz, Oded; Hurwitz, Michael; Smith, Jonathan
2017-01-01
Hispanic high school graduates have lower college completion rates than academically similar white students. As Hispanic students have been theorized to be more constrained in the college search and selection process, one potential policy lever is to increase the set of colleges to which these students apply and attend. In this paper, we…
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Zhou, Bin; Yang, Rui; Li, Canbing
Here, time-of-use (TOU) rates and stepwise power tariff (SPT) are important economic levers to motivate residents to shift their electricity usage in response to electricity price. In this paper, a new multiobjective optimal tariff-making model of time-of-use and stepwise power tariff (TOUSPT) is proposed, which combines the complementary characteristics of two power tariffs, for residential energy conservation and peak load shaving. In the proposed approach, the residential demand response with price elasticity in regulated power market is considered to determine the optimum peak-valley TOU tariffs for each stepwise electricity partition. Furthermore, a practical case study is implemented to test themore » effectiveness of the proposed TOUSPT, and the results demonstrate that TOUSPT can achieve efficient end-use energy saving and also shift load from peak to off-peak periods.« less
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Zhou, Bin; Yang, Rui; Li, Canbing; ...
2017-07-04
Here, time-of-use (TOU) rates and stepwise power tariff (SPT) are important economic levers to motivate residents to shift their electricity usage in response to electricity price. In this paper, a new multiobjective optimal tariff-making model of time-of-use and stepwise power tariff (TOUSPT) is proposed, which combines the complementary characteristics of two power tariffs, for residential energy conservation and peak load shaving. In the proposed approach, the residential demand response with price elasticity in regulated power market is considered to determine the optimum peak-valley TOU tariffs for each stepwise electricity partition. Furthermore, a practical case study is implemented to test themore » effectiveness of the proposed TOUSPT, and the results demonstrate that TOUSPT can achieve efficient end-use energy saving and also shift load from peak to off-peak periods.« less
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40 CFR 1065.310 - Torque calibration.
Code of Federal Regulations, 2014 CFR
2014-07-01
... force is measured. The lever arm must be perpendicular to gravity (i.e., horizontal), and it must be... known distance along a lever arm. Make sure the weights' lever arm is perpendicular to gravity (i.e... Earth's gravity, as described in § 1065.630. Calculate the reference torque as the weights' reference...
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Contingency Tracking during Unsignaled Delayed Reinforcement
ERIC Educational Resources Information Center
Keely, Josue; Feola, Tyler; Lattal, Kennon A.
2007-01-01
Three experiments were conducted with rats in which responses on one lever (labeled the functional lever) produced reinforcers after an unsignaled delay period that reset with each response during the delay. Responses on a second, nonfunctional, lever did not initiate delays, but, in the first and third experiments, such responses during the last…
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40 CFR 1065.310 - Torque calibration.
Code of Federal Regulations, 2013 CFR
2013-07-01
... reference force is measured. The lever arm must be perpendicular to gravity (i.e., horizontal), and it must... known distance along a lever arm. Make sure the weights' lever arm is perpendicular to gravity (i.e... gravity (using this equation: force = mass · acceleration). The local acceleration of gravity, a g, at...
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40 CFR 1065.310 - Torque calibration.
Code of Federal Regulations, 2012 CFR
2012-07-01
... reference force is measured. The lever arm must be perpendicular to gravity (i.e., horizontal), and it must... known distance along a lever arm. Make sure the weights' lever arm is perpendicular to gravity (i.e... gravity (using this equation: force = mass · acceleration). The local acceleration of gravity, a g, at...
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NASA Astrophysics Data System (ADS)
Wang, Tongda; Cheng, Jianhua; Guan, Dongxue; Kang, Yingyao; Zhang, Wei
2017-09-01
Due to the lever-arm effect and flexural deformation in the practical application of transfer alignment (TA), the TA performance is decreased. The existing polar TA algorithm only compensates a fixed lever-arm without considering the dynamic lever-arm caused by flexural deformation; traditional non-polar TA algorithms also have some limitations. Thus, the performance of existing compensation algorithms is unsatisfactory. In this paper, a modified compensation algorithm of the lever-arm effect and flexural deformation is proposed to promote the accuracy and speed of the polar TA. On the basis of a dynamic lever-arm model and a noise compensation method for flexural deformation, polar TA equations are derived in grid frames. Based on the velocity-plus-attitude matching method, the filter models of polar TA are designed. An adaptive Kalman filter (AKF) is improved to promote the robustness and accuracy of the system, and then applied to the estimation of the misalignment angles. Simulation and experiment results have demonstrated that the modified compensation algorithm based on the improved AKF for polar TA can effectively compensate the lever-arm effect and flexural deformation, and then improve the accuracy and speed of TA in the polar region.
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Jordan, Chloe J.; Taylor, Danielle M.; Dwoskin, Linda P.; Kantak, Kathleen M.
2015-01-01
Attention-deficit/hyperactivity disorder (ADHD) is comorbid with cocaine abuse. Whereas initiating ADHD medication in childhood does not alter later cocaine abuse risk, initiating medication during adolescence may increase risk. Preclinical work in the Spontaneously Hypertensive Rat (SHR) model of ADHD found that adolescent methylphenidate increased cocaine self-administration in adulthood, suggesting a need to identify alternatively efficacious medications for teens with ADHD. We examined effects of adolescent d-amphetamine treatment on strategy set shifting performance during adolescence and on cocaine self-administration and reinstatement of cocaine-seeking behavior (cue reactivity) during adulthood in male SHR, Wistar-Kyoto (inbred control), and Wistar (outbred control) rats. During the set shift phase, adolescent SHR needed more trials and had a longer latency to reach criterion, made more regressive errors and trial omissions, and exhibited slower and more variable lever press reaction times. d-Amphetamine improved performance only in SHR by increasing choice accuracy and decreasing errors and latency to criterion. In adulthood, SHR self-administered more cocaine, made more cocaine-seeking responses, and took longer to extinguish lever responding than control strains. Adolescent d-amphetamine did not alter cocaine self-administration in adult rats of any strain, but reduced cocaine seeking during the first of seven reinstatement test sessions in adult SHR. These findings highlight utility of SHR in modeling cognitive dysfunction and comorbid cocaine abuse in ADHD. Unlike methylphenidate, d-amphetamine improved several aspects of flexible learning in adolescent SHR and did not increase cocaine intake or cue reactivity in adult SHR. Thus, adolescent d-amphetamine was superior to methylphenidate in this ADHD model. PMID:26467602
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Federal Register 2010, 2011, 2012, 2013, 2014
2010-08-12
.... Section 105 of AREERA amended the Smith-Lever Act to require that a specified amount of agricultural... Hatch Act and Smith-Lever Act to require that a specified amount of agricultural research and extension... Smith- Lever Act funds on multistate extension activities and 25 percent on integrated research and...
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NASA Astrophysics Data System (ADS)
Anggraini, L.; Sugeng
2018-05-01
This research discusses the testing and analysis of cracking Aluminum (Al) material. Al as a handle lever was used for a braking device on a motor vehicle. Cracking of handle lever due to the part content of porosity from hydrogen gas. The existence of the H2 can be caused by the casting process and dies design that is less perfect, especially at the gate or brisket and overflow. This research is to optimize the process of making Al part handle lever, and the construction dies by following the standard. The results of these improvements were reevaluated through the chemical and mechanical testing properties stages, such as density test and tensile test on the workpiece as part handle lever. The loads on the tensile test are 25 kg and 35 kg, and the tensile test result has met the standard set by the motor vehicle company. The optimization result has the porosity defect can be reduced by 99 %. Therefore the best part handle lever can be produced.
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Atnip, G W
1977-07-01
Separate groups of rats received 500 trials of lever-press training under autoshaping (food delivery followed 10-second lever presentations, or occurred immediately following a response); operant conditioning (responding was necessary for food delivery); and classical conditioning (food followed lever presentations regardless of responding). Each group then received 500 trials on an omission procedure in which food was omitted on trials with a response. Another group received 1000 trials on the omission procedure, and a fifth group, random control, received 1000 uncorrelated presentations of lever and food. The autoshaping, operant, and classical groups reached high response levels by the end of initial training. Acquisition was fastest in the autoshaping group. Responding remained consistently low in the control group. The omission group responded at a level between the control group and the other three groups. During omission training, responding in these three groups declined to the omission-group level. During omission training, the rats continued contacting the lever frequently after lever pressing had declined. Response maintenance under omission training seems not to require topographic similarity between the response and reinforcer-elicited consummatory behaviors.
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Atnip, Gilbert W.
1977-01-01
Separate groups of rats received 500 trials of lever-press training under autoshaping (food delivery followed 10-second lever presentations, or occurred immediately following a response); operant conditioning (responding was necessary for food delivery); and classical conditioning (food followed lever presentations regardless of responding). Each group then received 500 trials on an omission procedure in which food was omitted on trials with a response. Another group received 1000 trials on the omission procedure, and a fifth group, random control, received 1000 uncorrelated presentations of lever and food. The autoshaping, operant, and classical groups reached high response levels by the end of initial training. Acquisition was fastest in the autoshaping group. Responding remained consistently low in the control group. The omission group responded at a level between the control group and the other three groups. During omission training, responding in these three groups declined to the omission-group level. During omission training, the rats continued contacting the lever frequently after lever pressing had declined. Response maintenance under omission training seems not to require topographic similarity between the response and reinforcer-elicited consummatory behaviors. PMID:16812014
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Torque-Limiting Infinitely-Variable CAM Release Mechanism for a Rotatable Joint
NASA Technical Reports Server (NTRS)
Moetteli, John B. (Inventor)
1997-01-01
The invention relates to a mechanism for permitting convenient manual or servo-powered control of a boom assembly, which is rotatably positionable about yaw and pitch axes by means of releasably locking, yaw and pitch torque-limiting mechanisms, each of which may be locked, unlocked, and positioned by respective yaw and pitch levers. The boom may be longitudinally projected and withdrawn by rotating a boom extension/retraction crank. Torque limiting is provided by spring loaded clutch mechanisms, whereby positioning forces applied to the handles are effective to move the boom unless overcome by greater opposing forces, sufficient to overcome the torque applied by the torque limiting clutch mechanisms. In operation, a structure positionable by the invention (e.g., and end-effector or robot arm) may be rotatably moved about yaw and pitch axes by moving a selected one of the three levers.
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Bryan, Myranda A.; Popov, Pavlo; Scarff, Raymond; Carter, Cody; Wright, Erin; Aragona, Brandon J.; Robinson, Terry E.
2016-01-01
The sensory properties of a reward-paired cue (a conditioned stimulus; CS) may impact the motivational value attributed to the cue, and in turn influence the form of the conditioned response (CR) that develops. A cue with multiple sensory qualities, such as a moving lever-CS, may activate numerous neural pathways that process auditory and visual information, resulting in CRs that vary both within and between individuals. For example, CRs include approach to the lever-CS itself (rats that “sign-track”; ST), approach to the location of reward delivery (rats that “goal-track”; GT), or an “intermediate” combination of these behaviors. We found that the multimodal sensory features of the lever-CS were important to the development and expression of sign-tracking. When the lever-CS was covered, and thus could only be heard moving, STs not only continued to approach the lever location but also started to approach the food cup during the CS period. While still predictive of reward, the auditory component of the lever-CS was a much weaker conditioned reinforcer than the visible lever-CS. This plasticity in behavioral responding observed in STs closely resembled behaviors normally seen in rats classified as “intermediates.” Furthermore, the ability of both the lever-CS and the reward-delivery to evoke dopamine release in the nucleus accumbens was also altered by covering the lever—dopamine signaling in STs resembled neurotransmission observed in rats that normally only GT. These data suggest that while the visible lever-CS was attractive, wanted, and had incentive value for STs, when presented in isolation, the auditory component of the cue was simply predictive of reward, lacking incentive salience. Therefore, the specific sensory features of cues may differentially contribute to responding and ensure behavioral flexibility. PMID:27918279
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16. OPERATOR STAND. OPERATOR STOOD BETWEEN RAILINGS AND CONTROLLED DREDGING ...
16. OPERATOR STAND. OPERATOR STOOD BETWEEN RAILINGS AND CONTROLLED DREDGING OPERATIONS USING TWO LEVERS FROM CEILING, THREE LEVELS ON THE FLOOR, AND TWO FLOOR PEDDLES. RIGHT HAND CONTROLLED SHOT GUN SWINGER (BOOM MOVE TO RIGHT WHEN PUSHED FORWARD, LEFT WHEN PULLED BACK, AND, IF LUCKY, STOPPED WHEN IN CENTER POSITION). LEFT HAND CONTROLLED THROTTLE. FLOOR LEVER AND FLOOR PEDDLE ON LEFT CONTROLLED THE BACKING LINE FRICTION. MIDDLE LEVER AND PEDDLE, STUCK IN FLOOR CONTROLLED THE MAIN HOIST FRICTION. LEVER ON RIGHT CONTROLLED THE CYLINDER DRAIN VALVE. - Dredge CINCINNATI, Docked on Ohio River at foot of Lighthill Street, Pittsburgh, Allegheny County, PA
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Ergonomic Evaluation of Space Shuttle Light-Weight Seat Lever Position and Operation
NASA Technical Reports Server (NTRS)
Maida, J.; Rajulu, Sudhakar L.; Bond, Robert L. (Technical Monitor)
2000-01-01
During a Shuttle flight in the early part of 1999, one of the crewmembers was unable to operate the backrest lever for the light-weight seat in microgravity. It is essential that the crewmembers are able to adjust this back-rest lever, which is titled forward 2 degrees from vertical during launch and then moved backwards to 10 degrees aft of vertical upon reaching orbit. This adjustment is needed to cushion the crewmembers during an inadvertent crash landing situation. The original Shuttle seats, which had seat controls located on the front left and right sides of the seat, were replaced recently with the new light-weight seats. The controls for these new, seats were moved to the night side with one control at the front and the other at the back. While it was uncertain whether the problem encountered was unique to that crewmember or not it was clear to the personnel responsible for maintaining the Shuttle seats that not knowing the cause of the problem posed a safety concern for NASA. Hence the Anthropometry and Biomechanics Facility (ABF) of the Johnson Space Center was requested to perform an evaluation of the seat controls and provide NASA with appropriate recommendations on whether the seat lever positions and operations should be modified. The ABF designed an experiment to investigate the amount of pull force exerted by subjects, wearing an unpressurized or pressurized crew launch escape suit, when controls were placed in the front and back (on the right side) of the light-weight seat. Single-axis load cells were attached to the seat levers, which measured the maximum static pull forces that were exerted by the subjects. Twelve subjects, six male and six female, participated in this study. Each subject was asked to perform the pull test at least three times for each combination of lever position and suit pressure conditions. The results from this study showed that as a whole (or in general), the subjects were able to pull on the lever at the back position with only about half the amount of force that they were able to exert on the lever at the front position. In addition, the results also showed that subjects wearing the pressurized suit were unable to reach the seat lever when it was located at the back. Furthermore, the pull forces on the front lever diminished about 50 % when subjects wore the pressurized suits. Based on these results from this study, it was recommended to NASA that the levers should not be located in the back position. In addition, further investigation is needed on whether the levers at the front of the seat could be modified or adjusted to increase the leverage for crew members wearing pressurized launch/escape suits.
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Lui, Jordon; MacGillivray, Megan K; Sheel, A William; Jeyasurya, Jeswin; Sadeghi, Mahsa; Sawatzky, Bonita Jean
2013-01-01
The purpose of this study was to (1) evaluate the mechanical efficiency (ME) of two commercially available lever-propulsion mechanisms for wheelchairs and (2) compare the ME of lever propulsion with hand rim propulsion within the same wheelchair. Of the two mechanisms, one contained a torsion spring while the other used a roller clutch design. We hypothesized that the torsion spring mechanism would increase the ME of propulsion due to a passive recovery stroke enabled by the mechanism. Ten nondisabled male participants with no prior manual wheeling experience performed submaximal exercise tests using both lever-propulsion mechanisms and hand rim propulsion on two different wheelchairs. Cardiopulmonary parameters including oxygen uptake (VO2), heart rate (HR), and energy expenditure (En) were determined. Total external power (Pext) was measured using a drag test protocol. ME was determined by the ratio of Pext to En. Results indicated no significant effect of lever-propulsion mechanism for all physiological measures tested. This suggests that the torsion spring did not result in a physiological benefit compared with the roller clutch mechanism. However, both lever-propulsion mechanisms showed decreased VO2 and HR and increased ME (as a function of slope) compared with hand rim propulsion (p < 0.001). This indicates that both lever-propulsion mechanisms tested are more mechanically efficient than conventional hand rim propulsion, especially when slopes are encountered.
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The New Urban High School: A Practitioner's Guide.
ERIC Educational Resources Information Center
Big Picture Co., Cambridge, MA.
In October 1996, the Big Picture Company set out to find six urban high schools that use school-to-work strategies as a lever for whole-school reform. In the schools finally selected for the New Urban High Schools Project, and in others examined for the study, "school-to-work" is a misnomer, because the majority of students are entering…
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Fit for the Principalship: Identifying, Training, and Clearing the Path for Potential School Leaders
ERIC Educational Resources Information Center
Johnston, Mike; Walker, R. K.; Levine, Andy
2010-01-01
Since its inception, New Leaders for New Schools has been driven by the fundamental belief that every child can succeed academically at high levels. New Leaders for New Schools also believes that an effective principal is a crucial lever for school improvement and transforming student achievement at scale. Thus, a focus on the selection, training,…
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The precision and torque production of common hip adductor squeeze tests used in elite football.
Light, N; Thorborg, K
2016-11-01
Decreased hip adductor strength is a known risk factor for groin injury in footballers, with clinicians testing adductor strength in various positions and using different protocols. Understanding how reliable and how much torque different adductor squeeze tests produce will facilitate choosing the most appropriate method for future testing. In this study, the reliability and torque production of three common adductor squeeze tests were investigated. Test-retest reliability and cross-sectional comparison. Twenty elite level footballers (16-33 years) without previous or current groin pain were recruited. Relative and absolute test-retest reliability, and torque production of three adductor squeeze tests (long-lever in abduction, short-lever in adduction and short-lever in abduction/external rotation) were investigated. Each participant performed a series of isometric strength tests measured by hand-held dynamometry in each position, on two test days separated by two weeks. No systematic variation was seen for any of the tests when using the mean of three measures (ICC=0.84-0.97, MDC%=6.6-19.5). The smallest variation was observed when taking the mean of three repetitions in the long-lever position (ICC=0.97, MDC%=6.6). The long-lever test also yielded the highest mean torque values, which were 69% and 11% higher than the short-lever in adduction test and short-lever in abduction/external rotation test respectively (p<0.001). All three tests described in this study are reliable methods of measuring adductor squeeze strength. However, the test performed in the long-lever position seems the most promising as it displays high test-retest precision and the highest adductor torque production. Copyright © 2015 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.
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Noninvasive determination of optical lever sensitivity in atomic force microscopy
NASA Astrophysics Data System (ADS)
Higgins, M. J.; Proksch, R.; Sader, J. E.; Polcik, M.; Mc Endoo, S.; Cleveland, J. P.; Jarvis, S. P.
2006-01-01
Atomic force microscopes typically require knowledge of the cantilever spring constant and optical lever sensitivity in order to accurately determine the force from the cantilever deflection. In this study, we investigate a technique to calibrate the optical lever sensitivity of rectangular cantilevers that does not require contact to be made with a surface. This noncontact approach utilizes the method of Sader et al. [Rev. Sci. Instrum. 70, 3967 (1999)] to calibrate the spring constant of the cantilever in combination with the equipartition theorem [J. L. Hutter and J. Bechhoefer, Rev. Sci. Instrum. 64, 1868 (1993)] to determine the optical lever sensitivity. A comparison is presented between sensitivity values obtained from conventional static mode force curves and those derived using this noncontact approach for a range of different cantilevers in air and liquid. These measurements indicate that the method offers a quick, alternative approach for the calibration of the optical lever sensitivity.
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Cue-induced reinstatement of ethanol seeking in Sardinian alcohol-preferring rats.
Maccioni, Paola; Orrú, Alessandro; Korkosz, Agnieszka; Gessa, Gian Luigi; Carai, Mauro A M; Colombo, Giancarlo; Bienkowski, Przemyslaw
2007-02-01
The purpose of the present study was to characterize cue-induced reinstatement of ethanol seeking in selectively bred Sardinian alcohol-preferring (sP) rats trained to lever press for ethanol in 30-min self-administration sessions. Four responses on an "active" lever led to presentation of 0.1 ml of 15% (vol/vol) ethanol by a liquid dipper and concurrent activation of a set of discrete light and auditory cues. In a 70-min extinction/reinstatement session, responding was first extinguished for 60 min. Subsequently, different stimuli were delivered in a noncontingent manner and reinstatement of nonreinforced responding was assessed. Fifteen presentations of the ethanol-predictive stimulus complex, including the dipper cup containing 5 or 15% ethanol, potently reinstated responding on the previously active lever. The magnitude of reinstatement increased with the number of stimulus presentations and concentration of ethanol presented by the dipper cup. Fifteen presentations of the ethanol-predictive stimulus complex, including the dipper cup filled with water (0% ethanol), did not produce any reinstatement. These results indicate that (1) noncontingent presentations of the ethanol-predictive stimulus complex may reinstate ethanol seeking in sP rats and (2) the orosensory properties of ethanol may play an important role in reinstatement of ethanol seeking in sP rats. The latter finding concurs with clinical observations that odor and taste of alcoholic beverages elicit immediate craving responses in abstinent alcoholics.
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Error analysis and correction of lever-type stylus profilometer based on Nelder-Mead Simplex method
NASA Astrophysics Data System (ADS)
Hu, Chunbing; Chang, Suping; Li, Bo; Wang, Junwei; Zhang, Zhongyu
2017-10-01
Due to the high measurement accuracy and wide range of applications, lever-type stylus profilometry is commonly used in industrial research areas. However, the error caused by the lever structure has a great influence on the profile measurement, thus this paper analyzes the error of high-precision large-range lever-type stylus profilometry. The errors are corrected by the Nelder-Mead Simplex method, and the results are verified by the spherical surface calibration. It can be seen that this method can effectively reduce the measurement error and improve the accuracy of the stylus profilometry in large-scale measurement.
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Three-axis lever actuator with flexure hinges for an optical disk system
NASA Astrophysics Data System (ADS)
Han, Chang-Soo; Kim, Soo-Hyun
2002-10-01
A three-axis lever actuator with a flexure hinge has been designed and fabricated. This actuator is driven by electromagnetic force based on a coil-magnet system and can be used as a high precision actuator and, especially as a pickup head actuator in optical disks. High precision and low sensitivity to external vibration are the major advantages of this lever actuator. An analysis model was found and compared to the finite element method. Dynamic characteristics of the three-axis lever actuator were measured. The results are in very close agreement to those predicted by the model and finite element analysis.
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Hard turning micro-machine tool
DeVor, Richard E; Adair, Kurt; Kapoor, Shiv G
2013-10-22
A micro-scale apparatus for supporting a tool for hard turning comprises a base, a pivot coupled to the base, an actuator coupled to the base, and at least one member coupled to the actuator at one end and rotatably coupled to the pivot at another end. A tool mount is disposed on the at least one member. The at least one member defines a first lever arm between the pivot and the tool mount, and a second lever arm between the pivot and the actuator. The first lever arm has a length that is less than a length of the second lever arm. The actuator moves the tool mount along an arc.
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Gao, Yang; Li, Hongsheng; Huang, Libin; Sun, Hui
2017-04-30
This paper presents the design and application of a lever coupling mechanism to improve the shock resistance of a dual-mass silicon micro-gyroscope with drive mode coupled along the driving direction without sacrificing the mechanical sensitivity. Firstly, the mechanical sensitivity and the shock response of the micro-gyroscope are theoretically analyzed. In the mechanical design, a novel lever coupling mechanism is proposed to change the modal order and to improve the frequency separation. The micro-gyroscope with the lever coupling mechanism optimizes the drive mode order, increasing the in-phase mode frequency to be much larger than the anti-phase one. Shock analysis results show that the micro-gyroscope structure with the designed lever coupling mechanism can notably reduce the magnitudes of the shock response and cut down the stress produced in the shock process compared with the traditional elastic coupled one. Simulations reveal that the shock resistance along the drive direction is greatly increased. Consequently, the lever coupling mechanism can change the gyroscope's modal order and improve the frequency separation by structurally offering a higher stiffness difference ratio. The shock resistance along the driving direction is tremendously enhanced without loss of the mechanical sensitivity.
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Weatherly, Jeffrey N; Arthur, Emily I L; Nurnberger, Jeri T
2006-01-01
Researchers have demonstrated that rats reliably increase their rates of pressing a lever for 1% liquid-sucrose reinforcement if they will soon have the opportunity to press a lever for food-pellet reinforcement. In the present experiments, the authors investigated if this increase in response rates occurred because the upcoming food pellets produced an increase in all behaviors (i.e., general arousal) or an increase in only the specific operant response (i.e., lever pressing). The results of Experiments 1 and 2 showed that the appearance of induction in rats' lever pressing for 1% sucrose reinforcement when food-pellet reinforcement was upcoming did not coincide with increases in the frequency of running in a wheel or making a nonreinforced nose-poke response. On the other hand, in Experiment 3, the authors found the appearance of induction coincided with increase nonreinforced lever presses on an adjacent lever. These results shed doubt on the idea that induction is a result of a general increase in all activity, and suggest instead that the increase in responding that occurs during induction is limited to the operant response.
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Adding Stiffness to the Foot Modulates Soleus Force-Velocity Behaviour during Human Walking
Takahashi, Kota Z.; Gross, Michael T.; van Werkhoven, Herman; Piazza, Stephen J.; Sawicki, Gregory S.
2016-01-01
Previous studies of human locomotion indicate that foot and ankle structures can interact in complex ways. The structure of the foot defines the input and output lever arms that influences the force-generating capacity of the ankle plantar flexors during push-off. At the same time, deformation of the foot may dissipate some of the mechanical energy generated by the plantar flexors during push-off. We investigated this foot-ankle interplay during walking by adding stiffness to the foot through shoes and insoles, and characterized the resulting changes in in vivo soleus muscle-tendon mechanics using ultrasonography. Added stiffness decreased energy dissipation at the foot (p < 0.001) and increased the gear ratio (i.e., ratio of ground reaction force and plantar flexor muscle lever arms) (p < 0.001). Added foot stiffness also altered soleus muscle behaviour, leading to greater peak force (p < 0.001) and reduced fascicle shortening speed (p < 0.001). Despite this shift in force-velocity behaviour, the whole-body metabolic cost during walking increased with added foot stiffness (p < 0.001). This increased metabolic cost is likely due to the added force demand on the plantar flexors, as walking on a more rigid foot/shoe surface compromises the plantar flexors’ mechanical advantage. PMID:27417976
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Adding Stiffness to the Foot Modulates Soleus Force-Velocity Behaviour during Human Walking
NASA Astrophysics Data System (ADS)
Takahashi, Kota Z.; Gross, Michael T.; van Werkhoven, Herman; Piazza, Stephen J.; Sawicki, Gregory S.
2016-07-01
Previous studies of human locomotion indicate that foot and ankle structures can interact in complex ways. The structure of the foot defines the input and output lever arms that influences the force-generating capacity of the ankle plantar flexors during push-off. At the same time, deformation of the foot may dissipate some of the mechanical energy generated by the plantar flexors during push-off. We investigated this foot-ankle interplay during walking by adding stiffness to the foot through shoes and insoles, and characterized the resulting changes in in vivo soleus muscle-tendon mechanics using ultrasonography. Added stiffness decreased energy dissipation at the foot (p < 0.001) and increased the gear ratio (i.e., ratio of ground reaction force and plantar flexor muscle lever arms) (p < 0.001). Added foot stiffness also altered soleus muscle behaviour, leading to greater peak force (p < 0.001) and reduced fascicle shortening speed (p < 0.001). Despite this shift in force-velocity behaviour, the whole-body metabolic cost during walking increased with added foot stiffness (p < 0.001). This increased metabolic cost is likely due to the added force demand on the plantar flexors, as walking on a more rigid foot/shoe surface compromises the plantar flexors’ mechanical advantage.
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Adding Stiffness to the Foot Modulates Soleus Force-Velocity Behaviour during Human Walking.
Takahashi, Kota Z; Gross, Michael T; van Werkhoven, Herman; Piazza, Stephen J; Sawicki, Gregory S
2016-07-15
Previous studies of human locomotion indicate that foot and ankle structures can interact in complex ways. The structure of the foot defines the input and output lever arms that influences the force-generating capacity of the ankle plantar flexors during push-off. At the same time, deformation of the foot may dissipate some of the mechanical energy generated by the plantar flexors during push-off. We investigated this foot-ankle interplay during walking by adding stiffness to the foot through shoes and insoles, and characterized the resulting changes in in vivo soleus muscle-tendon mechanics using ultrasonography. Added stiffness decreased energy dissipation at the foot (p < 0.001) and increased the gear ratio (i.e., ratio of ground reaction force and plantar flexor muscle lever arms) (p < 0.001). Added foot stiffness also altered soleus muscle behaviour, leading to greater peak force (p < 0.001) and reduced fascicle shortening speed (p < 0.001). Despite this shift in force-velocity behaviour, the whole-body metabolic cost during walking increased with added foot stiffness (p < 0.001). This increased metabolic cost is likely due to the added force demand on the plantar flexors, as walking on a more rigid foot/shoe surface compromises the plantar flexors' mechanical advantage.
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Levers for Change in Educational Development in Canada: Looking Back, Looking Forward
ERIC Educational Resources Information Center
Dawson, Debra L.
2017-01-01
This paper examines levers or drivers that have influenced the direction of educational development in Canada over the last 40 years and also tries to predict what will be the impact of some current levers on changing the work of developers in the next 20 years. Reflecting on those years, it is apparent our work in the 1980s was very focused on…
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A Lever for Life: How I Lost 150 Pounds and Learned the Catalytic Power of School Community
ERIC Educational Resources Information Center
Ebner, Steven J.
2011-01-01
The quotation, attributed to the Greek mathematician Archimedes, about the power of levers to move the world has been quoted many times with slight variations, but usually the point is the same: "With the right lever, one can move the earth." However, the actual quotation attributed to Archimedes comes in the writings of another Greek…
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Harvey, Roxann C; Jordan, Chloe J; Tassin, David H; Moody, Kayla R; Dwoskin, Linda P; Kantak, Kathleen M
2013-01-01
Research examining medication effects on set shifting in teens with attention deficit/hyperactivity disorder (ADHD) is lacking. An animal model of ADHD may be useful for exploring this gap. The Spontaneously Hypertensive Rat (SHR) is a commonly used animal model of ADHD. SHR and two comparator strains, Wistar-Kyoto (WKY) and Wistar (WIS), were evaluated during adolescence in a strategy set shifting task under conditions of a 0-sec or 15-sec delay to reinforcer delivery. The task had three phases: initial discrimination, set shift and reversal learning. Under 0-sec delays, SHR performed as well as or better than WKY and WIS. Treatment with 0.3 mg/kg/day atomoxetine had little effect, other than to modestly increase trials to criterion during set shifting in all strains. Under 15-sec delays, SHR had longer lever press reaction times, longer latencies to criterion and more trial omissions than WKY during set shifting and reversal learning. These deficits were not reduced systematically by 1.5 mg/kg/day methylphenidate or 0.3 mg/kg/day atomoxetine. Regarding learning in SHR, methylphenidate improved initial discrimination, whereas atomoxetine improved set shifting but disrupted initial discrimination. During reversal learning, both drugs were ineffective in SHR, and atomoxetine made reaction time and trial omissions greater in WKY. Overall, WIS performance differed from SHR or WKY, depending on phase. Collectively, a genetic model of ADHD in adolescent rats revealed that neither methylphenidate nor atomoxetine mitigated all deficits in SHR during the set shifting task. Thus, methylphenidate or atomoxetine monotherapy may not mitigate all set shift task-related deficits in teens with ADHD. PMID:23376704
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Topical Meeting of Broadband Analog and Digital Optoelectronics
1992-01-01
effects [2]. Laser nonlinearitics can be minimised by careful design of the device to maximise the relaxation oscillation resonance frequency [2...feedback loop ultimately limits the stability of the circuit and determines the maximum frequency of operation. With hybrid circuit constructioi. this...range and number of accessible frequency channels), the tuning lever, and the filter selectivity (which determines the side-mode suppression ratio (SMSR
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Salling, Michael C.; Hodge, Christopher J.; Psilos, Kelly E.; Eastman, Vallari R.; Faccidomo, Sara P.; Hodge, Clyde W.
2018-01-01
Cue-induced reinstatement of alcohol-seeking is a hallmark behavioral pathology of addiction. Evidence suggests that reinstatement (e.g., relapse), may be regulated by cell signaling systems that underlie neuroplasticity. A variety of plasticity events require activation of calcium calmodulin-dependent protein kinase II (CaMKII) in components of the reward pathway, such as the nucleus accumbens and amygdala. We sought to determine if cue-induced reinstatement of alcohol-seeking behavior is associated with changes in the activation state (e.g., phosphorylation) of CaMKII-T286. Male C57BL/6J mice (n = 14) were trained to lever press on a fixed-ratio-4 schedule of sweetened alcohol (2% sucrose + 9% EtOH) reinforcement. After 14-d of extinction (no cues or reinforcers), mice underwent a response-contingent reinstatement (n = 7) vs. an additional day of extinction (n = 7). Brains were removed immediately after the test and processed for evaluation of pCaMKII-T286 immunoreactivity (IR). Number of pCaMKII-T286 positive cells/mm2 was quantified from coronal brain sections using Bioquant Image Analysis software. Mice emitted significantly more responses on the alcohol vs. the inactive lever throughout the baseline phase with average alcohol intake of 1.1 ± 0.03 g/kg/1-h. During extinction, responses on the alcohol lever decreased to inactive lever levels by day 7. Significant cue-induced reinstatement of alcohol-seeking was observed during a single test with no effects on the inactive lever. Reinstatement was associated with increased pCaMKII-T286 IR specifically in amygdala (LA and BLA), nucleus accumbens (AcbSh), lateral septum, mediodorsal thalamus, and piriform cortex as compared to extinction control. Brain regions showing no change included the dorsal striatum, medial septum, cingulate cortex, habenula, paraventricular thalamus, and ventral hypothalamus. These results show response contingent cue-induced reinstatement of alcohol-seeking behavior is associated with selective increases in pCaMKII-T286 in specific reward- and memory-related brain regions of male C57BL/6J mice. Primary molecular mechanisms of associative learning and memory may regulate relapse in alcohol addiction. PMID:29100991
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Kock, L.J.
1959-09-22
A device is presented for loading and unloading fuel elements containing material fissionable by neutrons of thermal energy. The device comprises a combination of mechanical features Including a base, a lever pivotally attached to the base, an Indexing plate on the base parallel to the plane of lever rotation and having a plurality of apertures, the apertures being disposed In rows, each aperture having a keyway, an Index pin movably disposed to the plane of lever rotation and having a plurality of apertures, the apertures being disposed in rows, each aperture having a keyway, an index pin movably disposed on the lever normal to the plane rotation, a key on the pin, a sleeve on the lever spaced from and parallel to the index pin, a pair of pulleys and a cable disposed between them, an open collar rotatably attached to the sleeve and linked to one of the pulleys, a pin extending from the collar, and a bearing movably mounted in the sleeve and having at least two longitudinal grooves in the outside surface.
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Zhao, Xiaoyan; Qin, Renjia
2015-04-01
This paper makes persuasive demonstrations on some problems about the human ear sound transmission principle in existing physiological textbooks and reference books, and puts forward the authors' view to make up for its literature. Exerting the knowledge of lever in physics and the acoustics theory, we come up with an equivalent simplified model of manubrium mallei which is to meet the requirements as the long arm of the lever. We also set up an equivalent simplified model of ossicular chain--a combination of levers of ossicular chain. We disassemble the model into two simple levers, and make full analysis and demonstration on them. Through the calculation and comparison of displacement amplitudes in both external auditory canal air and internal ear lymph, we may draw a conclusion that the key reason, which the sound displacement amplitude is to be decreased to adapt to the endurance limit of the basement membrane, is that the density and sound speed in lymph is much higher than those in the air.
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Pin-Retraction Mechanism On Quick-Release Cover
NASA Technical Reports Server (NTRS)
Macmartin, Malcolm
1994-01-01
Quick-release cover includes pin-retraction mechanism releasing cover quickly from lower of two sets of pin connections holding cover. Cover released at top by pulling lever as described in "Lever-Arm Pin Puller" (NPO-18788). Removal of cover begins when technician or robot pulls upper-pin-release lever. Cover swings downward until tabs on lower pins are pulled through slots in their receptacles. Lower pins are then free.
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Speed-Selector Guard For Machine Tool
NASA Technical Reports Server (NTRS)
Shakhshir, Roda J.; Valentine, Richard L.
1992-01-01
Simple guardplate prevents accidental reversal of direction of rotation or sudden change of speed of lathe, milling machine, or other machine tool. Custom-made for specific machine and control settings. Allows control lever to be placed at only one setting. Operator uses handle to slide guard to engage or disengage control lever. Protects personnel from injury and equipment from damage occurring if speed- or direction-control lever inadvertently placed in wrong position.
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Flexural Stiffness of Myosin Va Subdomains as Measured from Tethered Particle Motion
Michalek, Arthur J.; Kennedy, Guy G.; Warshaw, David M.; Ali, M. Yusuf
2015-01-01
Myosin Va (MyoVa) is a processive molecular motor involved in intracellular cargo transport on the actin cytoskeleton. The motor's processivity and ability to navigate actin intersections are believed to be governed by the stiffness of various parts of the motor's structure. Specifically, changes in calcium may regulate motor processivity by altering the motor's lever arm stiffness and thus its interhead communication. In order to measure the flexural stiffness of MyoVa subdomains, we use tethered particle microscopy, which relates the Brownian motion of fluorescent quantum dots, which are attached to various single- and double-headed MyoVa constructs bound to actin in rigor, to the motor's flexural stiffness. Based on these measurements, the MyoVa lever arm and coiled-coil rod domain have comparable flexural stiffness (0.034 pN/nm). Upon addition of calcium, the lever arm stiffness is reduced 40% as a result of calmodulins potentially dissociating from the lever arm. In addition, the flexural stiffness of the full-length MyoVa construct is an order of magnitude less stiff than both a single lever arm and the coiled-coil rod. This suggests that the MyoVa lever arm-rod junction provides a flexible hinge that would allow the motor to maneuver cargo through the complex intracellular actin network. PMID:26770194
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Gao, Yang; Li, Hongsheng; Huang, Libin; Sun, Hui
2017-01-01
This paper presents the design and application of a lever coupling mechanism to improve the shock resistance of a dual-mass silicon micro-gyroscope with drive mode coupled along the driving direction without sacrificing the mechanical sensitivity. Firstly, the mechanical sensitivity and the shock response of the micro-gyroscope are theoretically analyzed. In the mechanical design, a novel lever coupling mechanism is proposed to change the modal order and to improve the frequency separation. The micro-gyroscope with the lever coupling mechanism optimizes the drive mode order, increasing the in-phase mode frequency to be much larger than the anti-phase one. Shock analysis results show that the micro-gyroscope structure with the designed lever coupling mechanism can notably reduce the magnitudes of the shock response and cut down the stress produced in the shock process compared with the traditional elastic coupled one. Simulations reveal that the shock resistance along the drive direction is greatly increased. Consequently, the lever coupling mechanism can change the gyroscope’s modal order and improve the frequency separation by structurally offering a higher stiffness difference ratio. The shock resistance along the driving direction is tremendously enhanced without loss of the mechanical sensitivity. PMID:28468288
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Frenk, Hanan; Martin, Jeffrey; Vitouchanskaia, Cristina; Dar, Reuven; Shalev, Uri
2017-01-05
Nicotine has been proposed to be a primary reinforcer and a reinforcement enhancer. To date, no studies have examined whether nicotine enhances consummatory behaviors or only operant responding (appetitive behaviors). Experiments were designed to test whether contingent and noncontingent nicotine enhance lever pressing for and consumption of fluids in water-deprived rats. Animals were water-deprived throughout all experiments. They were trained to press two levers under a variable interval (VI-20, 1-35s). Their lever pressing and water consumption were measured after noncontingent subcutaneous (s.c.) injection of nicotine (1mg/kg), and in 3 choice conditions (water and quinine solution (18µg/ml); water and nicotine (32µg/ml) solution; quinine (18µg/ml) and nicotine (32µg/ml) solutions) where nicotine was thus delivered contingently upon lever pressing. The effects of nicotine (1mg/kg; s.c.) on the consumption of water in a time-limited free access (1h) paradigm were assessed. Nicotine significantly increased lever pressing and the number of earned reinforcements on both levers in the two choice conditions and when administered s.c. compared to all groups that did not receive nicotine. However, under no condition did animals consume more fluids than baseline. Under the time-limited free access condition nicotine reduced water consumption. Although our findings do not support a reinforcing effect for nicotine, they are consistent with the incentive-amplification hypothesis. Its relevance for human smoking is yet unclear. Copyright © 2016 Elsevier B.V. All rights reserved.
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Buffalari, Deanne M; Feltenstein, Matthew W; See, Ronald E
2013-11-01
Cue exposure therapy, which attempts to limit relapse by reducing reactivity to cocaine-paired cues through repeated exposures, has had limited success. The current experiments examined cocaine cue-induced anxiogenesis and investigated whether a model of cue exposure therapy would reduce reinstatement of cocaine seeking in rats with a history of cocaine self-administration. Male rats experienced daily intravenous cocaine self-administration. Rats then experienced exposure to either the self-administration context or the context plus noncontingent presentations of cocaine-paired cues. Immediately following exposure, anxiety-like behavior was measured using elevated plus maze and defensive burying tests. In a second group of rats, self-administration was followed by 7 days of exposure to the context, context + noncontingent cue exposure, lever extinction, or cue + lever extinction. All animals then underwent two contingent cue-induced reinstatement tests separated by 7 days of lever extinction. Exposure to noncontingent cocaine-paired cues in the self-administration context increased anxiety-like behavior on the defensive burying test. Animals that experienced lever + cue extinction displayed the least cocaine seeking on the first reinstatement test, and lever extinction reduced cocaine seeking below context exposure or context + noncontingent cue exposure. All animals had similar levels of cocaine seeking on the second reinstatement test. Noncontingent cue exposure causes anxiety, and noncontingent cue and context exposure are less effective at reducing contingent cue-induced reinstatement than lever or lever + cue extinction. These data indicate that active extinction of the drug-taking response may be critical for reduction of relapse proclivity in former cocaine users.
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The Role of the Lateral Habenula in Punishment
Jean-Richard Dit Bressel, Philip; McNally, Gavan P.
2014-01-01
The lateral habenula (LHb) is a small epithalamic structure that projects via the fasciculus retroflexus to the midbrain. The LHb is known to modulate midbrain dopamine (DA) neurons, including inhibition of ventral tegmental area (VTA) neurons via glutamatergic excitation of the GABAergic rostromedial tegmental nucleus (RMTg). A variety of lines of evidence show activity in LHb and the LHb-RMTg pathway is correlated with, and is sufficient to support, punishment learning. However, it is not immediately clear whether LHb is necessary for punishment. Here we used a within-subjects punishment task to assess the role of LHb in the acquisition and expression of punishment as well as in aversive choice. Rats that pressed two individually presented levers for pellet rewards rapidly suppressed responding to one lever if it also caused footshock deliveries (punished lever) but continued pressing a second lever that did not cause footshock (unpunished lever). Infusions of an AMPA receptor antagonist (NBQX) into LHb had no effect on the acquisition or expression of this punishment, or on aversive choice, but did increase locomotion. Infusion of the sodium channel blocker bupivacaine likewise had no effect on expression of punishment. However, infusion of the calcium channel blocker mibefradil did affect expression of punishment by significantly decreasing the latency with which rats responded on the punished lever and significantly increasing unpunished lever-pressing. Taken together, these findings indicate that the LHb plays a limited role in punishment, influencing only latency to respond. This role is linked to calcium channel permeability and not AMPA receptor or sodium channel permeability. PMID:25365401
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The role of the basolateral amygdala in punishment
Jean-Richard-Dit-Bressel, Philip
2015-01-01
Aversive stimuli not only support fear conditioning to their environmental antecedents, they also punish behaviors that cause their occurrence. The amygdala, especially the basolateral nucleus (BLA), has been critically implicated in Pavlovian fear learning but its role in punishment remains poorly understood. Here, we used a within-subjects punishment task to assess the role of the BLA in the acquisition and expression of punishment as well as aversive choice. Rats that pressed two individually presented levers for pellet rewards rapidly suppressed responding to one lever if it also caused footshock deliveries (punished lever) but continued pressing a second lever that did not cause footshock (unpunished lever). Infusions of GABA agonists baclofen and muscimol (BM) into the BLA significantly impaired the acquisition of this suppression. BLA inactivations using BM also reduced the expression of well-trained punishment. There was anatomical segregation within the BLA so that caudal, not rostral, BLA was implicated in punishment. However, when presented with punished and unpunished levers simultaneously in a choice test without deliveries of shock punisher, rats expressed a preference for unpunished over the punished lever and BLA inactivations had no effect on this preference. Taken together, these findings indicate that the BLA is important for both the acquisition and expression of punishment but not for aversive choice. This role appears to be linked to neurons in the caudal BLA, rather than rostral BLA, although the circuitry that contributes to this functional segregation is currently unknown, and is most parsimoniously interpreted as a role for caudal BLA in determining the aversive value of the shock punisher. PMID:25593299
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The role of the lateral habenula in punishment.
Jean-Richard Dit Bressel, Philip; McNally, Gavan P
2014-01-01
The lateral habenula (LHb) is a small epithalamic structure that projects via the fasciculus retroflexus to the midbrain. The LHb is known to modulate midbrain dopamine (DA) neurons, including inhibition of ventral tegmental area (VTA) neurons via glutamatergic excitation of the GABAergic rostromedial tegmental nucleus (RMTg). A variety of lines of evidence show activity in LHb and the LHb-RMTg pathway is correlated with, and is sufficient to support, punishment learning. However, it is not immediately clear whether LHb is necessary for punishment. Here we used a within-subjects punishment task to assess the role of LHb in the acquisition and expression of punishment as well as in aversive choice. Rats that pressed two individually presented levers for pellet rewards rapidly suppressed responding to one lever if it also caused footshock deliveries (punished lever) but continued pressing a second lever that did not cause footshock (unpunished lever). Infusions of an AMPA receptor antagonist (NBQX) into LHb had no effect on the acquisition or expression of this punishment, or on aversive choice, but did increase locomotion. Infusion of the sodium channel blocker bupivacaine likewise had no effect on expression of punishment. However, infusion of the calcium channel blocker mibefradil did affect expression of punishment by significantly decreasing the latency with which rats responded on the punished lever and significantly increasing unpunished lever-pressing. Taken together, these findings indicate that the LHb plays a limited role in punishment, influencing only latency to respond. This role is linked to calcium channel permeability and not AMPA receptor or sodium channel permeability.
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Stirling engine power control and motion conversion mechanism
Marks, David T.
1983-01-01
A motion conversion device for converting between the reciprocating motion of the pistons in a Stirling engine and the rotating motion of its output shaft, and for changing the stroke and phase of the pistons, includes a lever pivoted at one end and having a cam follower at the other end. The piston rod engages the lever intermediate its ends and the cam follower engages a cam keyed to the output shaft. The lever pivot can be moved to change the length of the moment arm defined between the cam follower and the piston rod the change the piston stroke and force exerted on the cam, and the levers can be moved in opposite directions to change the phase between pistons.
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Examining the role of dopamine D2 and D3 receptors in Pavlovian conditioned approach behaviors.
Fraser, Kurt M; Haight, Joshua L; Gardner, Eliot L; Flagel, Shelly B
2016-05-15
Elucidating the neurobiological mechanisms underlying individual differences in the extent to which reward cues acquire the ability to act as incentive stimuli may contribute to the development of successful treatments for addiction and related disorders. We used the sign-tracker/goal-tracker animal model to examine the role of dopamine D2 and D3 receptors in the propensity to attribute incentive salience to reward cues. Following Pavlovian training, wherein a discrete lever-cue was paired with food reward, rats were classified as sign- or goal-trackers based on the resultant conditioned response. We examined the effects of D2/D3 agonists, 7-OH-DPAT (0.01-0.32mg/kg) or pramipexole (0.032-0.32mg/kg), the D2/D3 antagonist raclopride (0.1mg/kg), and the selective D3 antagonist, SB-277011A (6 or 24mg/kg), on the expression of sign- and goal-tracking conditioned responses. The lever-cue acquired predictive value and elicited a conditioned response for sign- and goal-trackers, but only for sign-trackers did it also acquire incentive value. Following administration of either 7-OH-DPAT, pramipexole, or raclopride, the performance of the previously acquired conditioned response was attenuated for both sign- and goal-trackers. For sign-trackers, the D2/D3 agonist, 7-OH-DPAT, also attenuated the conditioned reinforcing properties of the lever-cue. The selective D3 antagonist did not affect either conditioned response. Alterations in D2/D3 receptor signaling, but not D3 signaling alone, transiently attenuate a previously acquired Pavlovian conditioned response, regardless of whether the response is a result of incentive motivational processes. These findings suggest activity at the dopamine D2 receptor is critical for a reward cue to maintain either its incentive or predictive qualities. Copyright © 2016 Elsevier B.V. All rights reserved.
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Examining the Role of Dopamine D2 and D3 Receptors in Pavlovian Conditioned Approach Behaviors
Fraser, Kurt M.; Haight, Joshua L.; Gardner, Eliot L.; Flagel, Shelly B.
2016-01-01
Elucidating the neurobiological mechanisms underlying individual differences in the extent to which reward cues acquire the ability to act as incentive stimuli may contribute to the development of successful treatments for addiction and related disorders. We used the sign-tracker/goal-tracker animal model to examine the role of dopamine D2 and D3 receptors in the propensity to attribute incentive salience to reward cues. Following Pavlovian training, wherein a discrete lever-cue was paired with food reward, rats were classified as sign- or goal-trackers based on the resultant conditioned response. We examined the effects of D2/D3 agonists, 7-OH-DPAT (0.01–0.32 mg/kg) or pramipexole (0.032–0.32 mg/kg), the D2/D3 antagonist raclopride (0.1 mg/kg), and the selective D3 antagonist, SB-277011A (6 or 24 mg/kg), on the expression of sign- and goal-tracking conditioned responses. The lever-cue acquired predictive value and elicited a conditioned response for sign- and goal-trackers, but only for sign-trackers did it also acquire incentive value. Following administration of either 7-OH-DPAT, pramipexole, or raclopride, the performance of the previously acquired conditioned response was attenuated for both sign- and goal-trackers. For sign-trackers, the D2/D3 agonist, 7-OH-DPAT, also attenuated the conditioned reinforcing properties of the lever-cue. The selective D3 antagonist did not affect either conditioned response. Alterations in D2/D3 receptor signaling, but not D3 signaling alone, transiently attenuate a previously acquired Pavlovian conditioned response, regardless of whether the response is a result of incentive motivational processes. These findings suggest activity at the dopamine D2 receptor is critical for a reward cue to maintain either its incentive or predictive qualities. PMID:26909847
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Hafenbreidel, Madalyn; Rafa Todd, Carolynn; Mueller, Devin
2017-01-01
Addiction is characterized by high relapse susceptibility, and relapse can be triggered by drug-associated cues. Cue presentation induces retrieval of the drug-cue memory, which becomes labile and must be reconsolidated into long-term storage. Repeated unpaired cue presentation, however, promotes extinction. Cue-reactivity can be reduced by blocking reconsolidation or facilitating extinction, which are mediated by NMDA receptors (NMDArs). However, the role of NMDArs in either process following self-administration is unclear. Thus, to determine their role in extinction, rats learned to self-administer cocaine before receiving injections of the NMDAr antagonist CPP immediately after four 45-min extinction sessions. During a subsequent 90-min extinction retention test, CPP-treated rats lever pressed less than saline-treated rats indicating that NMDAr blockade facilitated extinction or disrupted drug-cue memory reconsolidation. In addition, infusing CPP into the infralimbic medial prefrontal cortex (IL-mPFC), a structure implicated in extinction, before four 45-min or immediately after four 30min extinction sessions, had similar results during the extinction retention tests. Next, the GluN2A-selective antagonist NVP or GluN2B-selective antagonist Ro25 was infused into IL-mPFC or nucleus accumbens (NAc) shell, another structure implicated in extinction, after four 45-min extinction sessions. Blocking GluN2A-, but not GluN2B-, containing NMDArs, in IL-mPFC or NAc shell reduced lever pressing during the extinction retention tests. Finally, to dissociate reconsolidation from extinction, NVP was infused into IL-mPFC after four 10-min reactivation sessions, which resulted in reduced lever pressing during the retention test. These results indicate that IL-mPFC GluN2A-containing NMDArs modulate reconsolidation, and suggest a novel treatment strategy, as reducing cue reactivity could limit relapse susceptibility. PMID:28042872
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Hospital profitability and capital structure: a comparative analysis.
Valvona, J; Sloan, F A
1988-01-01
This article compares the financial performance of hospitals by ownership type and of five publicly traded hospital companies with other industries, using such indicators as profit margins, return on equity (ROE) and total capitalization, and debt-to-equity ratios. We also examine stock returns to investors for the five hospital companies versus other industries, as well as the relative roles of debt and equity in new financing. Investor-owned hospitals had substantially greater margins and ROE than did other hospital types. In 1982, investor-owned chain hospitals had a ROE of 26 percent, 18 points above the average for all hospitals. Stock returns on the five selected hospital companies were more than twice as large as returns on other industries between 1972 and 1983. However, after 1983, returns for these companies fell dramatically in absolute terms and relative to other industries. We also found investor-owned hospitals to be much more highly levered than their government and voluntary counterparts, and more highly levered than other industries as well. PMID:3403274
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Kutz, Dieter F; Schmid, Barbara C; Meindl, Tobias; Timmann, Dagmar; Kolb, Florian P
2016-08-01
The "raspberry task" represents a precision grip task that requires continuous adjustment of grip forces and pull forces. During this task, subjects use a specialised grip rod and have to increase the pull force linearly while the rod is locked. The positions of the fingers are unrestrained and freely selectable. From the finger positions and the geometry of the grip rod, a physical lever was derived which is a comprehensive measurement of the subject's grip behaviour. In this study, the involvement of the cerebellum in establishing cued force changes (CFC) was examined. The auditory stimulus was associated with a motor behaviour that has to be readjusted during an ongoing movement that already started. Moreover, cerebellar involvement on grip behaviour was examined. The results show that patients presenting with degenerating cerebellar disease (CBL) were able to elicit CFC and were additionally able to optimise grip behaviour by minimising the lever. Comparison of the results of CBL with a control group of healthy subjects showed, however, that the CFC incidence was significantly lower and the reduction of the lever was less in CBL. Hence, the cerebellum is involved not only in the classical conditioning of reflexes but also in the association of sensory stimuli with complex changes in motor behaviour. Furthermore, the cerebellum is involved in the optimisation of grip behaviour during ongoing movements. Recent studies lead to the assumption that the cerebello-reticulo-spinal pathway might be important for the reduced optimisation of grip behaviour in CBL.
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The role of the basolateral amygdala in punishment.
Jean-Richard-Dit-Bressel, Philip; McNally, Gavan P
2015-02-01
Aversive stimuli not only support fear conditioning to their environmental antecedents, they also punish behaviors that cause their occurrence. The amygdala, especially the basolateral nucleus (BLA), has been critically implicated in Pavlovian fear learning but its role in punishment remains poorly understood. Here, we used a within-subjects punishment task to assess the role of the BLA in the acquisition and expression of punishment as well as aversive choice. Rats that pressed two individually presented levers for pellet rewards rapidly suppressed responding to one lever if it also caused footshock deliveries (punished lever) but continued pressing a second lever that did not cause footshock (unpunished lever). Infusions of GABA agonists baclofen and muscimol (BM) into the BLA significantly impaired the acquisition of this suppression. BLA inactivations using BM also reduced the expression of well-trained punishment. There was anatomical segregation within the BLA so that caudal, not rostral, BLA was implicated in punishment. However, when presented with punished and unpunished levers simultaneously in a choice test without deliveries of shock punisher, rats expressed a preference for unpunished over the punished lever and BLA inactivations had no effect on this preference. Taken together, these findings indicate that the BLA is important for both the acquisition and expression of punishment but not for aversive choice. This role appears to be linked to neurons in the caudal BLA, rather than rostral BLA, although the circuitry that contributes to this functional segregation is currently unknown, and is most parsimoniously interpreted as a role for caudal BLA in determining the aversive value of the shock punisher. © 2015 Jean-Richard-Dit-Bressel and McNally; Published by Cold Spring Harbor Laboratory Press.
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A conflict rat model of cue-induced relapse to cocaine seeking.
Cooper, Ayelet; Barnea-Ygael, Noam; Levy, Dino; Shaham, Yavin; Zangen, Abraham
2007-09-01
Relapse to drug use in humans can be induced by exposure to drug-associated cues. The ability of drug cues to provoke 'relapse' has been studied in laboratory animals using a reinstatement model in which resumption of drug seeking is assessed after extinction of drug-reinforced responding. In this model, there are no adverse consequences of drug-seeking behavior. However, in humans, abstinence is often self-imposed, and relapse episodes likely involve making a choice between the desire for the drug and the negative consequences of pursuing it (a conflict situation). In this paper, we describe a conflict model of cue-induced relapse in rats that approximate the human condition. Rats were trained to lever press for cocaine; infusions were paired with a discrete light cue. An 'electric barrier' was then introduced by electrifying the floor area near the levers. Responding decreased over days with increasing shock intensities, until the rats did not approach the levers for 3 days. Subsequently, the effect of intermittent noncontingent light-cue presentations on resumption of lever responding (relapse) was assessed in extinction tests, with the electric barrier remaining activated; during testing, lever presses led to contingent light-cue presentations. Noncontingent cue exposure led to resumption of lever presses during the relapse tests in 14 of the 24 rats. Surprisingly, 24 h later, 11 of the 24 rats resumed lever responding in a subsequent post-noncontingent cue test under similar extinction conditions. Large individual differences in responding were observed during both tests. At its current stage of development, the conflict relapse model appears particularly suitable for studying individual differences in cue-induced relapse to cocaine seeking or factors that promote this relapse.
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Kearns, David N; Weiss, Stanley J
2007-07-01
In pigeons, Pavlovian autoshaped keypecking produced by keylight-food pairings has been eliminated by introducing food during periods between CS presentations (i.e., during the inter-trial intervals). Keypecking eliminated in this manner reappears when the inter-trial USs are discontinued even though the CS is no longer paired with US. The present experiment investigated whether this recovery of responding produced by discontinuing unpaired inter-trial US presentations could be extended to another species, rats, within a Pavlovian sign-tracking paradigm. Rats were initially trained on a procedure where insertion of one retractable lever (CS(+)) was followed, response independently, with food, while insertion of another lever (CS(-)) was not paired with food. Rats quickly came to contact the CS(+) lever at high rates, but contacted the CS(-) lever infrequently. In the next phase, CS(+) was no longer followed by food. Explicitly unpaired food was presented only during the inter-trial intervals when both levers were absent. This treatment essentially eliminated the sign-tracking response. In the final phase, the unpaired inter-trial food presentations were discontinued while both CSs continued to be presented without food. This produced a significant recovery of the sign-tracking elicited by the CS(+) lever, extending the species generality of the Pavlovian resurgence phenomenon that has previously only been reported in pigeons, to rats.
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Fischer, William H.; Yoon, Kue H.
1984-04-10
A gas-insulated transmission line includes a corrugated outer conductor, an inner conductor disposed within and insulated from the outer conductor by means of support insulators and an insulating gas, and a transport device for supporting and permitting movement of the inner conductor/insulating support assembly axially along the corrugated outer conductor without radial displacement. The transport device includes two movable contacts, such as skids or rollers, supported on a common pivot lever, the pivot lever being rotatably disposed about a pivot lever axis, which pivot lever axis is in turn disposed on the periphery of a support insulator or particle trap if one is used. The movable contacts are separated axially a distance equal to the axial distance between the peaks and valleys of the corrugations of the outer conductor and separated radially a distance equal to the radial distance between the peaks and valleys of the corrugations of the outer conductor. The transport device has the pivot lever axis disposed perpendicular to the direction of travel of the inner conductor/insulating support assembly.
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Increased sign-tracking behavior in adolescent rats.
DeAngeli, Nicole E; Miller, Sarah B; Meyer, Heidi C; Bucci, David J
2017-11-01
An autoshaping procedure was used to test the notion that conditioned stimuli (CSs) gain greater incentive salience during adolescence than young adulthood under conditions of social isolation rearing and food restriction. Rats were single-housed and placed on food restriction during 10 daily training sessions in which a lever (CS + ) was presented then followed immediately by a food unconditioned stimulus (US). A second lever (CS - ) was presented on intermixed trials and was not reinforced. Despite the fact that food delivery was not contingent on the rats' behavior, all rats exhibited behaviors directed towards the lever (i.e., sign-tracking). In the adolescent group, the rate of lever pressing and the percentage of trials with a lever press were higher than in young adults. Initially, group differences were observed when rats were retrained when the adolescents had reached young adulthood. These findings support the hypothesis that cues that come to predict reward become imbued with excessive motivational value in adolescents, perhaps contributing to the hyper-responsiveness to reward-related stimuli typically observed during this period of development. © 2017 Wiley Periodicals, Inc.
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Belke, Terry W; Garland, Theodore
2007-09-01
Mice from replicate lines, selectively bred based on high daily wheel-running rates, run more total revolutions and at higher average speeds than do mice from nonselected control lines. Based on this difference it was assumed that selected mice would find the opportunity to run in a wheel a more efficacious consequence. To assess this assumption within an operant paradigm, mice must be trained to make a response to produce the opportunity to run as a consequence. In the present study an autoshaping procedure was used to compare the acquisition of lever pressing reinforced by the opportunity to run for a brief opportunity (i.e., 90 s) between selected and control mice and then, using an operant procedure, the effect of the duration of the opportunity to run on lever pressing was assessed by varying reinforcer duration over values of 90 s, 30 min, and 90 s. The reinforcement schedule was a ratio schedule (FR 1 or VR 3). Results from the autoshaping phase showed that more control mice met a criterion of responses on 50% of trials. During the operant phase, when reinforcer duration was 90 s, almost all control, but few selected mice completed a session of 20 reinforcers; however, when reinforcer duration was increased to 30 min almost all selected and control mice completed a session of 20 reinforcers. Taken together, these results suggest that selective breeding based on wheel-running rates over 24 hr may have altered the motivational system in a way that reduces the reinforcing value of shorter running durations. The implications of this finding for these mice as a model for attention deficit hyperactivity disorder (ADHD) are discussed. It also is proposed that there may be an inherent trade-off in the motivational system for activities of short versus long duration.
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Belke, Terry W; GarlandJr, Theodore
2007-01-01
Mice from replicate lines, selectively bred based on high daily wheel-running rates, run more total revolutions and at higher average speeds than do mice from nonselected control lines. Based on this difference it was assumed that selected mice would find the opportunity to run in a wheel a more efficacious consequence. To assess this assumption within an operant paradigm, mice must be trained to make a response to produce the opportunity to run as a consequence. In the present study an autoshaping procedure was used to compare the acquisition of lever pressing reinforced by the opportunity to run for a brief opportunity (i.e., 90 s) between selected and control mice and then, using an operant procedure, the effect of the duration of the opportunity to run on lever pressing was assessed by varying reinforcer duration over values of 90 s, 30 min, and 90 s. The reinforcement schedule was a ratio schedule (FR 1 or VR 3). Results from the autoshaping phase showed that more control mice met a criterion of responses on 50% of trials. During the operant phase, when reinforcer duration was 90 s, almost all control, but few selected mice completed a session of 20 reinforcers; however, when reinforcer duration was increased to 30 min almost all selected and control mice completed a session of 20 reinforcers. Taken together, these results suggest that selective breeding based on wheel-running rates over 24 hr may have altered the motivational system in a way that reduces the reinforcing value of shorter running durations. The implications of this finding for these mice as a model for attention deficit hyperactivity disorder (ADHD) are discussed. It also is proposed that there may be an inherent trade-off in the motivational system for activities of short versus long duration. PMID:17970415
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29 CFR 1918.53 - Cargo winches.
Code of Federal Regulations, 2010 CFR
2010-07-01
... control levers operate with excessive friction or excessive play. (c) Double gear winches or other winches... left unattended, control levers shall be placed in the neutral position and the power shall be shut off...
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NASA Technical Reports Server (NTRS)
Musgrave, Jeffrey L.
1997-01-01
General aviation research is leading to major advances in internal combustion engine control systems for single-engine, single-pilot aircraft. These advances promise to increase engine performance and fuel efficiency while substantially reducing pilot workload and increasing flight safety. One such advance is a single-lever power control (SLPC) system, a welcome departure from older, less user-friendly, multilever engine control systems. The benefits of using single-lever power controls for general aviation aircraft are improved flight safety through advanced engine diagnostics, simplified powerplant operations, increased time between overhauls, and cost-effective technology (extends fuel burn and reduces overhaul costs). The single-lever concept has proven to be so effective in preliminary studies that general aviation manufacturers are making plans to retrofit current aircraft with the technology and are incorporating it in designs for future aircraft.
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Time-Course of the Ethanol-like Discriminative Stimulus Effects of Abused Inhalants in Mice
Bowen, Scott E.
2009-01-01
Abused solvents have effects similar to those of abused depressant drugs. This experiment evaluated the time course of the discriminative stimulus effects of toluene and 1,1,1-trichloroethane (TRI). Mice were trained to discriminate between i.p. injections of ethanol (EtOH;1.25 g/kg) and saline in a two-lever operant task in which responding was under the control of a fixed-ratio 20 schedule. After 20-min inhalation exposures to toluene (500–6000 ppm) or TRI (1,000–12,000 ppm), stimulus generalization was examined at 0, 5, 10, 20, and 40 min post-exposure. Ethanol doses ≥ 0.25 g/kg produced increases in EtOH-lever responding with full substitution occurring immediately after testing for doses between 1.25 and 2.5 g/kg. Toluene and TRI produced increased EtOH-lever responding at 0–10 min post exposure with some EtOH-lever responding occurring up to 20-min post exposure. Response rates were not decreased for any concentration of toluene or TRI immediately following inhalant exposure but several concentrations elevated rates from 5–40 min post exposure. These results confirm and extend previous studies and show these solvents produce similar effects in EtOH-lever responding but with potency differences. The time-dependent differences in EtOH-lever responding suggest that as solvents are cleared from the body, the EtOH-like subjective effects also fade. PMID:18722399
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Effects of orbitofrontal cortex lesions on autoshaped lever pressing and reversal learning.
Chang, Stephen E
2014-10-15
A cue associated with a rewarding event can trigger behavior towards the cue itself due to the cue acquiring incentive value through its pairing with the rewarding outcome (i.e., sign-tracking). For example, rats will approach, press, and attempt to "consume" a retractable lever conditioned stimulus (CS) that signals delivery of a food unconditioned stimulus (US). Attending to food-predictive CSs is important when seeking out food, and it is just as important to be able to modify one's behavior when the relationships between CSs and USs are changed. Using a discriminative autoshaping procedure with lever CSs, the present study investigated the effects of orbitofrontal cortex (OFC) lesions on sign-tracking and reversal learning. Insertion of one lever was followed by sucrose delivery upon retraction, and insertion of another lever was followed by nothing. After the acquisition phase, the contingencies between the levers and outcomes were reversed. Bilateral OFC lesions had no effect on the acquisition of sign-tracking. However, OFC-lesioned rats showed substantial deficits in acquiring sign-tracking compared to sham-lesioned rats once the stimulus-outcome contingencies were reversed. Over the course of reversal learning, OFC-lesioned rats were able to reach comparable levels of sign-tracking as sham-lesioned rats. These findings suggest that OFC is not necessary for the ability of a CS to acquire incentive value and provide more evidence that OFC is critical for modifying behavior appropriately following a change in stimulus-outcome contingencies. Copyright © 2014 Elsevier B.V. All rights reserved.
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Autoshaping, random control, and omission training in the rat1
Locurto, Charles; Terrace, H. S.; Gibbon, John
1976-01-01
The role of the stimulus-reinforcer contingency in the development and maintenance of lever contact responding was studied in hooded rats. In Experiment I, three groups of experimentally naive rats were trained either on autoshaping, omission training, or a random-control procedure. Subjects trained by the autoshaping procedure responded more consistently than did either random-control or omission-trained subjects. The probability of at least one lever contact per trial was slightly higher in subjects trained by the omission procedure than by the random-control procedure. However, these differences were not maintained during extended training, nor were they evident in total lever-contact frequencies. When omission and random-control subjects were switched to the autoshaping condition, lever contacts increased in all animals, but a pronounced retardation was observed in omission subjects relative to the random-control subjects. In addition, subjects originally exposed to the random-control procedure, and later switched to autoshaping, acquired more rapidly than naive subjects that were exposed only on the autoshaping procedure. In Experiment II, subjects originally trained by an autoshaping procedure were exposed either to an omission, a random-control, or an extinction procedure. No differences were observed among the groups either in the rate at which lever contacts decreased or in the frequency of lever contacts at the end of training. These data implicate prior experience in the interpretation of omission-training effects and suggest limitations in the influence of stimulus-reinforcer relations in autoshaping. PMID:16811960
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Autoshaping, random control, and omission training in the rat.
Locurto, C; Terrace, H S; Gibbon, J
1976-11-01
The role of the stimulus-reinforcer contingency in the development and maintenance of lever contact responding was studied in hooded rats. In Experiment I, three groups of experimentally naive rats were trained either on autoshaping, omission training, or a random-control procedure. Subjects trained by the autoshaping procedure responded more consistently than did either random-control or omission-trained subjects. The probability of at least one lever contact per trial was slightly higher in subjects trained by the omission procedure than by the random-control procedure. However, these differences were not maintained during extended training, nor were they evident in total lever-contact frequencies. When omission and random-control subjects were switched to the autoshaping condition, lever contacts increased in all animals, but a pronounced retardation was observed in omission subjects relative to the random-control subjects. In addition, subjects originally exposed to the random-control procedure, and later switched to autoshaping, acquired more rapidly than naive subjects that were exposed only on the autoshaping procedure. In Experiment II, subjects originally trained by an autoshaping procedure were exposed either to an omission, a random-control, or an extinction procedure. No differences were observed among the groups either in the rate at which lever contacts decreased or in the frequency of lever contacts at the end of training. These data implicate prior experience in the interpretation of omission-training effects and suggest limitations in the influence of stimulus-reinforcer relations in autoshaping.
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Fischer, William H.
1984-01-01
A gas-insulated transmission line includes a corrugated outer conductor, an inner conductor disposed within and insulated from the outer conductor by means of support insulators and an insulating gas, and a non-binding transport device for supporting and permitting movement of the inner conductor/insulating support assembly axially along the corrugated outer conductor without radial displacement and for moving without binding along corrugations of any slope less than vertical. The transport device includes two movable contacts, such as skids or rollers, supported on a common pivot lever, the pivot lever being rotatably disposed about a pivot lever axis, which pivot lever axis is in turn disposed on the periphery of a support insulator or particle trap if one is used. The movable contacts are separated axially a distance equal to the axial distance between the peaks and valleys of the corrugations of the outer conductor and separated radially a distance equal to the radial distance between the peaks and valleys of the corrugations of the outer conductor. The transport device has the pivot lever axis disposed parallel to the motion of travel of the inner conductor/insulating support assembly.
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Sederholm, Fredrik; Swedberg, Michael D B
2013-05-13
Rats were trained in a two lever food reinforced operant procedure to discriminate a 8000 Hz pure tone stimulus from its absence. Responding on one lever was reinforced in the presence of the tone and responding on the other lever was reinforced when the tone was absent. Frequency generalization testing yielded an inverted U-shaped function, whereas sound pressure level generalization testing yielded a continuous decrease in responding on the tone associated lever with decreasing sound pressure levels. The administration of sodium salicylic acid (150-450 mg/kg) generated responding on the tone associated lever suggesting that salicylic acid induced an experience that had commonalities with the percept of the training tone stimulus. After exposure to intense sound, responding consistent with the presence of tinnitus was achieved and Lidocaine failed to reduce tinnitus behavior. The use of a two choice design helped avoid confounding factors induced by drug induced side effects. Further, since no auditory cues were employed in the test situation the model achieves resistance to potential bias due to hearing impairment and hyperacusis. We propose that this model may be useful in detecting tinnitus. Copyright © 2013 Elsevier B.V. All rights reserved.
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Sparber, S B; Bollweg, G L; Messing, R B
1991-02-01
The influence of food deprivation on acquisition of autoshaped operant behavior was measured. In one study separate groups of young, male rats that were deprived to 75%, 80%, 85%, 90%, and 95% of ad lib weight were subjected to an autoshaping procedure in which a 6 s delay was interposed between lever retraction (which occurred when rats made a lever touch, or automatically after 15 s) and food pellet delivery. In a second study, groups of rats were deprived to 80% or 90% of ad lib weight prior to testing in a latent inhibition variation of the same autoshaping procedure. This was done to determine if greater food deprivation would enhance learning which, because of the latent inhibition manipulation, is manifest as less lever-directed behavior. Greater food deprivation was associated both with fast acquisition of autoshaped lever responding and with more reliable failure to increase lever responding in the latent inhibition paradigm. Thus, increasing food deprivation was associated with enhanced acquisition regardless of whether the required performance was an increase or a failure to increase the same behavior, indicating a specific effect on learning. Copyright © 1991. Published by Elsevier B.V.
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NASA Astrophysics Data System (ADS)
Liu, Zengjun; Wang, Lei; Li, Kui; Gao, Jiaxin
2017-05-01
Hybrid inertial navigation system (HINS) is a new kind of inertial navigation system (INS), which combines advantages of platform INS, strap-down INS and rotational INS. HINS has a physical platform to isolate the angular motion as platform INS does, HINS also uses strap-down attitude algorithms and applies rotation modulation technique. Tri-axis HINS has three gimbals to isolate the angular motion in the dynamic base, in which way the system can reduce the effects of angular motion and improve the positioning precision. However, the angular motion will affect the compensation of some error parameters, especially for the lever arm effect. The lever arm effect caused by position errors between the accelerometers and rotation center cannot be ignored due to the rapid rotation of inertial measurement unit (IMU) and it will cause fluctuation and stage in velocity in HINS. The influences of angular motion on the lever arm effect compensation are analyzed firstly in this paper, and then the compensation method of lever arm effect based on the photoelectric encoders in dynamic base is proposed. Results of experiments on turntable show that after compensation, the fluctuations and stages in velocity curve disappear.
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35. END VIEW, INTERIOR, SHOWING SWITCHING LEVERS, BERK SWITCH TOWER, ...
35. END VIEW, INTERIOR, SHOWING SWITCHING LEVERS, BERK SWITCH TOWER, SOUTH NORWALK - New York, New Haven & Hartford Railroad, Automatic Signalization System, Long Island Sound shoreline between Stamford & New Haven, Stamford, Fairfield County, CT
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[What kind of communication in the prosumers' era?].
Stancati, M
2010-01-01
The constant interconnection has altered some communicational rhythms and the relation between deepening, reflection and open expression of one's own opinions. What it is said in the different communities in the web can amplify or destroy an expensive advertising campaign or a campaign to prevent work injuries. However, it is very hard to do well in communicating "outside" the company if you do not communicate well "inside" the organisation. A shift from a communication "towards the inside" to an "internal" communication, thought as a strategic lever to share knowledge is needed. But the market, where the so-called "prosumer" increasingly emerges, does make no concessions and penalises those who do not succeed in conforming themselves to the new relational models.
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Transport Signatures of Quasiparticle Poisoning in a Majorana Island.
Albrecht, S M; Hansen, E B; Higginbotham, A P; Kuemmeth, F; Jespersen, T S; Nygård, J; Krogstrup, P; Danon, J; Flensberg, K; Marcus, C M
2017-03-31
We investigate effects of quasiparticle poisoning in a Majorana island with strong tunnel coupling to normal-metal leads. In addition to the main Coulomb blockade diamonds, "shadow" diamonds appear, shifted by 1e in gate voltage, consistent with transport through an excited (poisoned) state of the island. Comparison to a simple model yields an estimate of parity lifetime for the strongly coupled island (∼1 μs) and sets a bound for a weakly coupled island (>10 μs). Fluctuations in the gate-voltage spacing of Coulomb peaks at high field, reflecting Majorana hybridization, are enhanced by the reduced lever arm at strong coupling. When converted from gate voltage to energy units, fluctuations are consistent with previous measurements.
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DeNoble, Victor J; Mele, Paul C
2006-03-01
The rate and pattern of lever pressing were studied in 18 rats during 24-h sessions in which responding resulted in intravenous infusions of nicotine. There were four indications of the positive reinforcing effect of nicotine: (1) a greater number of lever presses when nicotine was response-contingent compared to when saline was available; (2) a greater number of responses on the lever resulting in an infusion of nicotine than on the control lever; (3) systematic decreases in the number of contingent nicotine infusions when nicotine was delivered noncontingently; and (4) systematic changes in the frequency of lever pressing as a function of dose. Under a fixed ratio 1 (FR 1) schedule, the number of infusions first increased and then decreased as the dose of nicotine was decreased (64, 32, 16, and 8 microg/kg infusion) and nicotine intake (mg/kg every 24 h) was directly related to the infusion dose. As the FR size was increased from 1 to 6, the number of lever presses increased and the number of infusions (32 microg/kg) remained stable. At FR values greater than 6, both the number of lever presses and infusions decreased. Presession injections of mecamylamine (0.75, 1.5, and 3.0 mg/kg, s.c.) decreased the number of infusions in a dose-related manner. Presession injections of hexamethonium (1.5 and 3.0 mg/kg, s.c.) or naloxone (0.75, 1.5, and 3.0 mg/kg, s.c.) did not alter the within- or between-session patterns of nicotine self-administration. Under the conditions of the present experiment, nicotine served as an effective reinforcer and the behavior was shown to be sensitive to both FR size and infusion dose. In addition, the results suggest that nicotine self-administration involves central nicotinic receptors and that opioid receptor antagonism has no effect on nicotine's reinforcing effects in rats.
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Orbitofrontal Cortical Neurons Encode Expectation-Driven Initiation of Reward-Seeking
Aston-Jones, Gary
2014-01-01
Adaptive execution and inhibition of behavior are guided by the activity of neuronal populations across multiple frontal cortical areas. The rodent medial prefrontal cortex has been well studied with respect to these behaviors, influencing behavioral execution/inhibition based on context. Other frontal regions, in particular the orbitofrontal cortex (OFC), are critical in directing behavior to obtain rewards, but the relationship between OFC neuronal activity and response execution or inhibition has been poorly characterized. In particular, little is known about OFC with respect to extinction learning, an important example of context-guided response inhibition. Here, we recorded the activity of OFC neurons while rats performed a discriminative-stimulus (DS)-driven sucrose-seeking task followed by multiple days of extinction of the DS. OFC neuronal activity was maximally responsive (1) to reward-predicting stimuli (RS) that triggered a lever press (i.e., lever-response initiation) and (2) during reward-well approach in pursuit of sucrose (i.e., well-response initiation). RS presentation that was not followed by a lever press or RS presentation during extinction produced weak activation, as did nonrewarded stimulus (NS) presentation regardless of response (press or withhold) or session (DS-sucrose or extinction). Activity related to nonrewarded well entry was minor, and activity was significantly inhibited during reward consumption. Finally, OFC neuronal activity switched selectivity to track rewarded behaviors when the RS/NS contingencies were reversed. Thus, rather than signaling variables related to extinction or response inhibition, activity in OFC was strongest at the initiation of multiple components of reward-seeking behavior, most prominently when valid reward-predicting cues drove these behaviors. PMID:25080585
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Employee motivation: a powerful new model.
Nohria, Nitin; Groysberg, Boris; Lee, Linda-Eling
2008-01-01
Motivating employees begins with recognizing that to do their best work, people must be in an environment that meets their basic emotional drives to acquire, bond, comprehend, and defend. So say Nohria and Groysberg, of Harvard Business School, and Lee, of the Center for Research on Corporate Performance. Using the results of surveys they conducted with employees at a wide range of Fortune 500 and other companies, they developed a model for how to increase workplace motivation dramatically. The authors identify the organizational levers that companies and frontline managers have at their disposal as they try to meet workers' deep needs. Reward systems that truly value good performance fulfill the drive to acquire. The drive to bond is best met by a culture that promotes collaboration and openness. Jobs that are designed to be meaningful and challenging meet the need to comprehend. Processes for performance management and resource allocation that are fair, trustworthy, and transparent address the drive to defend. Equipped with real-world company examples, the authors articulate how to apply these levers in productive ways. That application should not be selective, they argue, because a holistic approach gets you more than a piecemeal one. By using all four levers simultaneously, and thereby tackling all four drives, organizations can improve motivation levels by leaps and bounds. For example, a company that falls in the 50th percentile on employee motivation improves only to the 56th by boosting performance on one drive, but way up to the 88th percentile by doing better on all four drives. That's a powerful gain in competitive advantage that any business would relish.
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Responding for sucrose and wheel-running reinforcement: effect of body weight manipulation.
Belke, Terry W
2004-02-27
As body weight increases, the excitatory strength of a stimulus signaling an opportunity to run should weaken to a greater degree than that of a stimulus signaling an opportunity to eat. To test this hypothesis, six male albino Wistar rats were placed in running wheels and exposed to a fixed interval 30-s schedule that produced either a drop of 15% sucrose solution or the opportunity to run for 15s as reinforcing consequences for lever pressing. Each reinforcer type was signaled by a different stimulus. The effect of varying body weight on responding maintained by these two reinforcers was investigated by systematically increasing and decreasing post-session food amounts. The initial body weight was 335 g. Body weights were increased to approximately 445 g and subsequently returned to 335 g. As body weight increased, overall and local lever-pressing rates decreased while post-reinforcement pauses lengthened. Analysis of post-reinforcement pauses and local lever-pressing rates in terms of transitions between successive reinforcers revealed that local response rates in the presence of stimuli signaling upcoming wheel and sucrose reinforcers were similarly affected. However, pausing in the presence of the stimulus signaling a wheel-running reinforcer lengthened to a greater extent than did pausing in the presence of the stimulus signaling sucrose. This result suggests that as body weight approaches ad-lib levels, the likelihood of initiation of responding to obtain an opportunity to run approaches zero and the animal "rejects" the opportunity to run in a manner similar to the rejection of less preferred food items in studies of food selectivity.
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The hippocampus, time and working memory.
Rawlins, J N; Tsaltas, E
1983-12-01
Rats were trained on a discrete trial working memory leverpress alternation task, following hippocampal lesions (HC), cortical control lesions (CC) or sham operations (SO). Each trial consisted of a forced information response, for which a randomly selected lever was presented followed by a free choice stage, when both levers were presented. The rats were rewarded for pressing the lever which had not been presented at the information stage. When the information response was not rewarded, all rats learnt the task equally well at IRIs of up to 12.75 sec. When the information response was rewarded, the HC rats showed impaired choice accuracy. The extent of this impairment depended on the IRI, being greatest at long IRIs, and least at short ones. Varying the number of leverpresses required to complete the information response affected choice accuracy equivalently in all groups: all rats chose significantly less accurately when only one leverpress was required than when ten leverpresses were required. There was no interaction between the lesion treatments and the information response requirements. It was concluded that both the length of the IRI and the occurrence of events during the IRI determine the extent of the hippocampal lesion-induced performance deficit in working memory tasks. It is proposed that hippocampal damage disrupts an intermediate-term, high-capacity memory buffer, but leaves both a residual short-term memory system and the long-term retention of associations unaffected. This proposal leads to the prediction that reference memory tasks should also be affected by hippocampal lesions when a delay is introduced between making a response and being rewarded for doing so.
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Day, Jeremy J; Wheeler, Robert A; Roitman, Mitchell F; Carelli, Regina M
2006-03-01
Environmental stimuli predictive of appetitive events can elicit Pavlovian approach responses that enhance an organism's ability to track and secure natural rewards, but may also contribute to the compulsive nature of drug addiction. Here, we examined the activity of individual nucleus accumbens (NAc) neurons during an autoshaping paradigm. One conditioned stimulus (CS+, a retractable lever presented for 10 s) was immediately followed by the delivery of a 45-mg sucrose pellet to a food receptacle, while another stimulus (CS-, a separate retractable lever presented for 10 s) was never followed by sucrose. Approach responses directed at the CS+ and CS- were recorded as lever presses and had no experimental consequence. Rats (n = 9) selectively approached the CS+ on more than 80% of trials and were surgically prepared for electrophysiological recording. Of 76 NAc neurons, 57 cells (75%) exhibited increases and/or decreases in firing rate (i.e. termed 'phasically active') during the CS+ presentation and corresponding approach response. Forty-seven percent of phasically active cells (27 out of 57) were characterized by time-locked but transient increases in cell firing, while 53% (30 out of 57) showed a significant reduction in firing for the duration of the CS+. In contrast, the same excitatory subpopulation exhibited smaller increases in activity relative to CS- onset, while the inhibitory subpopulation showed no change in firing during the CS- period. The magnitude and prevalence of cue-related neural responses reported here indicates that the NAc encodes biologically significant, repetitive approach responses that may model the compulsive nature of drug addiction in humans.
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Jarmolowicz, David P; Sofis, Michael J; Darden, Alexandria C
2016-07-01
Although progressive ratio (PR) schedules have been used to explore effects of a range of reinforcer parameters (e.g., magnitude, delay), effects of reinforcer probability remain underexplored. The present project used independently progressing concurrent PR PR schedules to examine effects of reinforcer probability on PR breakpoint (highest completed ratio prior to a session terminating 300s pause) and response allocation. The probability of reinforcement on one lever remained at 100% across all conditions while the probability of reinforcement on the other lever was systematically manipulated (i.e., 100%, 50%, 25%, 12.5%, and a replication of 25%). Breakpoints systematically decreased with decreasing reinforcer probabilities while breakpoints on the control lever remained unchanged. Patterns of switching between the two levers were well described by a choice-by-choice unit price model that accounted for the hyperbolic discounting of the value of probabilistic reinforcers. Copyright © 2016 Elsevier B.V. All rights reserved.
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1981-07-01
causes a response of the cardio-pulmonary functions similar to that induced by treadmill and bicycle ergometer exercise (89,90). Therefore, a measure of...Flow, and the Blood Pressure and Heart Rate Response to Isometric Exercise . Saint Louis Uni., AFOSR- TR-75-0086, 1974. 51. T.M. PRINTY. A...relationship between the muscle or muscle group and the corresponding lever system responsible for a given movement. Second, the restrictions of the
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Hauser, S R; Deehan, G A; Dhaher, R; Knight, C P; Wilden, J A; McBride, W J; Rodd, Z A
2015-06-04
Clinical and preclinical research suggest that activation of the mesolimbic dopamine (DA) system is involved in mediating the rewarding actions of drugs of abuse, as well as promoting drug-seeking behavior. Inhibition of DA D1 receptors in the nucleus accumbens (Acb) can reduce ethanol (EtOH)-seeking behavior of non-selective rats triggered by environmental context. However, to date, there has been no research on the effects of D1 receptor agents on EtOH- seeking behavior of high alcohol-preferring (P) rats following prolonged abstinence. The objective of the present study was to examine the effects of microinjecting the D1 antagonist SCH 23390 or the D1 agonist A-77636 into the Acb shell or Acb core on spontaneous recovery of EtOH-seeking behavior. After 10 weeks of concurrent access to EtOH and water, P rats underwent seven extinction sessions (EtOH and water withheld), followed by 2 weeks in their home cages without access to EtOH or operant sessions. In the 2nd week of the home cage phase, rats were bilaterally implanted with guide cannula aimed at the Acb shell or Acb core; rats were allowed 7d ays to recover before EtOH-seeking was assessed by the Pavlovian Spontaneous Recovery (PSR) model. Administration of SCH23390 (1μg/side) into the Acb shell inhibited responding on the EtOH lever, whereas administration of A-77636 (0.125μg/side) increased responding on the EtOH lever. Microinfusion of D1 receptor agents into the Acb core did not alter responding on the EtOH lever. Responses on the water lever were not altered by any of the treatments. The results suggest that activation of D1 receptors within the Acb shell, but not Acb core, are involved in mediating PSR of EtOH-seeking behavior of P rats. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.
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Rodd-Henricks, Z A; McKinzie, D L; Crile, R S; Murphy, J M; McBride, W J
2000-04-01
Because current findings indicate that the selectively bred alcohol-preferring P line of rats self-administers 50-200 mg% ethanol (EtOH) directly into the ventral tegmental area (VTA), whereas the alcohol-nonpreferring NP line does not, it is important to determine whether unselected, common stock rats would self-administer EtOH directly into the VTA. In addition, because neuroanatomical and self-administration studies indicate that the VTA may be functionally heterogeneous, the present study was designed to determine whether there were subregional differences within the VTA for the intracranial self-administration (ICSA) of EtOH. The objective of this study was to employ the ICSA technique to determine whether adult female Wistar rats would self-administer EtOH directly into the VTA, and whether regional heterogeneity existed for EtOH self-infusion within the VTA. Following surgery to implant guide cannulae aimed at either the posterior or anterior VTA, subjects were placed in standard experimental chambers equipped with an 'active lever' [fixed ratio (FR)1 schedule of reinforcement], which caused the delivery of the infusate, and an 'inactive lever', which had no programmed consequence. Subjects were assigned to groups that self-administered either artificial cerebrospinal fluid (aCSF) throughout, or 100-400 mg% EtOH for the first four sessions (acquisition), aCSF in sessions 5 and 6 (extinction), and EtOH again during session 7 (reinstatement). During the four acquisition sessions, rats with posterior VTA placements readily self-administered 200 mg% and 250 mg% EtOH and discriminated between the active and inactive levers. These subjects also demonstrated extinction, when aCSF was substituted for EtOH, and reinstatement when EtOH was reintroduced. Rats with posterior VTA placements self-infused 300 mg% and 400 mg% EtOH, and demonstrated lever discrimination only during the initial acquisition sessions. In contrast, rats with anterior VTA placements did not self-administer EtOH. The findings suggest that EtOH is reinforcing within the posterior VTA of Wistar rats, and the VTA is a functionally heterogeneous structure with regard to EtOH reinforcement.
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Code of Federal Regulations, 2010 CFR
2010-01-01
... 1444 of NARETPA or under sections 3(b) and (c) of the Smith-Lever Act, 7 U.S.C. 343(b) and (c... cooperative extension under sections 1444 and 1445 of NARETPA, the Hatch Act of 1887, and the Smith-Lever Act...
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Fabre, P-H; Herrel, A; Fitriana, Y; Meslin, L; Hautier, L
2017-09-01
Murines are well known for their generalist diet, but several of them display specializations towards a carnivorous diet such as the amphibious Indo-Pacific water-rats. Despite the fact that carnivory evolved repeatedly in this group, few studies have investigated associated changes in jaw muscle anatomy and biomechanics. Here, we describe the jaw muscles and cranial anatomy of a carnivorous water-rat, Hydromys chrysogaster. The architecture of the jaw musculature of six specimens captured both on Obi and Papua were studied and described using dissections. We identified the origin and insertions of the jaw muscles, and quantified muscle mass, fiber length, physiological cross-sectional area, and muscle vectors for each muscle. Using a biomechanical model, we estimated maximum incisor and molar bite force at different gape angles. Finally, we conducted a 2D geometric morphometric analyses to compare jaw shape, mechanical potential, and diversity in lever-arm ratios for a set of 238 specimens, representative of Australo-Papuan carnivorous and omnivorous murids. Our study reveals major changes in the muscle proportions among Hydromys and its omnivorous close relative, Melomys. Hydromys was found to have large superficial masseter and temporalis muscles as well as a reduced deep masseter and zygomatico-mandibularis, highlighting major functional divergence among omnivorous and carnivorous murines. Changes in these muscles are also accompanied by changes in jaw shape and the lines of action of the muscles. A more vertically oriented masseter, reduced masseteric muscles, as well as an elongated jaw with proodont lower incisors are key features indicative of a reduced propalinality in carnivorous Hydromys. Differences in the fiber length of the masseteric muscles were also detected between Hydromys and Melomys, which highlight potential adaptations to a wide gape in Hydromys, allowing it to prey on larger animals. Using a biomechanical model, we inferred a greater bite force in Hydromys than in Melomys, implying a functional shift between omnivory and carnivory. However, Melomys has an unexpected greater bite force at large gape compared with Hydromys. Compared with omnivorous Melomys, Hydromys have a very distinctive low mandible with a well-developed coronoid process, and a reduced angular process that projects posteriorly to the ascending rami. This jaw shape, along with our mechanical potential and jaw lever ratio estimates, suggests that Hydromys has a faster jaw closing at the incisor, with a higher bite force at the level of the molars. The narrowing of the Hydromys jaw explains this higher lever advantage at the molars, which constitutes a good compromise between a wide gape, a reduced anterior masseteric mass, and long fiber lengths. Lever arms of the superficial and deep masseter are less favourable to force output of the mandible in Hydromys but more favourable to speed. Compared with the small input lever arm defined between the condyle and the angular process, the relatively longer mandible of Hydromys increases the speed at the expense of the output force. This unique combination of morphological features of the masticatory apparatus possibly has permitted Hydromys to become a highly successful amphibious predator in the Indo-Pacific region. © 2017 Anatomical Society.
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Method and system for dual resolution translation stage
Halpin, John Michael
2014-04-22
A dual resolution translation stage includes a stage assembly operable to receive an optical element and a low resolution adjustment device mechanically coupled to the stage assembly. The dual resolution stage also includes an adjustable pivot block mechanically coupled to the stage assembly. The adjustable pivot block includes a pivot shaft. The dual resolution stage further includes a lever arm mechanically coupled to the adjustable pivot block. The lever arm is operable to pivot about the pivot shaft. The dual resolution stage additionally includes a high resolution adjustment device mechanically coupled to the lever arm and the stage assembly.
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Kinetics of cross-slope running.
Willwacher, Steffen; Fischer, Katina Mira; Benker, Rita; Dill, Stephan; Brüggemann, Gert-Peter
2013-11-15
The purpose of the present study was to identify kinetic responses to running on mediolaterally elevated (cross-sloped) running surfaces. Ground reaction forces (GRFs), GRF lever arms and joint moment characteristics of 19 male runners were analyzed when running at 3.5m/s on a custom-made, tiltable runway. Tilt angles of 3° and 6° for medial and lateral elevation were analyzed using a 10 camera Vicon Nexus system and a force platform. The point of force application of the GRF showed a systematic shift in the order of 1-1.5cm to either the lateral or medial aspect of the foot for lateral or medial inclinations, respectively. Consequently, the strongest significant effects of tilt orientation and level on joint kinetics and ground reaction force lever arms were identified at the ankle, knee and hip joint in the frontal plane of movement. External eversion moments at the ankle were significantly increased by 35% for 6° of lateral elevation and decreased by 16% for 6° of medial elevation. Altering the cross-slope of the running surface changed the pattern of ankle joint moments in the transversal plane. Effect sizes were on average larger for laterally elevated conditions, indicating a higher sensitivity of kinetic parameters to this kind of surface tilt. These alterations in joint kinetics should be considered in the choice of the running environment, especially for specific risk groups, like runners in rehabilitation processes. © 2013 Elsevier Ltd. All rights reserved.
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Barrett, Robert J; Caul, William F; Smith, Randy
2005-05-01
In the present experiment rats were trained on a three-lever, drug-discrimination task to discriminate the cues associated with 0.30 mg/kg of the indirect dopamine (DA) agonist, amphetamine (AMPH), saline (SAL), and 0.03 mg/kg of the DA, D2 receptor antagonist, haloperidol (HAL). Choice behavior determined from tests on 0.30 and 0.15 mg/kg AMPH, SAL 0.03 and 0.015 mg/kg HAL provided a behavioral baseline presumed to represent changes along a continuum of DA mediated, interoceptive cues. Results from separate groups tested on 0.30 and 0.15 mg/kg AMPH, SAL, 0.03 and 0.015 mg/kg HAL, 24 h post-treatment with an acute 7.5 mg/kg dose of AMPH, showed rapid tolerance and withdrawal to the AMPH cue and sensitization to the HAL cue. The same tests 24 h following treatment with 1.0 mg/kg HAL showed rapid tolerance to the HAL cue, sensitization to the AMPH cue, but not AMPH-like withdrawal cues. Analysis of the results showed that tolerance to the AMPH and HAL cues reflected neuroadaptive baseline shifts and not weaker cue properties. These findings are consistent with predictions from opponent process theory of motivation and provide an animal model to study the motivational consequences that aversive symptoms of AMPH withdrawal such as dysphoria and anhedonia can have on drug-taking behavior.
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Gresch, Paul J; Smith, Randy L; Barrett, Robert J; Sanders-Bush, Elaine
2005-09-01
Tolerance is defined as a decrease in responsiveness to a drug after repeated administration. Tolerance to the behavioral effects of hallucinogens occurs in humans and animals. In this study, we used drug discrimination to establish a behavioral model of lysergic acid diethylamide (LSD) tolerance and examined whether tolerance to the stimulus properties of LSD is related to altered serotonin receptor signaling. Rats were trained to discriminate 60 microg/kg LSD from saline in a two-lever drug discrimination paradigm. Two groups of animals were assigned to either chronic saline treatment or chronic LSD treatment. For chronic treatment, rats from each group were injected once per day with either 130 microg/kg LSD or saline for 5 days. Rats were tested for their ability to discriminate either saline or 60 microg/kg LSD, 24 h after the last chronic injection. Rats receiving chronic LSD showed a 44% reduction in LSD lever selection, while rats receiving chronic vehicle showed no change in percent choice on the LSD lever. In another group of rats receiving the identical chronic LSD treatment, LSD-stimulated [35S]GTPgammaS binding, an index of G-protein coupling, was measured in the rat brain by autoradiography. After chronic LSD, a significant reduction in LSD-stimulated [35S]GTPgammaS binding was observed in the medial prefrontal cortex and anterior cingulate cortex. Furthermore, chronic LSD produced a significant reduction in 2,5-dimethoxy-4-iodoamphetamine-stimulated [35S]GTPgammaS binding in medial prefrontal cortex and anterior cingulate cortex, which was blocked by MDL 100907, a selective 5-HT2A receptor antagonist, but not SB206553, a 5-HT2C receptor antagonist, indicating a reduction in 5-HT2A receptor signaling. 125I-LSD binding to 5-HT2A receptors was reduced in cortical regions, demonstrating a reduction in 5-HT2A receptor density. Taken together, these results indicate that adaptive changes in LSD-stimulated serotonin receptor signaling may mediate tolerance to the discriminative stimulus effects of LSD.
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Well below 2 °C: Mitigation strategies for avoiding dangerous to catastrophic climate changes
NASA Astrophysics Data System (ADS)
Xu, Yangyang; Ramanathan, Veerabhadran
2017-09-01
The historic Paris Agreement calls for limiting global temperature rise to “well below 2 °C.” Because of uncertainties in emission scenarios, climate, and carbon cycle feedback, we interpret the Paris Agreement in terms of three climate risk categories and bring in considerations of low-probability (5%) high-impact (LPHI) warming in addition to the central (˜50% probability) value. The current risk category of dangerous warming is extended to more categories, which are defined by us here as follows: >1.5 °C as dangerous; >3 °C as catastrophic; and >5 °C as unknown, implying beyond catastrophic, including existential threats. With unchecked emissions, the central warming can reach the dangerous level within three decades, with the LPHI warming becoming catastrophic by 2050. We outline a three-lever strategy to limit the central warming below the dangerous level and the LPHI below the catastrophic level, both in the near term (<2050) and in the long term (2100): the carbon neutral (CN) lever to achieve zero net emissions of CO2, the super pollutant (SP) lever to mitigate short-lived climate pollutants, and the carbon extraction and sequestration (CES) lever to thin the atmospheric CO2 blanket. Pulling on both CN and SP levers and bending the emissions curve by 2020 can keep the central warming below dangerous levels. To limit the LPHI warming below dangerous levels, the CES lever must be pulled as well to extract as much as 1 trillion tons of CO2 before 2100 to both limit the preindustrial to 2100 cumulative net CO2 emissions to 2.2 trillion tons and bend the warming curve to a cooling trend.
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Quantifying Social Motivation in Mice Using Operant Conditioning.
Martin, Loren; Iceberg, Erica
2015-08-08
In this protocol, social motivation is measured in mice through a pair of operant conditioning paradigms. To conduct the experiments, two-chambered shuttle boxes were equipped with two operant levers (left and right) and a food receptacle in one chamber, which was then divided from the second chamber by an automated guillotine door covered by a wire grid. Different stimulus mice, rotated across testing days, served as a social stimulus behind the wire grid, and were only visible following the opening of the guillotine door. Test mice were trained to lever press in order to open the door and gain access to the stimulus partner for 15 sec. The number of lever presses required to obtain the social reward progressively increased on a fixed schedule of 3. Testing sessions ended after test mice stopped lever pressing for 5 consecutive minutes. The last reinforced ratio or breakpoint can be used as a quantitative measure of social motivation. For the second paradigm, test mice were trained to discriminate between left and right lever presses in order to obtain either a food reward or the social reward. Mice were rewarded for every 3 presses of each respective lever. The number of food and social rewards can be compared as a measurement of the value placed upon each reward. The ratio of each reward type can also be compared between mouse strains and the change in this ratio can be monitored within testing sessions to measure satiation with a given reward type. Both of these operant conditioning paradigms are highly useful for the quantification of social motivation in mouse models of autism and other disorders of social behavior.
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Stafford, Alexandra M.; Anderson, Shawn M.; Shelton, Keith L.; Brunzell, Darlene H.
2015-01-01
Rationale Mouse models of EtOH self-administration are useful to identify genetic and biological underpinnings of alcohol use disorder. Objectives These experiments developed a novel method of oral operant EtOH self-administration in mice without explicitly paired cues, food/water restriction, or EtOH fading. Methods Following magazine and lever training for 0.2% saccharin (SAC), mice underwent 9 weekly overnight sessions with lever pressing maintained by dipper presentation of 0, 3, 10 or 15% EtOH in SAC or water vehicle. Ad libitum water was available from a bottle. Results Water vehicle mice ingested most fluid from the water bottle in contrast to SAC vehicle mice, which despite lever pressing demands, drank most of their fluid from the liquid dipper. Although EtOH in SAC vehicle mice showed concentration-dependent increases of g/kg EtOH intake, lever pressing decreased with increasing EtOH concentration and did not exceed that of SAC vehicle alone at any EtOH concentration. Mice reinforced with EtOH in water ingested less EtOH than mice reinforced with EtOH in SAC. EtOH in water mice, however, showed concentration-dependent increases in g/kg EtOH intake and lever presses. 15% EtOH in water mice showed significantly greater levels of lever pressing than water vehicle mice and a significant escalation of responding across weeks of exposure. Naltrexone pretreatment reduced EtOH self-administration and intake in these mice without altering responding in the vehicle control condition during the first hour of the session. Conclusions SAC facilitated EtOH intake but prevented observation of EtOH reinforcement. Water vehicle unmasked EtOH's reinforcing effects. PMID:26268145
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Stafford, Alexandra M; Anderson, Shawn M; Shelton, Keith L; Brunzell, Darlene H
2015-10-01
Mouse models of ethanol (EtOH) self-administration are useful to identify genetic and biological underpinnings of alcohol use disorder. These experiments developed a novel method of oral operant EtOH self-administration in mice without explicitly paired cues, food/water restriction, or EtOH fading. Following magazine and lever training for 0.2 % saccharin (SAC), mice underwent nine weekly overnight sessions with lever pressing maintained by dipper presentation of 0, 3, 10, or 15 % EtOH in SAC or water vehicle. Ad libitum water was available from a bottle. Water vehicle mice ingested most fluid from the water bottle in contrast to SAC vehicle mice, which despite lever pressing demands, drank most of their fluid from the liquid dipper. Although EtOH in SAC vehicle mice showed concentration-dependent increases of g/kg EtOH intake, lever pressing decreased with increasing EtOH concentration and did not exceed that of SAC vehicle alone at any EtOH concentration. Mice reinforced with EtOH in water ingested less EtOH than mice reinforced with EtOH in SAC. EtOH in water mice, however, showed concentration-dependent increases in g/kg EtOH intake and lever presses. Fifteen percent EtOH in water mice showed significantly greater levels of lever pressing than water vehicle mice and a significant escalation of responding across weeks of exposure. Naltrexone pretreatment reduced EtOH self-administration and intake in these mice without altering responding in the vehicle control condition during the first hour of the session. SAC facilitated EtOH intake but prevented observation of EtOH reinforcement. Water vehicle unmasked EtOH's reinforcing effects.
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Knupp, Carlo; Offer, Gerald; Ranatunga, K W; Squire, John M
2009-07-10
The key question in understanding how force and movement are produced in muscle concerns the nature of the cyclic interaction of myosin molecules with actin filaments. The lever arm of the globular head of each myosin molecule is thought in some way to swing axially on the actin-attached motor domain, thus propelling the actin filament past the myosin filament. Recent X-ray diffraction studies of vertebrate muscle, especially those involving the analysis of interference effects between myosin head arrays in the two halves of the thick filaments, have been claimed to prove that the lever arm moves at the same time as the sliding of actin and myosin filaments in response to muscle length or force steps. It was suggested that the sliding of myosin and actin filaments, the level of force produced and the lever arm angle are all directly coupled and that other models of lever arm movement will not fit the X-ray data. Here, we show that, in addition to interference across the A-band, which must be occurring, the observed meridional M3 and M6 X-ray intensity changes can all be explained very well by the changing diffraction effects during filament sliding caused by heads stereospecifically attached to actin moving axially relative to a population of detached or non-stereospecifically attached heads that remain fixed in position relative to the myosin filament backbone. Crucially, and contrary to previous interpretations, the X-ray interference results provide little direct information about the position of the myosin head lever arm; they are, in fact, reporting relative motor domain movements. The implications of the new interpretation are briefly assessed.
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Well below 2 °C: Mitigation strategies for avoiding dangerous to catastrophic climate changes.
Xu, Yangyang; Ramanathan, Veerabhadran
2017-09-26
The historic Paris Agreement calls for limiting global temperature rise to "well below 2 °C." Because of uncertainties in emission scenarios, climate, and carbon cycle feedback, we interpret the Paris Agreement in terms of three climate risk categories and bring in considerations of low-probability (5%) high-impact (LPHI) warming in addition to the central (∼50% probability) value. The current risk category of dangerous warming is extended to more categories, which are defined by us here as follows: >1.5 °C as dangerous; >3 °C as catastrophic; and >5 °C as unknown, implying beyond catastrophic, including existential threats. With unchecked emissions, the central warming can reach the dangerous level within three decades, with the LPHI warming becoming catastrophic by 2050. We outline a three-lever strategy to limit the central warming below the dangerous level and the LPHI below the catastrophic level, both in the near term (<2050) and in the long term (2100): the carbon neutral (CN) lever to achieve zero net emissions of CO 2 , the super pollutant (SP) lever to mitigate short-lived climate pollutants, and the carbon extraction and sequestration (CES) lever to thin the atmospheric CO 2 blanket. Pulling on both CN and SP levers and bending the emissions curve by 2020 can keep the central warming below dangerous levels. To limit the LPHI warming below dangerous levels, the CES lever must be pulled as well to extract as much as 1 trillion tons of CO 2 before 2100 to both limit the preindustrial to 2100 cumulative net CO 2 emissions to 2.2 trillion tons and bend the warming curve to a cooling trend. Copyright © 2017 the Author(s). Published by PNAS.
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Determinants of reinforcer accumulation during an operant task.
McFarland, J M; Lattal, K A
2001-11-01
Responses by rats on an earn lever made available food pellets that were delivered to a food cup by responses on a second, collect, lever. The rats could either collect and immediately consume or accumulate (defined as the percentage of multiple earn responses and as the number of pellets earned before a collect response) earned pellets. In Experiment 1, accumulation varied as a function of variations in the earn or collect response requirements and whether the earn and collect levers were proximal (31 cm) or distal (248 cm) to one another. Some accumulation occurred under all but one of the conditions, but generally was higher when the earn and collect levers were distal to one another, particularly when the earn response requirement was fixed-ratio (FR) 1. In Experiment 2, the contributions of responses and time to accumulation were assessed by comparing an FR 20 earn response requirement to a condition in which only a single earn response was required at the end of a time interval nominally yoked to the FR interval. When 248 cm separated the earn and collect levers, accumulation was always greater in the FR condition, and it was not systematically related to reinforcement rate. In Experiment 3, increasing the earn response requirement with a progressive-ratio schedule that reset only with a collect response increased the likelihood of accumulation when the collect and earn levers were 248 cm apart, even though such accumulation increased the next earn response requirement. Reinforcer accumulation is an understudied dimension of operant behavior that relates to the analysis of such phenomena as hoarding and self-control, in that they too involve accumulating versus immediately collecting or consuming reinforcers.
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Determinants of reinforcer accumulation during an operant task.
McFarland, J M; Lattal, K A
2001-01-01
Responses by rats on an earn lever made available food pellets that were delivered to a food cup by responses on a second, collect, lever. The rats could either collect and immediately consume or accumulate (defined as the percentage of multiple earn responses and as the number of pellets earned before a collect response) earned pellets. In Experiment 1, accumulation varied as a function of variations in the earn or collect response requirements and whether the earn and collect levers were proximal (31 cm) or distal (248 cm) to one another. Some accumulation occurred under all but one of the conditions, but generally was higher when the earn and collect levers were distal to one another, particularly when the earn response requirement was fixed-ratio (FR) 1. In Experiment 2, the contributions of responses and time to accumulation were assessed by comparing an FR 20 earn response requirement to a condition in which only a single earn response was required at the end of a time interval nominally yoked to the FR interval. When 248 cm separated the earn and collect levers, accumulation was always greater in the FR condition, and it was not systematically related to reinforcement rate. In Experiment 3, increasing the earn response requirement with a progressive-ratio schedule that reset only with a collect response increased the likelihood of accumulation when the collect and earn levers were 248 cm apart, even though such accumulation increased the next earn response requirement. Reinforcer accumulation is an understudied dimension of operant behavior that relates to the analysis of such phenomena as hoarding and self-control, in that they too involve accumulating versus immediately collecting or consuming reinforcers. PMID:11768714
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Well below 2 °C: Mitigation strategies for avoiding dangerous to catastrophic climate changes
Xu, Yangyang; Ramanathan, Veerabhadran
2017-01-01
The historic Paris Agreement calls for limiting global temperature rise to “well below 2 °C.” Because of uncertainties in emission scenarios, climate, and carbon cycle feedback, we interpret the Paris Agreement in terms of three climate risk categories and bring in considerations of low-probability (5%) high-impact (LPHI) warming in addition to the central (∼50% probability) value. The current risk category of dangerous warming is extended to more categories, which are defined by us here as follows: >1.5 °C as dangerous; >3 °C as catastrophic; and >5 °C as unknown, implying beyond catastrophic, including existential threats. With unchecked emissions, the central warming can reach the dangerous level within three decades, with the LPHI warming becoming catastrophic by 2050. We outline a three-lever strategy to limit the central warming below the dangerous level and the LPHI below the catastrophic level, both in the near term (<2050) and in the long term (2100): the carbon neutral (CN) lever to achieve zero net emissions of CO2, the super pollutant (SP) lever to mitigate short-lived climate pollutants, and the carbon extraction and sequestration (CES) lever to thin the atmospheric CO2 blanket. Pulling on both CN and SP levers and bending the emissions curve by 2020 can keep the central warming below dangerous levels. To limit the LPHI warming below dangerous levels, the CES lever must be pulled as well to extract as much as 1 trillion tons of CO2 before 2100 to both limit the preindustrial to 2100 cumulative net CO2 emissions to 2.2 trillion tons and bend the warming curve to a cooling trend. PMID:28912354
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Buckley, Jessica Lynn; Rasmussen, Erin B.
2014-01-01
Rationale Cannabinoid antagonists purportedly have greater effects in reducing the intake of highly palatable food compared to less palatable food. However, this assertion is based on free-feeding studies in which the amount of palatable food eaten under baseline conditions is often confounded with other variables, such as unequal access to both food options and differences in qualitative features of the foods. Objective We attempted to reduce these confounds by using a model of choice that programmed the delivery rates of sucrose and carrot-flavored pellets. Methods Lever-pressing of ten lean (Fa/Fa or Fa/fa) and ten obese (fa/fa) Zucker rats was placed under three conditions in which programmed ratios for food pellets on two levers were 5:1, 1:1, and 1:5. In Phase 1, responses on the two levers produced one type of pellet (sucrose or carrot); in Phase 2, responses on one lever produced sucrose pellets and on the other lever produced carrot pellets. After responses stabilized under each food ratio, acute doses of rimonabant (0, 3, and 10 mg/kg) were administered before experimental sessions. The number of reinforcers and responses earned per session under each ratio and from each lever was compared. Results and Conclusions Rimonabant reduced reinforcers in 1:5 and 5:1 food ratios in Phase 1, and across all ratios in Phase 2. Rimonabant reduced sucrose and carrot-flavored pellet consumption similarly; rimonabant did not affect bias toward sucrose, but increased sensitivity to amount differences in lean rats. This suggests that relative amount of food, not palatability, may be an important behavioral mechanism in the effects of rimonabant. PMID:24398820
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Buckley, Jessica L; Rasmussen, Erin B
2014-05-01
Cannabinoid antagonists purportedly have greater effects in reducing the intake of highly palatable food compared to less palatable food. However, this assertion is based on free-feeding studies in which the amount of palatable food eaten under baseline conditions is often confounded with other variables, such as unequal access to both food options and differences in qualitative features of the foods. We attempted to reduce these confounds by using a model of choice that programmed the delivery rates of sucrose and carrot-flavored pellets. Lever pressing of ten lean (Fa/Fa or Fa/fa) and ten obese (fa/fa) Zucker rats was placed under three conditions in which programmed ratios for food pellets on two levers were 5:1, 1:1, and 1:5. In phase 1, responses on the two levers produced one type of pellet (sucrose or carrot); in phase 2, responses on one lever produced sucrose pellets and on the other lever produced carrot pellets. After responses stabilized under each food ratio, acute doses of rimonabant (0, 3, and 10 mg/kg) were administered before experimental sessions. The number of reinforcers and responses earned per session under each ratio and from each lever was compared. Rimonabant reduced reinforcers in 1:5 and 5:1 food ratios in phase 1, and across all ratios in phase 2. Rimonabant reduced sucrose and carrot-flavored pellet consumption similarly; rimonabant did not affect bias toward sucrose, but increased sensitivity to amount differences in lean rats. This suggests that relative amount of food, not palatability, may be an important behavioral mechanism in the effects of rimonabant.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Minoda, Hiroki; CREST, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012; Okabe, Tatsuhiro
2011-02-25
Research highlights: {yields} We succeeded in recording structural changes of hydrated myosin cross-bridges. {yields} We succeeded in position-marking the cross-bridges with site-directed antibodies. {yields} We recorded cross-bridge movement at different regions in individual cross-bridge. {yields} The movement was smallest at the cross-bridge-subfragment two boundary. {yields} The results provide evidence for the cross-bridge lever arm mechanism. -- Abstract: Muscle contraction results from an attachment-detachment cycle between the myosin heads extending from myosin filaments and the sites on actin filaments. The myosin head first attaches to actin together with the products of ATP hydrolysis, performs a power stroke associated with release ofmore » hydrolysis products, and detaches from actin upon binding with new ATP. The detached myosin head then hydrolyses ATP, and performs a recovery stroke to restore its initial position. The strokes have been suggested to result from rotation of the lever arm domain around the converter domain, while the catalytic domain remains rigid. To ascertain the validity of the lever arm hypothesis in muscle, we recorded ATP-induced movement at different regions within individual myosin heads in hydrated myosin filaments, using the gas environmental chamber attached to the electron microscope. The myosin head were position-marked with gold particles using three different site-directed antibodies. The amplitude of ATP-induced movement at the actin binding site in the catalytic domain was similar to that at the boundary between the catalytic and converter domains, but was definitely larger than that at the regulatory light chain in the lever arm domain. These results are consistent with the myosin head lever arm mechanism in muscle contraction if some assumptions are made.« less
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Nasser, Helen M; Lafferty, Danielle S; Lesser, Ellen N; Bacharach, Sam Z; Calu, Donna J
2018-01-01
Previously established individual differences in appetitive approach and devaluation sensitivity observed in goal- and sign-trackers may be attributed to differences in the acquisition, modification, or use of associative information in basolateral amygdala (BLA) pathways. Here, we sought to determine the extent to which communication of associative information between BLA and anterior portions of insular cortex (IC) supports ongoing Pavlovian conditioned approach behaviors in sign- and goal-tracking rats, in the absence of manipulations to outcome value. We hypothesized that the BLA mediates goal-, but not sign- tracking approach through interactions with the IC, a brain region involved in supporting flexible behavior. We first trained rats in Pavlovian lever autoshaping to determine their sign- or goal-tracking tendency. During alternating test sessions, we gave unilateral intracranial injections of vehicle or a cocktail of gamma-aminobutyric acid (GABA) receptor agonists, baclofen and muscimol, unilaterally into the BLA and contralaterally or ipsilaterally into the IC prior to reinforced lever autoshaping sessions. Consistent with our hypothesis we found that contralateral inactivation of BLA and IC increased the latency to approach the food cup and decreased the number of food cup contacts in goal-trackers. While contralateral inactivation of BLA and IC did not affect the total number of lever contacts in sign-trackers, this manipulation increased the latency to approach the lever. Ipsilateral inactivation of BLA and IC did not impact approach behaviors in Pavlovian lever autoshaping. These findings, contrary to our hypothesis, suggest that communication between BLA and IC maintains a representation of initially learned appetitive associations that commonly support the initiation of Pavlovian conditioned approach behavior regardless of whether it is directed at the cue or the location of reward delivery. Copyright © 2017 Elsevier Inc. All rights reserved.
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Xue, YueQiang; Steketee, Jeffery D; Sun, WenLin
2012-03-01
Continued cocaine use despite the negative consequences is a hallmark of cocaine addiction. One such consequence is punishment, which is often used by society to curb cocaine use. Unfortunately, we know little about the mechanism involved in regulation by punishment of cocaine use. The fact that cocaine addicts continue to use cocaine despite potentially severe punishment suggests that the mechanism may be impaired. Such impairment is expected to critically contribute to compulsive cocaine use. This study was aimed at testing the hypothesis that the central nucleus of the amygdala (CeN) plays a critical role in such regulation. To this end, rats were trained to press a lever to self-administer cocaine under a chained schedule: a response on one lever (cocaine-seeking lever) led to access to the other lever (cocaine-taking lever), on which a response was reinforced by cocaine and cues. Thereafter, responses on the seeking lever were punished by footshock with a probability of 0.5. Cocaine self-administration (SA) was significantly suppressed by punishment in an intensity-dependent manner. Interestingly, rats trained with daily 6-h (extended access) but not 2-h (limited access) sessions showed resistance to the lower intensity of punishment. Inactivation of the CeN induced a robust anti-punishment effect in both groups. These data provided evidence that the CeN is a critical neural substrate involved in regulation by punishment of cocaine SA. Rats with a history of extended cocaine SA appeared to be less sensitive to punishment. The decreased sensitivity could result from the neuroplastic changes induced by extended cocaine SA in the CeN. © 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.
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Xue, YueQiang; Steketee, Jeffery D.; Sun, WenLin
2012-01-01
Continued cocaine use despite the negative consequences is a hallmark of cocaine addiction. One such consequence is punishment that is often used by society to curb cocaine use. Unfortunately, we know little about the mechanism involved in regulation by punishment of cocaine use. The fact that cocaine addicts continue cocaine use despite potential severe punishment suggests that the mechanism may be impaired. Such impairment is expected to critically contribute to compulsive cocaine use. This study aimed to test the hypothesis that the central nucleus of amygdala (CeN) plays a critical role in such regulation. To this end, rats were trained to press a lever to self-administer cocaine under a chained schedule: a response on one lever (cocaine-seeking lever) led to access to the other lever (cocaine-taking lever) on which a response was reinforced by cocaine and cues. Thereafter, responses on the seeking lever were punished by footshock with a probability of 0.5. Cocaine self-administration (SA) was significantly suppressed by punishment in an intensity-dependent manner. Interestingly, rats trained with daily 6-h (extended access) but not 2-h (limited access) sessions showed resistance to the lower intensity of punishment. Inactivation of the CeN induced a robust anti-punishment effect in both groups. These data provided evidence that the CeN is a critical neural substrate involved in regulation by punishment of cocaine SA. Rats with a history of extended cocaine SA appeared to be less sensitive to punishment. The decreased sensitivity could result from the neuroplastic changes induced by extended cocaine SA in the CeN. PMID:22304754
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NASA Technical Reports Server (NTRS)
Tervo, John N.
1992-01-01
Valve plate made to translate as well as rotate. Valve opened and closed by turning shaft and lever. Interactions among lever, spring, valve plate, and face seal cause plate to undergo combination of translation and rotation so valve plate clears seal during parts of opening and closing motions.
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The structure of affective action representations: temporal binding of affective response codes.
Eder, Andreas B; Müsseler, Jochen; Hommel, Bernhard
2012-01-01
Two experiments examined the hypothesis that preparing an action with a specific affective connotation involves the binding of this action to an affective code reflecting this connotation. This integration into an action plan should lead to a temporary occupation of the affective code, which should impair the concurrent representation of affectively congruent events, such as the planning of another action with the same valence. This hypothesis was tested with a dual-task setup that required a speeded choice between approach- and avoidance-type lever movements after having planned and before having executed an evaluative button press. In line with the code-occupation hypothesis, slower lever movements were observed when the lever movement was affectively compatible with the prepared evaluative button press than when the two actions were affectively incompatible. Lever movements related to approach and avoidance and evaluative button presses thus seem to share a code that represents affective meaning. A model of affective action control that is based on the theory of event coding is discussed.
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Sign-tracking (autoshaping) in rats: a comparison of cocaine and food as unconditioned stimuli.
Kearns, David N; Weiss, Stanley J
2004-11-01
A series of experiments was performed to determine whether sign-tracking would occur in rats with intravenous (i.v.) cocaine as the unconditioned stimulus. In Experiment 1, a retractable lever paired with food produced strong sign-tracking, but a lever paired with one of three doses of i.v. cocaine did not elicit any approach or contact behavior. Experiment 2 demonstrated that doses of cocaine that did not elicit sign-tracking would function as a positive reinforcer for a lever contact operant. In Experiment 3, an artificial consummatory response was added to make the cocaine reinforcement episode more behaviorally comparable to that occasioned by food. Although the rats readily performed this response when it was required to receive cocaine infusions, they still did not contact a lever that signaled the availability of these infusions. It appears that cocaine is different from other positive reinforcers (e.g., food, water, warmth, or intracranial stimulation) in that it will not produce sign-tracking in rats.
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Taukobong, Hannah F G; Kincaid, Mary M; Levy, Jessica K; Bloom, Shelah S; Platt, Jennifer L; Henry, Sarah K; Darmstadt, Gary L
2016-12-01
This article presents evidence supporting the hypothesis that promoting gender equality and women's and girls' empowerment (GEWE) leads to better health and development outcomes. We reviewed the literature across six sectors-family planning (FP); maternal, newborn and child health (MNCH); nutrition; agriculture; water, sanitation and hygiene; and financial services for the poor-and found 76 studies from low and middle-income countries that met our inclusion criteria. Across these studies, we identified common GEWE variables that emerged repeatedly as significant predictors of sector outcomes. We grouped these variables into 10 thematic categories, which we termed 'gender-related levers'. These levers were then classified by the strength of evidence into Wedges, Foundations and Facilitators. Wedges are gender-related levers that had strong associations with improved outcomes across multiple sectors. They include: 'control over income/assets/resources', 'decision-making power' and 'education'. Elements of these levers overlap, but combined, they encapsulate agency. Increasing female agency promotes equality and broadly improves health and development for women, their families and their communities. The second classification, Foundations, displayed strong, positive associations across FP, MNCH and nutrition. Foundations have a more proximal relationship with sector outcomes and include: 'equitable interpersonal relationships', 'mobility' and 'personal safety'. Finally, the third group of levers, Facilitators, was associated with improved outcomes in two to three sectors and include: 'access to information', 'community groups', 'paid labour' and 'rights'. These levers make it easier for women and girls to achieve their goals and are more traditional elements of development programmes. Overall, gender-related levers were associated with improvements in a variety of health and development outcomes. Furthermore, these associations were cross-sectoral, suggesting that to fully realize the benefits of promoting GEWE, the development community must collaborate in co-ordinated and integrated ways across multiple sectors. More research is needed to identify the mechanisms by which gendered interventions work and under what circumstances. © The Author 2016. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
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Qiu, Yanyan; Zhang, Yanan; Li, Jun-Xu
2015-02-15
Although imidazoline I2 receptor ligands have been used as discriminative stimuli, the role of efficacy of I2 receptor ligands as a critical determinant in drug discrimination has not been explored. This study characterized the discriminative stimulus effects of selective imidazoline I2 receptor ligands BU224 (a low-efficacy I2 receptor ligand) and phenyzoline (a higher efficacy I2 receptor ligand) in rats. Two groups of male Sprague-Dawley rats were trained to discriminate 5.6mg/kg BU224 or 32mg/kg phenyzoline (i.p.) from their vehicle in a two-lever food-reinforced drug discrimination procedure, respectively. All rats acquired the discriminations after an average of 18 (BU224) and 56 (phenyzoline) training sessions, respectively. BU224 and phenyzoline completely substituted for one another symmetrically. Several I2 receptor ligands (tracizoline, CR4056, RS45041, and idazoxan) all occasioned>80% drug-associated lever responding in both discriminations. The I2 receptor ligand 2-BFI and a monoamine oxidase inhibitor harmane occasioned>80% drug-associated lever responding in rats discriminating BU224. Other drugs that occasioned partial or less substitution to BU224 cue included clonidine, methamphetamine, ketamine, morphine, methadone and agmatine. Clonidine, methamphetamine and morphine also only produced partial substitution to phenyzoline cue. Naltrexone, dopamine D2 receptor antagonist haloperidol and serotonin (5-HT)2A receptor antagonist MDL100907 failed to alter the discriminative stimulus effects of BU224 or phenyzoline. Combined, these results are the first to demonstrate that BU224 and phenyzoline can serve as discriminative stimuli and that the low-efficacy I2 receptor ligand BU224 shares similar discriminative stimulus effects with higher-efficacy I2 receptor ligands such as phenyzoline and 2-BFI. Copyright © 2015 Elsevier B.V. All rights reserved.
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Effects of baclofen and raclopride on reinstatement of cocaine self-administration in the rat.
Froger-Colléaux, Christelle; Castagné, Vincent
2016-04-15
At present there is no satisfactory treatment against relapse of drug-seeking behavior. Relapse can be modeled in laboratory animals using reinstatement procedures, whereby previously extinguished self-administration for a drug is reinstated by different factors, such as exposure to cues or drug priming. It is thought that activation of gamma-aminobutyric acid (GABA) B receptor complexes could represent a promising approach to pharmacotherapy for diminishing relapse potential with drugs possessing reinforcing properties. The effects of baclofen (a prototypic GABAB receptor agonist) on cue-induced cocaine reinstatement were evaluated in the rat with or without a priming injection of cocaine. The effects of raclopride (an antagonist of dopamine D2 receptors) were also evaluated. Cue-induced reinstatement under vehicle resulted in a significant increase in the number of presses on the active lever, as compared with extinction lever responding. This effect was accentuated in rats receiving a priming injection of cocaine (cocaine-plus-cue-induced reinstatement). Baclofen, at doses without effects on food-motivated operant behavior (2.5 and 5mg/kg i.p.), dose-dependently decreased the number of active lever presses during cue-induced reinstatement. Baclofen had slightly weaker effects on cocaine-plus-cue-induced reinstatement. Raclopride (0.08 and 0.15 mg/kg s.c.) had similar effects against cue-induced reinstatement although it failed to inhibit cocaine-plus-cue-induced reinstatement at the lower dose. Baclofen dose-dependently and selectively decreased reinstatement of cocaine self-administration. The data obtained provide support for the potential anti-craving efficacy of baclofen in the treatment of cocaine drug-seeking. Copyright © 2016 Elsevier B.V. All rights reserved.
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Font, Laura; Mingote, Susana; Farrar, Andrew M.; Pereira, Mariana; Worden, Lila; Stopper, Colin; Port, Russell G.
2009-01-01
Rationale Nucleus accumbens dopamine (DA) participates in the modulation of instrumental behavior, including aspects of behavioral activation and effort-related choice behavior. Rats with impaired accumbens DA transmission reallocate their behavior away from food-reinforced activities that have high response requirements and instead select less-effortful types of food-seeking behavior. Although accumbens DA is considered a critical component of the brain circuitry regulating effort-related processes, emerging evidence also implicates adenosine A2A receptors. Objective The present work was undertaken to test the hypothesis that accumbens A2A receptor stimulation would produce effects similar to those produced by DA depletion or antagonism. Materials and methods Three experiments assessed the effects of the adenosine A2A agonist CGS 21680 on performance of a concurrent choice task (lever pressing for preferred food vs. intake of less preferred chow) that is known to be sensitive to DA antagonists and accumbens DA depletions. Results Systemic injections of CGS 21680 reduced lever pressing but did not increase feeding. In contrast, bilateral infusions of the adenosine A2A receptor agonist CGS 21680 (6.0–24.0 ng) into the nucleus accumbens decreased lever pressing for the preferred food but substantially increased consumption of the less preferred chow. Injections of CGS 21680 into a control site dorsal to the accumbens were ineffective. Conclusions Taken together, these results are consistent with the hypothesis that local stimulation of adenosine A2A receptors in nucleus accumbens produces behavioral effects similar to those induced by accumbens DA depletions. Accumbens adenosine A2A receptors appear to be a component of the brain circuitry regulating effort-related choice behavior. PMID:18491078
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Worden, Lila T; Shahriari, Mona; Farrar, Andrew M; Sink, Kelly S; Hockemeyer, Jörg; Müller, Christa E; Salamone, John D
2009-04-01
Brain dopamine (DA) participates in the modulation of instrumental behavior, including aspects of behavioral activation and effort-related choice behavior. Rats with impaired DA transmission reallocate their behavior away from food-seeking behaviors that have high response requirements, and instead select less effortful alternatives. Although accumbens DA is considered a critical component of the brain circuitry regulating effort-related choice behavior, emerging evidence demonstrates a role for adenosine A(2A) receptors. Adenosine A(2A) receptor antagonism has been shown to reverse the effects of DA antagonism. The present experiments were conducted to determine if this effect was dependent upon the subtype of DA receptor that was antagonized to produce the changes in effort-related choice. The adenosine A(2A) receptor antagonist MSX-3 (0.5-2.0 mg/kg IP) was assessed for its ability to reverse the effects of the D1 family antagonist SCH39166 (ecopipam; 0.2 mg/kg IP) and the D2 family antagonist eticlopride (0.08 mg/kg IP), using a concurrent lever pressing/chow feeding procedure. MSX-3 produced a substantial dose-related reversal of the effects of eticlopride on lever pressing and chow intake. At the highest dose of MSX-3, there was a complete reversal of the effects of eticlopride on lever pressing. In contrast, MSX-3 produced only a minimal attenuation of the effects of SCH39166, as measured by regression and effect size analyses. The greater ability of MSX-3 to reverse the effects of D2 vs. D1 blockade may be related to the colocalization of D2 and adenosine A(2A) receptors on the same population of striatal neurons.
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MacInnes, Nicholas; Handley, Sheila L
2002-01-01
The molecular nature and functions of the I2 subtype of imidazoline binding sites are unknown but evidence suggests an association with monoamine oxidase (MAO). Rats can distinguish the selective imidazoline I2-site ligand 2-BFI from vehicle in drug discrimination, indicating functional consequences of occupation of these sites. We have used drug discrimination to investigate the nature of the discriminable stimulus, especially in relation to MAO inhibition. Following training to distinguish 2-BFI 7 mg kg−1 i.p. from saline vehicle in two-lever operant-chambers, male Hooded Lister rats underwent sessions where test substances were given instead and the proportion of lever presses on the 2-BFI-associated lever (substitution) recorded. 2-BFI; its cogeners BU216, BU224, BU226 and LSL60101; the reversible MAO-A inhibitors moclobemide and RO41-1049; the β-carbolines harmane, norharmane and harmaline which also reversibly inhibit MAO-A, and the anti-addictive substance ibogaine exhibited potent, dose-dependent substitution for 2-BFI. Agmatine, and LSL60125 substituted at one dose only. The reversible MAO-B inhibitors lazabemide and RO16-1649; the σ2-site ligand SKF10,047 and the I2A-site ligand, amiloride, failed to substitute. The irreversible inhibitor of MAO, deprenyl, substituted for 2-BFI while clorgyline did not. These results suggest imidazoline I2 site ligands produce a common discriminable stimulus that appears associated with reversible inhibition of MAO-A rather than MAO-B, possibly through increases in extracellular concentration of one or more monoamines. Ibogaine exhibits a commonality in its subjective effects with those of I2-site ligands. PMID:11877331
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Yankelevitch-Yahav, Roni; Roni, Yankelevitch-Yahav; Joel, Dapha; Daphna, Joel
2013-11-01
In comparison to studies of the involvement of the serotonergic, dopaminergic, and glutamatergic systems in the pathophysiology of obsessive-compulsive disorder (OCD), research on the involvement of the cholinergic system in this disorder has remained sparse. The aim of this study was to test the role of the cholinergic system in compulsive behavior using the signal attenuation rat model of OCD. In this model, "compulsive" behavior is induced by attenuating a signal indicating that a lever-press response was effective in producing food. The acetylcholinesterase inhibitor physostigmine (0.05, 0.10, and 0.15 mg/kg), the nicotinic agonist nicotine (0.03, 0.06, 0.10, 0.30, 0.60, and 1.00 mg/kg), the nicotinic antagonist mecamylamine (1, 3, 5, and 8 mg/kg), the muscarinic agonist oxotremorine (0.0075, 0.0150, and 0.0300 mg/kg), and the muscarinic antagonist scopolamine (0.15, 0.50, 1.00, and 1.50 mg/kg) were acutely administered to rats just before assessing their lever-press responding following signal attenuation (experiments 1, 3, 5, 7, and 9, respectively). Because the effects of signal attenuation are assessed under extinction conditions, drug doses that were effective in the above experiments were also tested in an extinction session of lever-press responding that was not preceded by signal attenuation (experiments 2, 4, 6, 8, and 10). Acute systemic administration of the cholinergic agents did not exert a selective anti- or pro-compulsive effect in the signal attenuation model. Acetylcholine does not seem to play a role in the signal attenuation rat model of OCD.
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MacInnes, Nicholas; Handley, Sheila L
2002-03-01
1. The molecular nature and functions of the I(2) subtype of imidazoline binding sites are unknown but evidence suggests an association with monoamine oxidase (MAO). Rats can distinguish the selective imidazoline I(2)-site ligand 2-BFI from vehicle in drug discrimination, indicating functional consequences of occupation of these sites. We have used drug discrimination to investigate the nature of the discriminable stimulus, especially in relation to MAO inhibition. 2. Following training to distinguish 2-BFI 7 mg kg(-1) i.p. from saline vehicle in two-lever operant-chambers, male Hooded Lister rats underwent sessions where test substances were given instead and the proportion of lever presses on the 2-BFI-associated lever (substitution) recorded. 3. 2-BFI; its cogeners BU216, BU224, BU226 and LSL60101; the reversible MAO-A inhibitors moclobemide and RO41-1049; the beta-carbolines harmane, norharmane and harmaline which also reversibly inhibit MAO-A, and the anti-addictive substance ibogaine exhibited potent, dose-dependent substitution for 2-BFI. 4. Agmatine, and LSL60125 substituted at one dose only. The reversible MAO-B inhibitors lazabemide and RO16-1649; the sigma(2)-site ligand SKF10,047 and the I(2A)-site ligand, amiloride, failed to substitute. The irreversible inhibitor of MAO, deprenyl, substituted for 2-BFI while clorgyline did not. 5. These results suggest imidazoline I(2) site ligands produce a common discriminable stimulus that appears associated with reversible inhibition of MAO-A rather than MAO-B, possibly through increases in extracellular concentration of one or more monoamines. Ibogaine exhibits a commonality in its subjective effects with those of I(2)-site ligands.
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Prosthetic Hand For Holding Rods, Tools, And Handles
NASA Technical Reports Server (NTRS)
Belcher, Jewell G., Jr.; Vest, Thomas W.
1995-01-01
Prosthetic hand with quick-grip/quick-release lever broadens range of specialized functions available to lower-arm amputee by providing improved capabilities for gripping rods, tools, handles, and like. Includes two stationary lower fingers opposed by one pivoting upper finger. Lever operates in conjunction with attached bracket.
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Stratford, Thomas R; Wirtshafter, David
2012-05-01
Previous studies have shown that large increases in food intake in nondeprived animals can be induced by injections of both the GABA(A) agonist muscimol and the μ-opioid agonist DAMGO into the nucleus accumbens shell (AcbSh), while injections of the catecholamine agonist amphetamine have little effect. In the current study we examined whether injections of these drugs are able to increase food-reinforced lever pressing in nondeprived rats. Twelve subjects were trained to lever press on a continuous reinforcement schedule while food deprived and were then tested after being placed back on ad libitum feeding. Under these conditions, responding was markedly increased by injections of either muscimol or DAMGO, although the onset of the effects of the latter drug was delayed by 30-40 min. In contrast, amphetamine injections failed to increase reinforced lever pressing, although they did enhance responding on a non-reinforced lever, presumably reflecting alterations in behavioral activation. These results demonstrate that stimulation of GABA(A) and μ-opioid receptors within the AcbSh is able to promote not only food intake, but also food-directed operant behavior. In contrast, stimulation of AcbSh dopamine receptors may enhance behavioral arousal, but does not appear to specifically potentiate behaviors directed toward food procurement. Copyright © 2012 Elsevier Inc. All rights reserved.
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Ergonomic evaluation of a mechanical anastomotic stapler used by Japanese surgeons.
Kono, Emiko; Tada, Mitsunori; Kouchi, Makiko; Endo, Yui; Tomizawa, Yasuko; Matsuo, Tomoko; Nomura, Sachiyo
2014-06-01
The satisfaction rating of currently available mechanical staplers for Japanese surgeons with small hands is low. To identify the issue, we examined the relationship of hand dimensions and grip force with the operation force of a mechanical circular stapler. Hand dimensions and grip force were measured in 113 Japanese surgeons (52 men and 61 women). We then evaluated the relationship between grip width and the operation force required to push the lever of the stapler, at three points on the lever, using a digital force gauge. The optimal grip width of the dominant hand was 62.5 ± 8.5 mm for men and 55.5 ± 5.9 mm for women (p < 0.001). The maximum grip force of the dominant hand was 44.2 ± 6.1 kg for men and 29.7 ± 4.5 kg for women (p < 0.001) and the maximum operation force required to push the lever 7.0, 45.0, and 73.0 mm from the end of the lever was 21.8, 28.6, and 42.4 kg, respectively. To our knowledge, this is the first ergonomic study of a surgical stapler to be conducted in Asia. Firing the stapler by gripping the proximal side of the lever is physically impossible for most Japanese women surgeons since the required operation force exceeds the maximum grip force, which probably accounts for the stress perceived by these women.
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The Mean as the Balance Point: Thought Experiments with Measuring Sticks
ERIC Educational Resources Information Center
Flores, A.
2008-01-01
This article presents activities to help students establish a connection between the mean and the balance point of a lever. The lever and its law are discussed briefly. Thought experiments with a meterstick are presented to emphasize different properties of the mean and weighted averages. (Contains 16 figures.)
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26. VIEW FROM EAST IN BRIDGE TENDER'S HOUSE, LEVERS FOR ...
26. VIEW FROM EAST IN BRIDGE TENDER'S HOUSE, LEVERS FOR GASOLINE ENGINE OPERATION FOR BRIDGE AND THEIR CONNECTIONS TO CONTROL RODS ON DOWNSTREAM SIDE OF SWING-SPAN; new bridge located in background - Tipers Bridge, Spanning Great Wicomico River at State Route 200, Kilmarnock, Lancaster County, VA
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25. VIEW EAST IN BRIDGE TENDER'S HOUSE, (left) ORIGINAL LEVERS ...
25. VIEW EAST IN BRIDGE TENDER'S HOUSE, (left) ORIGINAL LEVERS FOR GASOLINE ENGINE OPERATION OF SWING-SPAN, (right) PANEL F ELECTRIC OPERATION OF GATES AND SWING-SPAN; new bridge located in background - Tipers Bridge, Spanning Great Wicomico River at State Route 200, Kilmarnock, Lancaster County, VA
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46 CFR 160.035-2 - General requirements for lifeboats.
Code of Federal Regulations, 2011 CFR
2011-10-01
... lever, from the keel to the side bench, shall be painted or otherwise colored white, to provide a contrasting background for the lever. This band of white should be approximately 12 inches wide depending on the internal arrangements of the lifeboat. (d) For the purpose of calculations and conducting tests...
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46 CFR 160.035-2 - General requirements for lifeboats.
Code of Federal Regulations, 2010 CFR
2010-10-01
... lever, from the keel to the side bench, shall be painted or otherwise colored white, to provide a contrasting background for the lever. This band of white should be approximately 12 inches wide depending on the internal arrangements of the lifeboat. (d) For the purpose of calculations and conducting tests...
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The Relationship between State Policy Levers and Student Mobility
ERIC Educational Resources Information Center
Gross, Jacob P. K.; Berry, Matthew S.
2016-01-01
To address conceptual and methodological shortcomings in the extant literature on student mobility, this study employs event history modeling to describe and explain how state policy levers, specifically state grant aid, relates to mobility and baccalaureate degree completion. We find that state grant aid reduces mobility, but less so than…
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García-Fuster, M. Julia; Parsegian, Aram; Watson, Stanley J.; Akil, Huda; Flagel, Shelly B.
2018-01-01
Rationale Environmental challenges during adolescence, such as drug exposure, can cause enduring behavioral and molecular changes that contribute to life-long maladaptive behaviors, including addiction. Selectively bred high-responder (bHR) and low-responder (bLR) rats represent a unique model for assessing the long-term impact of adolescent environmental manipulations, as they inherently differ on a number of addiction-related traits. bHR rats are considered “addiction-prone”, whereas bLR rats are “addiction-resilient”, at least under baseline conditions. Moreover, relative to bLRs, bHR rats are more likely to attribute incentive motivational value to reward cues, or to “sign-track”. Objectives We utilized bHR and bLR rats to determine whether adolescent cocaine exposure can alter their inborn behavioral and neurobiological profiles, with a specific focus on Pavlovian conditioned approach behavior (i.e. sign- vs. goal-tracking) and hippocampal neurogenesis. Methods bHR and bLR rats were administered cocaine (15 mg/kg) or saline for 7 days during adolescence (postnatal day, PND 33–39) and subsequently tested for Pavlovian conditioned approach behavior in adulthood (PND 62–75), wherein an illuminated lever (conditioned stimulus) was followed by the response-independent delivery of a food pellet (unconditioned stimulus). Behaviors directed towards the lever and the food cup were recorded as sign- and goal-tracking, respectively. Hippocampal cell genesis was evaluated on PND 77 by immunohistochemistry. Results Adolescent cocaine exposure impaired hippocampal cell genesis (proliferation and survival) and enhanced the inherent propensity to goal-track in adult bLR, but not bHR, rats. Conclusions Adolescent cocaine exposure elicits long-lasting changes in stimulus-reward learning and enduring deficits in hippocampal neurogenesis selectively in adult bLR rats. PMID:28210781
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Cunningham, Colin S; Moerke, Megan J; Javors, Martin A; Carroll, F Ivy; McMahon, Lance R
2016-12-01
Chronic treatment can differentially impact the effects of pharmacologically related drugs that differ in receptor selectivity and efficacy. The impact of daily nicotine treatment on the effects of nicotinic ACh receptor (nAChR) agonists was examined in two groups of rhesus monkeys discriminating nicotine (1.78 mg·kg -1 base weight) from saline. One group received additional nicotine treatment post-session (1.78 mg·kg -1 administered five times daily, each dose 2 h apart; i.e. Daily group), and the second group did not (Intermittent group). Daily repeated nicotine treatment produced a time-related increase in saliva cotinine. There was no significant difference in the ED 50 values of the nicotine discriminative stimulus between the Daily and Intermittent group. Mecamylamine antagonized the effects of nicotine, whereas dihydro-β-erythroidine did not. Midazolam produced 0% nicotine-lever responding. The nAChR agonists epibatidine, RTI-36, cytisine and varenicline produced >96% nicotine-lever responding in the Intermittent group. The respective maximum effects in the Daily group were 100, 72, 59 and 28%, which shows that the ability of varenicline to produce nicotine-like responding was selectively decreased in the Daily as compared with the Intermittent group. When combined with nicotine, both varenicline and cytisine increased the potency of nicotine to produce discriminative stimulus effects. Nicotine treatment has a greater impact on the sensitivity to the effects of varenicline as compared with some other nAChR agonists. Collectively, these results strongly suggest that varenicline differs from nicotine in its selectivity for multiple nAChR subtypes. © 2016 The British Pharmacological Society.
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Cunningham, Colin S; Moerke, Megan J; Javors, Martin A; Carroll, F Ivy
2016-01-01
Background and Purpose Chronic treatment can differentially impact the effects of pharmacologically related drugs that differ in receptor selectivity and efficacy. Experimental Approach The impact of daily nicotine treatment on the effects of nicotinic ACh receptor (nAChR) agonists was examined in two groups of rhesus monkeys discriminating nicotine (1.78 mg·kg−1 base weight) from saline. One group received additional nicotine treatment post‐session (1.78 mg·kg−1 administered five times daily, each dose 2 h apart; i.e. Daily group), and the second group did not (Intermittent group). Key Results Daily repeated nicotine treatment produced a time‐related increase in saliva cotinine. There was no significant difference in the ED50 values of the nicotine discriminative stimulus between the Daily and Intermittent group. Mecamylamine antagonized the effects of nicotine, whereas dihydro‐β‐erythroidine did not. Midazolam produced 0% nicotine‐lever responding. The nAChR agonists epibatidine, RTI‐36, cytisine and varenicline produced >96% nicotine‐lever responding in the Intermittent group. The respective maximum effects in the Daily group were 100, 72, 59 and 28%, which shows that the ability of varenicline to produce nicotine‐like responding was selectively decreased in the Daily as compared with the Intermittent group. When combined with nicotine, both varenicline and cytisine increased the potency of nicotine to produce discriminative stimulus effects. Conclusion and Implications Nicotine treatment has a greater impact on the sensitivity to the effects of varenicline as compared with some other nAChR agonists. Collectively, these results strongly suggest that varenicline differs from nicotine in its selectivity for multiple nAChR subtypes. PMID:27667659
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Drinking Water Quality Governance: A Comparative Case Study of Brazil, Ecuador, and Malawi.
Kayser, Georgia L; Amjad, Urooj; Dalcanale, Fernanda; Bartram, Jamie; Bentley, Margaret E
2015-04-01
Human health is greatly affected by inadequate access to sufficient and safe drinking water, especially in low and middle-income countries. Drinking water governance improvements may be one way to better drinking water quality. Over the past decade, many projects and international organizations have been dedicated to water governance; however, water governance in the drinking water sector is understudied and how to improve water governance remains unclear. We analyze drinking water governance challenges in three countries-Brazil, Ecuador, and Malawi-as perceived by government, service providers, and civil society organizations. A mixed methods approach was used: a clustering model was used for country selection and qualitative semi-structured interviews were used with direct observation in data collection. The clustering model integrated political, economic, social and environmental variables that impact water sector performance, to group countries. Brazil, Ecuador and Malawi were selected with the model so as to enhance the generalizability of the results. This comparative case study is important because similar challenges are identified in the drinking water sectors of each country; while, the countries represent diverse socio-economic and political contexts, and the selection process provides generalizability to our results. We find that access to safe water could be improved if certain water governance challenges were addressed: coordination and data sharing between ministries that deal with drinking water services; monitoring and enforcement of water quality laws; and sufficient technical capacity to improve administrative and technical management of water services at the local level. From an analysis of our field research, we also developed a conceptual framework that identifies policy levers that could be used to influence governance of drinking water quality on national and sub-national levels, and the relationships between these levers.
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Drinking Water Quality Governance: A Comparative Case Study of Brazil, Ecuador, and Malawi
Kayser, Georgia L.; Amjad, Urooj; Dalcanale, Fernanda; Bartram, Jamie; Bentley, Margaret E.
2015-01-01
Human health is greatly affected by inadequate access to sufficient and safe drinking water, especially in low and middle-income countries. Drinking water governance improvements may be one way to better drinking water quality. Over the past decade, many projects and international organizations have been dedicated to water governance; however, water governance in the drinking water sector is understudied and how to improve water governance remains unclear. We analyze drinking water governance challenges in three countries—Brazil, Ecuador, and Malawi—as perceived by government, service providers, and civil society organizations. A mixed methods approach was used: a clustering model was used for country selection and qualitative semi-structured interviews were used with direct observation in data collection. The clustering model integrated political, economic, social and environmental variables that impact water sector performance, to group countries. Brazil, Ecuador and Malawi were selected with the model so as to enhance the generalizability of the results. This comparative case study is important because similar challenges are identified in the drinking water sectors of each country; while, the countries represent diverse socio-economic and political contexts, and the selection process provides generalizability to our results. We find that access to safe water could be improved if certain water governance challenges were addressed: coordination and data sharing between ministries that deal with drinking water services; monitoring and enforcement of water quality laws; and sufficient technical capacity to improve administrative and technical management of water services at the local level. From an analysis of our field research, we also developed a conceptual framework that identifies policy levers that could be used to influence governance of drinking water quality on national and sub-national levels, and the relationships between these levers. PMID:25798068
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Pierson, W.M.
1958-09-16
A vacuum tank is described for a calutron and the mounting means for the tank whereby the tank mav be convenlently positioned in the proper place between the poles of the magnet and there readily adjuated in height. A plurality of grooved guide wheels are mounted on adjustable levers attached to one side of the tank, along with a plurality of plain rollers mounted on adjuatable levers attached to the same side of the tank on the opposite edge. The grooved guide wheels and rollers cooperate with a guide track and runway, respectively, fer movement of the tank into and out of the magant gap, while the adjustable levers permit the accurate positioning of the tank between the magnet pole pieces.
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Gauthier, Jamie M; Tassin, David H; Dwoskin, Linda P; Kantak, Kathleen M
2014-07-15
Attention Deficit Hyperactivity Disorder (ADHD) is associated with dysfunctional prefrontal and striatal circuitry and dysregulated dopamine neurotransmission. Spontaneously Hypertensive Rats (SHR), a heuristically useful animal model of ADHD, were evaluated against normotensive Wistar (WIS) controls to determine whether dopamine D1 receptor blockade of either prelimbic prefrontal cortex (plPFC) or lateral dorsal striatum (lDST) altered learning functions of both interconnected sites. A strategy set shifting task measured plPFC function (behavioral flexibility/executive function) and a reward devaluation task measured lDST function (habitual responding). Prior to tests, rats received bilateral infusions of SCH 23390 (1.0 μg/side) or vehicle into plPFC or lDST. Following vehicle, SHR exhibited longer lever press reaction times, more trial omissions, and fewer completed trials during the set shift test compared to WIS, indicating slower decision-making and attentional/motivational impairment in SHR. After reward devaluation, vehicle-treated SHR responded less than WIS, indicating relatively less habitual responding in SHR. After SCH 23390 infusions into plPFC, WIS expressed the same behavioral phenotype as vehicle-treated SHR during set shift and reward devaluation tests. In SHR, SCH 23390 infusions into plPFC exacerbated behavioral deficits in the set shift test and maintained the lower rate of responding in the reward devaluation test. SCH 23390 infusions into lDST did not modify set shifting in either strain, but produced lower rates of responding than vehicle infusions after reward devaluation in WIS. This research provides pharmacological evidence for unidirectional interactions between prefrontal and striatal brain regions, which has implications for the neurological basis of ADHD and its treatment. Copyright © 2014 Elsevier B.V. All rights reserved.
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78 FR 57047 - Airworthiness Directives; Eurocopter France Helicopters
Federal Register 2010, 2011, 2012, 2013, 2014
2013-09-17
... (Eurocopter) Model AS350 and AS355 helicopters, to require inspecting for a crack in the control lever... casting of TGB casing assemblies, which may lead to cracking. A crack in the control lever attachment yokes could cause a loss of tail rotor pitch control, and consequently, loss of control of the...
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Measuring How Muscles Function in Levers.
ERIC Educational Resources Information Center
DeMont, M. Edwin
1996-01-01
Presents an exercise that examines the lever systems that function in the chelae of the American lobster. Involves calculating the mechanical and distance advantages of the crusher and pincer chelae and estimating the actual forces generated by the contraction of the muscles and the magnitude of the forces transmitted around the fulcrum to the tip…
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ERIC Educational Resources Information Center
Stecher, Brian M.; Garet, Michael S.; Hamilton, Laura S.; Steiner, Elizabeth D.; Robyn, Abby; Poirier, Jeffrey; Holtzman, Deborah; Fulbeck, Eleanor S.; Chambers, Jay; de los Reyes, Iliana Brodziak
2016-01-01
This document provides the final two appendixes for "Improving Teaching Effectiveness: Implementation. The Intensive Partnerships for Effective Teaching through 2013-2014" (ED580306). Appendix D provides detailed discussions of lever implementation for each site along with the detailed coded lever tables. Appendix E summarizes the…
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46 CFR 56.20-9 - Valve construction.
Code of Federal Regulations, 2011 CFR
2011-10-01
...) motion of the handwheel or operating lever as seen by one facing the end of the valve stem. Each gate, globe, and angle valve must generally be of the rising-stem type, preferably with the stem threads... nonrising-stem valve will be acceptable. Each nonrising-stem valve, lever-operated valve, or other valve...
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46 CFR 56.20-9 - Valve construction.
Code of Federal Regulations, 2013 CFR
2013-10-01
...) motion of the handwheel or operating lever as seen by one facing the end of the valve stem. Each gate, globe, and angle valve must generally be of the rising-stem type, preferably with the stem threads... nonrising-stem valve will be acceptable. Each nonrising-stem valve, lever-operated valve, or other valve...
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46 CFR 56.20-9 - Valve construction.
Code of Federal Regulations, 2012 CFR
2012-10-01
...) motion of the handwheel or operating lever as seen by one facing the end of the valve stem. Each gate, globe, and angle valve must generally be of the rising-stem type, preferably with the stem threads... nonrising-stem valve will be acceptable. Each nonrising-stem valve, lever-operated valve, or other valve...
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46 CFR 56.20-9 - Valve construction.
Code of Federal Regulations, 2014 CFR
2014-10-01
...) motion of the handwheel or operating lever as seen by one facing the end of the valve stem. Each gate, globe, and angle valve must generally be of the rising-stem type, preferably with the stem threads... nonrising-stem valve will be acceptable. Each nonrising-stem valve, lever-operated valve, or other valve...
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46 CFR 58.25-70 - Steering-gear control systems.
Code of Federal Regulations, 2013 CFR
2013-10-01
... MACHINERY AND RELATED SYSTEMS Steering Gear § 58.25-70 Steering-gear control systems. (a) Each power-driven... arranged so that one operation of the switch's lever automatically supplies power to a complete system and its associated power unit or units. This switch must be— (1) Operated by one lever; (2) Arranged so...
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46 CFR 58.25-70 - Steering-gear control systems.
Code of Federal Regulations, 2014 CFR
2014-10-01
... MACHINERY AND RELATED SYSTEMS Steering Gear § 58.25-70 Steering-gear control systems. (a) Each power-driven... arranged so that one operation of the switch's lever automatically supplies power to a complete system and its associated power unit or units. This switch must be— (1) Operated by one lever; (2) Arranged so...
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NASA Technical Reports Server (NTRS)
Autrey, David (Inventor); Morrison, Terrell Lee (Inventor); Kaufman, Cory (Inventor)
2017-01-01
A toilet for use on a space vehicle has a toilet bowl having a storage canister at a remote end for receiving human waste. The compactor includes a cable connected to a lever which pulls the cable in a direction forcing the compactor into the storage canister to compact the captured waste when the lever is actuated.
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29 CFR 1918.52 - Specific requirements.
Code of Federal Regulations, 2011 CFR
2011-07-01
... to join sections of, preventer guys. (b) Stoppers. (1) Chain topping lift stoppers shall be in good... chain. (2) Chain stoppers shall be shackled or otherwise secured so that their links are not bent by... control lever is pulled back and lowers when the lever is pushed forward. (d) Heel blocks. (1) When an...
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29 CFR 1918.52 - Specific requirements.
Code of Federal Regulations, 2014 CFR
2014-07-01
... to join sections of, preventer guys. (b) Stoppers. (1) Chain topping lift stoppers shall be in good... chain. (2) Chain stoppers shall be shackled or otherwise secured so that their links are not bent by... control lever is pulled back and lowers when the lever is pushed forward. (d) Heel blocks. (1) When an...
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29 CFR 1918.52 - Specific requirements.
Code of Federal Regulations, 2010 CFR
2010-07-01
... to join sections of, preventer guys. (b) Stoppers. (1) Chain topping lift stoppers shall be in good... chain. (2) Chain stoppers shall be shackled or otherwise secured so that their links are not bent by... control lever is pulled back and lowers when the lever is pushed forward. (d) Heel blocks. (1) When an...
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29 CFR 1918.52 - Specific requirements.
Code of Federal Regulations, 2013 CFR
2013-07-01
... to join sections of, preventer guys. (b) Stoppers. (1) Chain topping lift stoppers shall be in good... chain. (2) Chain stoppers shall be shackled or otherwise secured so that their links are not bent by... control lever is pulled back and lowers when the lever is pushed forward. (d) Heel blocks. (1) When an...
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29 CFR 1918.52 - Specific requirements.
Code of Federal Regulations, 2012 CFR
2012-07-01
... to join sections of, preventer guys. (b) Stoppers. (1) Chain topping lift stoppers shall be in good... chain. (2) Chain stoppers shall be shackled or otherwise secured so that their links are not bent by... control lever is pulled back and lowers when the lever is pushed forward. (d) Heel blocks. (1) When an...
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Belke, Terry W; Pierce, W David; Jensen, K
2004-07-30
A biobehavioural analysis of activity anorexia suggests that the motivation for physical activity is regulated by food supply and body weight. In the present experiment, food allocation was varied within subjects by prefeeding food-deprived rats 0, 5, 10 and 15 g of food before sessions of lever pressing for wheel-running reinforcement. The experiment assessed the effects of prefeeding on rates of wheel running, lever pressing, and postreinforcement pausing. Results showed that prefeeding animals 5 g of food had no effect. Prefeeding 10 g of food reduced lever pressing for wheel running and rates of wheel running without a significant change in body weight; the effect was, however, transitory. Prefeeding 15 g of food increased the animals' body weights, resulting in a sustained decrease of wheel running and lever pressing, and an increase in postreinforcement pausing. Overall the results indicate that the motivation for physical activity is regulated by changes in local food supply, but is sustained only when there is a concomitant change in body weight.
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Swinford-Jackson, S E; Anastasio, N C; Fox, R G; Stutz, S J; Cunningham, K A
2016-06-02
Intensification of craving elicited by drug-associated cues during abstinence occurs over time in human cocaine users while elevation of cue reactivity ("incubation") is observed in rats exposed to extended forced abstinence from cocaine self-administration. Incubation in rodents has been linked to time-dependent neuronal plasticity in the medial prefrontal cortex (mPFC). We tested the hypothesis that incubation of cue reactivity during abstinence from cocaine self-administration is accompanied by lower potency and/or efficacy of the selective serotonin (5-HT) 5-HT2C receptor (5-HT2CR) agonist WAY163909 to suppress cue reactivity and a shift in the subcellular localization profile of the mPFC 5-HT2CR protein. We observed incubation of cue reactivity (measured as lever presses reinforced by the discrete cue complex) between Day 1 and Day 30 of forced abstinence from cocaine relative to sucrose self-administration. Pharmacological and biochemical analyses revealed that the potency of the selective 5-HT2CR agonist WAY163909 to suppress cue reactivity, the expression of synaptosomal 5-HT2CR protein in the mPFC, and the membrane to cytoplasmic expression of the 5-HT2CR in mPFC were lower on Day 30 vs. Day 1 of forced abstinence from cocaine self-administration. Incubation of cue reactivity assessed during forced abstinence from sucrose self-administration did not associate with 5-HT2CR protein expression in the mPFC. Collectively, these outcomes are the first indication that neuroadaptations in the 5-HT2CR system may contribute to incubation of cocaine cue reactivity. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.
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Swinford-Jackson, Sarah E.; Anastasio, Noelle C.; Fox, Robert G.; Stutz, Sonja J.; Cunningham, Kathryn A.
2016-01-01
Intensification of craving elicited by drug-associated cues during abstinence occurs over time in human cocaine users while elevation of cue reactivity (“incubation”) is observed in rats exposed to extended forced abstinence from cocaine self-administration. Incubation in rodents has been linked to time-dependent neuronal plasticity in the medial prefrontal cortex (mPFC). We tested the hypothesis that incubation of cue reactivity during abstinence from cocaine self-administration is accompanied by lower potency and/or efficacy of the selective 5-HT2CR agonist WAY163909 to suppress cue reactivity and a shift in the subcellular localization profile of the mPFC 5-HT2CR protein. We observed incubation of cue reactivity (measured as lever presses reinforced by the discrete cue complex) between Day 1 and Day 30 of forced abstinence from cocaine relative to sucrose self-administration. Pharmacological and biochemical analyses revealed that the potency of the selective 5-HT2CR agonist WAY163909 to suppress cue reactivity, the expression of synaptosomal 5-HT2CR protein in the mPFC, and the membrane to cytoplasmic expression of the 5-HT2CR in mPFC were lower on Day 30 vs. Day 1 of forced abstinence from cocaine self-administration. Incubation of cue reactivity assessed during forced abstinence from sucrose self-administration did not associate with 5-HT2CR protein expression in the mPFC. Collectively, these outcomes are the first indication that neuroadaptations in the 5-HT2CR system may contribute to incubation of cocaine cue reactivity. PMID:26926963
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Shin, Andrew C.; Townsend, R. Leigh; Patterson, Laurel M.
2011-01-01
Cross-sectional studies in both humans and animals have demonstrated associations between obesity and altered reward functions at the behavioral and neural level, but it is unclear whether these alterations are cause or consequence of the obese state. Reward behaviors were quantified in male, outbred Sprague-Dawley (SD) and selected line obesity-prone (OP) and obesity-resistant (OR) rats after induction of obesity by high-fat diet feeding and after subsequent loss of excess body weight by chronic calorie restriction. As measured by the brief access lick and taste-reactivity paradigms, both obese SD and OP rats “liked” low concentrations of sucrose and corn oil less, but “liked” the highest concentrations more, compared with lean rats, and this effect was fully reversed by weight loss in SD rats. Acute food deprivation was unable to change decreased responsiveness to low concentrations but eliminated increased responsiveness to high concentrations in obese SD rats, and leptin administration in weight-reduced SD rats shifted concentration-response curves toward that seen in the obese state in the brief access lick test. “Wanting” and reinforcement learning as assessed in the incentive runway and progressive ratio lever-pressing paradigms was paradoxically decreased in both obese (compared with lean SD rats) and OP (compared with OR rats). Thus, reversible, obesity-associated, reduced “liking” and “wanting” of low-calorie foods in SD rats suggest a role for secondary effects of the obese state on reward functions, while similar differences between select lines of OP and OR rats before induction of obesity indicate a genetic component. PMID:21849633
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Jentsch, James David; Woods, Jason A; Groman, Stephanie M; Seu, Emanuele
2010-07-01
The tendency for some individuals to partake in high-risk behaviors (eg, substance abuse, gambling, risky sexual activities) is a matter of great public health concern, yet the characteristics and neural bases of this vulnerability are largely unknown. Recent work shows that this susceptibility can be partially predicted by laboratory measures of reward seeking under risk, including the Balloon Analog Risk Task. Rats were trained to respond on two levers: one of which (the 'add lever') increased the size of a potential food reward and a second (the 'cash-out lever') that led to delivery of accrued reward. Crucially, each add-lever response was also associated with a risk that the trial would fail and no reward would be delivered. The relative probabilities that each add-lever press would lead to an addition food pellet or to trial failure (risk) were orthogonally varied. Rats exhibited a pattern of responding characteristic of incentive motivation and risk aversion, with a subset of rats showing traits of high-risk taking and/or suboptimal responding. Neural inactivation studies suggest that the orbitofrontal cortex supports greater reward seeking in the presence or absence of risk, whereas the medial prefrontal cortex is required for optimization of patterns of responding. These findings provide new information about the neural circuitry of decision making under risk and reveal new insights into the biological determinants of risk-taking behaviors that may be useful in developing biomarkers of vulnerability.
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NASA Technical Reports Server (NTRS)
Wesselski, Clarence J. (Inventor); Nagy, Kornel (Inventor)
1992-01-01
A latching device is disclosed which is lever operated sequentially to actuate a set of collet fingers to provide a radial expansion and to actuate a force mechanism to provide a compressive gripping force for attaching first and second devices to one another. The latching device includes a body member having elongated collet fingers which, in a deactuated condition, is insertable through bores on the first and second devices so that gripping terminal portions on the collet fingers are proximate to the end of the bore of the first device while a spring assembly on the body member is located proximate to the outer surface of a second device. A lever is rotatable through 90 deg to move a latching rod to sequentially actuate and expand collet fingers and to actuate the spring assembly by compressing it. During the first 30 deg of movement of the lever, the collet fingers are actuated by the latching rod to provide a radial expansion and during the last 60 deg of movement of the lever, the spring assembly acts as a force mechanism and is actuated to develop a compressive latching force on the devices. The latching rod and lever are connected by a camming mechanism. The amount of spring force in the spring assembly can be adjusted; the body member can be permanently attached by a telescoping assembly to one of the devices; and the structure can be used as a pulling device for removing annular bearings or the like from blind bores.
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Tomie, A; Aguado, A S; Pohorecky, L A; Benjamin, D
2000-03-01
Pavlovian autoshaping CRs are directed and reflexive consummatory responses targeted at objects repeatedly paired with rewarding substances. To evaluate the hypothesis that autoshaping may provide an animal learning model of vulnerability to drug abuse, this study relates individual differences in lever-press autoshaping CR performance in rats to stress-induced corticosterone release and tissue monoamine levels in the mesolimbic dopamine tract. Long-Evans rats (n = 14) were given 20 sessions of Pavlovian autoshaping training wherein the insertion of a retractable lever CS was followed by the response-independent presentation of food US. Large between-subjects differences in lever-press autoshaping CR performance were observed, with group high CR frequency (n = 5) performing many more lever press CRs than group low CR frequency (n = 9). Tail-blood samples were obtained before and after the 20th autoshaping session, then 24 h later the rats were sacrificed and dissection yielded tissue samples of nucleus accumbens (NAC), prefrontal cortex (PFC), caudate putamen (CP), and ventral tegmental area (VTA). Serum levels of postsession corticosterone were elevated in group high CR frequency. HPLC revealed that group high CR frequency had higher tissue levels of dopamine and DOPAC in NAC, lower levels of DOPAC/DA turnover in CP, and lower levels of 5-HIAA and lower 5-HIAA/5-HT turnover in VTA. The neurochemical profile of rats that perform more autoshaping CRs share some features of vulnerability to drug abuse.
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Maccioni, Paola; Zaru, Alessandro; Loi, Barbara; Lobina, Carla; Carai, Mauro A.M.; Gessa, Gian Luigi; Capra, Alessandro; Mugnaini, Claudia; Pasquini, Serena; Corelli, Federico; Hyytiä, Petri; Lumeng, Lawrence; Colombo, Giancarlo
2012-01-01
Background Administration of the GABAB receptor agonist, baclofen, and positive allosteric modulator (PAM), GS39783, has been repeatedly reported to suppress multiple alcohol-related behaviors, including operant oral alcohol self-administration, in rats. The present study was designed to compare the effect of baclofen and GS39783 on alcohol self-administration in three lines of selectively bred, alcohol-preferring rats: Indiana alcohol-preferring (P), Sardinian alcohol-preferring (sP), and Alko Alcohol (AA). Methods Rats of each line were initially trained to respond on a lever, on a fixed ratio (FR) 4 (FR4) schedule of reinforcement, to orally self-administer alcohol (15%, v/v) in daily 30-min sessions. Once responding reached stable levels, rats were exposed to a sequence of experiments testing baclofen (0, 1, 1.7, and 3 mg/kg; i.p.) and GS39783 (0, 25, 50, and 100 mg/kg; i.g.) on FR4 and progressive ratio (PR) schedules of reinforcement. Finally, to assess the specificity of baclofen and GS39783 action, rats were slightly food-deprived and trained to lever-respond for food pellets. Results The rank of order of the reinforcing and motivational properties of alcohol was: P>sP>AA rats. Under both FR and PR schedules of reinforcement, the rank of order of potency and efficacy of baclofen and GS39783 in suppressing alcohol self-administration was: P>sP>AA rats. Only the highest dose of baclofen reduced lever-responding for food pellets; this effect was common to all three rat lines. Conversely, no dose of GS39783 altered lever-responding for food in any rat line. Conclusions These results suggest that: (a) the strength of the reinforcing and motivational properties of alcohol differ among P, sP, and AA rats; (b) the reinforcing and motivational properties of alcohol in P, sP, and AA rats are differentially sensitive to treatment with baclofen and GS39783; (c) the heterogeneity in sensitivity to baclofen and GS39783 of alcohol self-administration in P, sP, and AA rats may resemble the differential effectiveness of pharmacotherapies among the different typologies of human alcoholics; (d) the GABAB receptor is part of the neural substrate mediating the reinforcing and motivational properties of alcohol. PMID:22486245
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Mixed-Mode Bending Method for Delamination Testing
NASA Technical Reports Server (NTRS)
Reeder, James R.; Crews, John R., Jr.
1990-01-01
A mixed mode delamination test procedure was developed combining double cantilever beam (DCB) mode I loading and end-notch fixture (ENF) mode II loading on a split unidirectional laminate. By loading with a lever, a single applied load simultaneously produces mode I and mode II bending loads on the specimen. This mixed-mode bending (MMB) test was analyzed using both finite-element procedures and beam theory to calculate the mode I and mode II components of strain-energy release rate G(sub I) and G(sub II), respectively. A wide range of G(sub I)/G(sub II) ratios can be produced by varying the load position on the lever. As the delamination extended, the G(sub I)/G(sub II) ratios varied by less than 5%. Beam theory equations agreed closely with the finite-element results and provide a basis for selection of G(sub I)/G(sub II) test ratios and a basis for computing the mode I and mode II components of measured delamination toughness. The MMB test was demonstrated using AS4/PEEK (APC2) unidirectional laminates. The MMB test introduced in this paper is rather simple and is believed to offer several advantages over most current mixed-mode test.
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Comparison of cranial form and function in association with diet in natricine snakes.
Hampton, Paul M
2011-12-01
The skull of squamates has many functions, with food acquisition and ingestion being paramount. Snakes vary interspecifically in the frequency, size, and types of prey that are consumed. Natural selection should favor phenotypes that minimize the costs of energy acquisition; therefore, trophic morphology should reflect a snake's primary prey type to enhance some aspect of feeding performance. I measured 19 cranial variables for six natricine species that vary in the frequency with which they consume frogs and fish. Both conventional and phylogenetically corrected analyses indicated that fish-eating snakes have relatively longer upper and lower jaw elements than frog-eating snakes, which tended to have broader skull components. I also compared the ratio of the in-lever to the out-lever lengths of the jaw-closing mechanism [jaw mechanical advantage (MA)] among species. Fish-eating snakes had significantly lower MAs in the jaws than did the frog-eating snakes. This result suggests that piscivores have faster closing jaws and that the jaws of frog-eating snakes have higher closing forces. Cranial morphology and the functional demands of prey capture and ingestion appear to be associated with primary prey type in natricine snakes. Copyright © 2011 Wiley-Liss, Inc.
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1.5 °C ? - Solutions for avoiding catastrophic climate change in this century
NASA Astrophysics Data System (ADS)
Xu, Y.
2017-12-01
The historic Paris Agreement calls for limiting global temperature rise to "well below 2 °C." Because of uncertainties in emission scenarios, climate, and carbon cycle feedback, we interpret the Paris Agreement in terms of three climate risk categories and bring in considerations of low-probability (5%) high impact (LPHI) warming in addition to the central (˜50% probability) value. The current risk category of dangerous warming is extended to more categories, which are defined by us here as follows: >1.5 °C as dangerous; >3 °C as catastrophic; and >5 °C as unknown, implying beyond catastrophic, including existential threats. With unchecked emissions, the central warming can reach the dangerous level within three decades, with the LPHI warming becoming catastrophic by 2050. We outline a three-lever strategy to limit the central warming below the dangerous level and the LPHI below the catastrophic level, both in the near term (<2050) and in the long term (2100): the carbon neutral (CN) lever to achieve zero net emissions of CO2, the super pollutant (SP) lever to mitigate short-lived climate pollutants, and the carbon extraction and sequestration (CES) lever to thin the atmospheric CO2 blanket. Pulling on both CN and SP levers and bending the emissions curve by 2020 can keep the central warming below dangerous levels. To limit the LPHI warming below dangerous levels, the CES lever must be pulled as well to extract as much as 1 trillion tons of CO2 before 2100 to both limit the preindustrial to 2100 cumulative net CO2 emissions to 2.2 trillion tons and bend the warming curve to a cooling trend. In addition to present the analysis above, I will also share (1) perspective on developed and developing world actions and interactions on climate solutions; (2) Prof V. Ramanathan's interactions with the Pontifical Academy of Sciences and other religious groups which are highly valuable to the interdisciplinary audience.
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THE DIAGNOSTIC ACCURACY OF THE LEVER SIGN FOR DETECTING ANTERIOR CRUCIATE LIGAMENT INJURY
Anderson, Amanda; Watson, Seth; Dimeff, Robert J.
2017-01-01
Background An alternative physical examination procedure for evaluating the integrity of the anterior cruciate ligament (ACL) has been proposed in the literature but has not been validated in a broad population of patients with a symptomatic complaint of knee pain for its diagnostic value. Purpose To investigate the diagnostic accuracy of the Lever Sign to detect ACL tears and compare the results to Lachman testing in both supine and prone positions. Study design Prospective, blinded, diagnostic accuracy study. Methods Sixty-two consecutive patients with a complaint of knee pain were independently evaluated for the status of the ACL's integrity with the Lever Sign and the Lachman test in a prone and supine by a blinded examiner before any other diagnostic assessments were completed. Results Twenty-four of the 60 patients included in the analysis had a torn ACL resulting in a prevalence of 40%. The sensitivity of the Lever Sign, prone, and supine Lachman tests were 38, 83, and 67 % respectively and the specificity was 72, 89, and 97% resulting in positive likelihood ratios of 1.4, 7.5, and 24 and negative likelihood ratios of 0.86, 0.19, and 0.34 respectively. The positive predictive values were 47, 83, and 94% and the negative predictive values were 63, 89, and 81% respectively. The diagnostic odds ratios were 1.6, 40, and 70 with a number needed to diagnose of 10.3, 1.4, and 1.6 respectively. Conclusions The results of this study suggest that Lever Sign, in isolation, does not accurately detect the status of the ACL. During the clinical examination, the Lever Sign should be used as an adjunct to the gold standard assessment technique of anterior tibial translation assessment as employed in the Lachman tests in either prone or supine position. Level of Evidence 2 PMID:29234557
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Anker, Justin J; Carroll, Marilyn E
2011-10-01
Environmental factors such as early drug exposure influence drug abuse vulnerability, and evidence also suggests that drug abuse is highly heritable. The purpose of the present study was to determine whether environmental and genetic factors interact to produce additive drug abuse vulnerability. An animal model of relapse was used to examine the effects of adolescent nicotine exposure on adult cocaine seeking in rats bred for high (HiS) and low (LoS) saccharin intake. Rats from HiS and LoS progenitor lines received s.c. injections of nicotine for 10 days (postnatal days 22-31). Rats were then allowed to reach adulthood and were trained to lever press for cocaine infusions. During each self-administration session, the house light (HL) was illuminated and each lever press activated a set of lights adjacent to the lever (LL). Following cocaine self-administration, the HL and LL were deactivated, cocaine solutions were replaced with saline, and rats extinguished lever pressing. Subsequently, rats were tested under a multi-component reinstatement procedure consisting of: (1) cue-induced reinstatement with LL alone and the HL presented alone, (2) cocaine-induced reinstatement without LL and HL present, (3) and cocaine-induced reinstatement with LL present. The results indicated that adolescent nicotine exposure sensitized the reinstatement of cocaine seeking during adulthood in HiS (but not LoS) rats when lever pressing resulted in LL cue presentations. In addition, following administration of the cocaine priming injection, rats exposed to nicotine (vs. saline) during adolescence (LoS and HiS) engaged in more cocaine seeking under the cocaine-primed reinstatement condition when lever pressing illuminated the LL. These results suggest that drug abuse vulnerability may be a function of early life exposure to drugs of abuse in addition to genetic influences. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.
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Tomie, Arthur; Di Poce, Jason; Aguado, Allison; Janes, Amy; Benjamin, Daniel; Pohorecky, Larissa
2003-06-13
Effects of experience with Pavlovian autoshaping procedures on lever-press autoshaping conditioned response (CR) performance and 3H-8-OH-DPAT-labeled binding of 5-HT(1a) receptors as well as 125I-LSD-labeled binding of 5-HT(2a) receptors were evaluated in four groups of male Long-Evans hooded rats. Two groups of rats (Group Paired High CR and Group Paired Low CR) received Pavlovian autoshaping procedures wherein the presentation of a lever (conditioned stimulus, CS) was followed by the response-independent presentation of food (unconditioned stimulus, US). Rats in Group Paired High CR (n=12) showed more rapid CR acquisition and higher asymptotic levels of lever-press autoshaping CR performance relative to rats in Group Low CR (n=12). Group Omission (n=9) received autoshaping with an omission contingency, such that performing the lever-press autoshaping CR resulted in the cancellation the food US, while Group Random (n=9) received presentations of lever CS and food US randomly with respect to one another. Though Groups Omission and Random did not differ in lever-press autoshaping CR performance, Group Omission showed significantly lower levels of 3H-8-OH-DPAT-labeled 5-HT(1a) binding in post-synaptic areas (frontal cortex, septum, caudate putamen), as well as significantly higher plasma corticosterone levels than Group Random. In addition, Group Random showed higher levels of 3H-8-OH-DPAT-labeled 5-HT(1a) binding in pre-synaptic somatodendritic autoreceptors on dorsal raphe nucleus relative to each of the other three groups. Autoradiographic analysis of 125I-LSD-labeled 5-HT(2a) receptor binding revealed no significant differences between Groups Paired High CR and Paired Low CR or between Groups Omission and Random in any brain regions.
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1991-12-03
BANKING Hidden Financial Distribution [CAIMAO JINGJI No8] .................................... .. . .. .. 25 Guangxi Tax Chief on Using Tax Levers [GUANGXI...assets is confused. economy. They are of major importance in the invigo- Under the financial contracting system, the conflict ration of large and...to various economic levers and legal strictures state, and to change enterprises from appendages of the such as financial , fiscal, and tax policies
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Observing Responses and Serial Stimuli: Searching for the Reinforcing Properties of the S-
ERIC Educational Resources Information Center
Escobar, Rogelio; Bruner, Carlos A.
2009-01-01
The control exerted by a stimulus associated with an extinction component (S-) on observing responses was determined as a function of its temporal relation with the onset of the reinforcement component (S+). Lever pressing by rats was reinforced on a mixed random-interval extinction schedule. Each press on a second lever produced stimuli…
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Cognitive Effects on the Child's Internalization of Altruistic Behavior.
ERIC Educational Resources Information Center
Baxter, George W.
Cognitive effects in children's learning of altruistic behavior were tested with an adaptation of Aronfreed's test design and machine. Children in grades 1-4 were presented with a machine with 2 levers. One lever, when pressed, released bubble gum, and the other turned on a light. For two of the three groups the experimenter exclaimed delightedly…
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ERIC Educational Resources Information Center
Hesser, Kathi; Buck, Gayle; Dopp, Sandra
2005-01-01
In the activity described in this article, students will explore how variables in a first-class lever, specifically arm length, position of the fulcrum, and placement of the load, affect the effort needed to lift the load. To begin the lesson, demonstrate to the class how a first-class lever works and review what is meant by the terms fulcrum,…
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Federal Register 2010, 2011, 2012, 2013, 2014
2010-05-17
... commanding the landing gear lever to down the three green landing gear positioning indication was displayed... unsafe condition for the specified products. The MCAI states: It was reported that after commanding the...: It was reported that after commanding the landing gear lever to down the three green landing gear...
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Thorn, David A; Li, Jiuzhou; Qiu, Yanyan; Li, Jun-Xu
2016-09-01
Methamphetamine abuse remains an alarming public heath challenge, with no approved pharmacotherapies available. Agmatine is a naturally occurring cationic polyamine that has previously been shown to attenuate the rewarding and psychomotor-sensitizing effects of methamphetamine. This study examined the effects of agmatine on the discriminative stimulus and hyperthermic effects of methamphetamine. Adult male rats were trained to discriminate 0.32 mg/kg methamphetamine from saline. Methamphetamine dose dependently increased drug-associated lever responding. The nonselective dopamine receptor antagonist haloperidol (0.1 mg/kg) significantly attenuated the discriminative stimulus effects of methamphetamine (5.9-fold rightward shift). Agmatine (10-100 mg/kg) did not substitute for methamphetamine, but significantly attenuated the stimulus effects of methamphetamine, leading to a maximum of a 3.5-fold rightward shift. Acute 10 mg/kg methamphetamine increased the rectal temperature by a maximum of 1.96±0.17°C. Agmatine (10-32 mg/kg) pretreatment significantly attenuated the hyperthermic effect of methamphetamine. Agmatine (10 mg/kg) also significantly reversed methamphetamine-induced temperature increase. Together, these results support further exploration of the value that agmatine may have for the treatment of methamphetamine abuse and overdose.
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Thorn, David A.; Li, Jiuzhou; Qiu, Yanyan; Li, Jun-Xu
2016-01-01
Methamphetamine abuse remains an alarming public heath challenge with no approved pharmacotherapies available. Agmatine is a naturally-occurring cationic polyamine that has previously been shown to attenuate the rewarding and psychomotor-sensitizing effects of methamphetamine. This study examined the effects of agmatine on the discriminative stimulus and hyperthermic effects of methamphetamine. Adult male rats were trained to discriminate 0.32 mg/kg methamphetamine from saline. Methamphetamine dose-dependently increased drug-associated lever responding. The nonselective dopamine receptor antagonist haloperidol (0.1 mg/kg) significantly attenuated the discriminative stimulus effects of methamphetamine (5.9-fold rightward shift). Agmatine (10 –100 mg/kg) did not substitute for methamphetamine but significantly attenuated the stimulus effects of methamphetamine, leading to a maximum of 3.5-fold rightward shift. Acute 10 mg/kg methamphetamine increased the rectal temperature by a maximum of 1.96 ± 0.17 °C. Agmatine (10 – 32 mg/kg) pretreatment significantly attenuated the hyperthermic effect of methamphetamine. Agmatine (10 mg/kg) also significantly reversed methamphetamine-induced temperature increase. Together, these results support further exploration of the value that agmatine may have for treating methamphetamine abuse and overdose. PMID:27232669
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Enhanced performance of aged rats in contingency degradation and instrumental extinction tasks.
Samson, Rachel D; Venkatesh, Anu; Patel, Dhara H; Lipa, Peter; Barnes, Carol A
2014-04-01
Normal aging in rats affects behavioral performance on a variety of associative learning tasks under Pavlovian conditions. There is little information, however, on whether aging also impacts performance of instrumental tasks. Young (9-12 months) and aged (24-27 months) Fisher 344 rats were trained to press distinct levers associated with either maltodextrin or sucrose. The rats in both age groups increased their lever press frequency at a similar rate, suggesting that the initial acquisition of this instrumental task is not affected by aging. Using a contingency degradation procedure, we then addressed whether aged rats could adapt their behavior to changes in action-outcome contingencies. We found that young and aged rats do adapt, but that a different schedule of reinforcement is necessary to optimize performance in each age group. Finally, we also addressed whether aged rats can extinguish a lever press action as well as young rats, using 2 40-min extinction sessions on consecutive days. While extinction profiles were similar in young and aged rats on the first day of training, aged rats were faster to extinguish their lever presses on the second day, in spite of their performance levels being similar at the beginning of the session. Together these data support the finding that acquisition of instrumental lever press behaviors is preserved in aged rats and suggest that they have a different threshold for switching strategies in response to changes in action-outcome associations. This pattern of result implies that age-related changes in the brain are heterogeneous and widespread across structures.
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Evaluation of Physical Examination Tests for Thumb Basal Joint Osteoarthritis
Model, Zina; Liu, Andrew Y.; Kang, Lana; Wolfe, Scott W.; Burket, Jayme C.; Lee, Steve K.
2016-01-01
Background: We compare the ability of 3 diagnostic tests to reproduce the pain of basilar joint arthritis (BJA): the grind test, the lever test (grasping the first metacarpal just distal to the basal joint and shucking back and forth in radial and ulnar directions), and the metacarpophalangeal extension test. Methods: Sixty-two patients with thumb BJA were enrolled. The 3 tests were performed in a random order on both hands of each patient. Prior to testing, patients reported their typical pain level and subsequently rated their pain after each test on a 0 to 10 scale, also specifying the extent to which the test reproduced their thumb pain (fully, partially, not at all). All patients had radiographs that displayed basal joint arthritis. A test was defined as positive for BJA if pain produced was greater than 0. Sensitivity and specificity for each test were calculated using the patients’ history of pain localized to the basal joint and BJA diagnosis on radiographs as the gold standard. Results: The lever test produced the greatest level of pain and best reproduced the presenting pain. The lever test also had the highest sensitivity, high specificity, and the lowest false-negative rate. The grind test had the lowest sensitivity, highest specificity, and highest false-negative rate. Conclusions: The lever test was the diagnostic test that best reproduced the pain caused by thumb basal joint osteoarthritis. We recommend using the lever physical examination test when evaluating the patient with suspected basal joint osteoarthritis. The often-quoted grind test is of limited diagnostic value. PMID:27418899
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Oinio, Ville; Sundström, Mikko; Bäckström, Pia; Uhari-Väänänen, Johanna; Kiianmaa, Kalervo; Raasmaja, Atso; Piepponen, Petteri
2018-05-01
Comorbidity with gambling disorder (GD) and alcohol use disorder (AUD) is well documented. The purpose of our study was to examine the influence of genetic alcohol drinking tendency on reward-guided decision making behavior of rats and the impact of dopamine releaser D-amphetamine on this behavior. In this study, Alko alcohol (AA) and Wistar rats went through long periods of operant lever pressing training where the task was to choose the profitable of two options. The lever choices were guided by different-sized sucrose rewards (one or three pellets), and the probability of gaining the larger reward was slowly changed to a level where choosing the smaller reward would be the most profitable in the long run. After training, rats were injected (s.c.) with dopamine releaser D-amphetamine (0.3, 1.0 mg/kg) to study the impact of rapid dopamine release on this learned decision making behavior. Administration of D-amphetamine promoted unprofitable decision making of AA rats more robustly when compared to Wistar rats. At the same time, D-amphetamine reduced lever pressing responses. Interestingly, we found that this reduction in lever pressing was significantly greater in Wistar rats than in AA rats and it was not linked to motivation to consume sucrose. Our results indicate that conditioning to the lever pressing in uncertain environments is more pronounced in AA than in Wistar rats and indicate that the reinforcing effects of a gambling-like environment act as a stronger conditioning factor for rats that exhibit a genetic tendency for high alcohol drinking.
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Guy, Elizabeth Glenn; Fletcher, Paul J
2014-06-01
Nicotine enhances approach toward and operant responding for conditioned stimuli (CSs), but the effect of exposure during different phases of Pavlovian incentive learning on these measures remains to be determined. These studies examined the effects of administering nicotine early, late or throughout Pavlovian conditioning trials on discriminated approach behavior, nicotine-enhanced responding for conditioned reinforcement, extinction, and the reinstatement of responding for conditioned reinforcement. We also tested the effect of nicotine on approach to a lever-CS in a Pavlovian autoshaping procedure and for this CS to serve as a conditioned reinforcer. Thirsty rats were exposed to 13 conditioning sessions where a light/tone CS was paired with the delivery of water. Nicotine was administered either prior to the first or last seven sessions, or throughout the entire conditioning procedure. Responding for conditioned reinforcement, extinction, and the reinstatement of responding by the stimulus and nicotine were compared across exposure groups. Separately, the effects of nicotine on conditioned approach toward a lever-CS during autoshaping, and responding for that CS as a conditioned reinforcer, were examined. Nicotine exposure was necessary for nicotine-enhanced responding for conditioned reinforcement and the ability for nicotine and the stimulus to additively reinstate responding on the reinforced lever. Nicotine increased contacts with a lever-CS during autoshaping, and removal of nicotine abolished this effect. Prior nicotine exposure was necessary for nicotine-enhanced responding reinforced by the lever. Enhancements in the motivating properties of CSs by nicotine occur independently from duration and timing effects of nicotine exposure during conditioning.
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Enhanced performance of aged rats in contingency degradation and instrumental extinction tasks
Samson, Rachel D.; Venkatesh, Anu; Patel, Dhara H.; Lipa, Peter; Barnes, Carol A.
2014-01-01
Normal aging in rats affects behavioral performance on a variety of associative learning tasks under Pavlovian conditions. There is little information, however, on whether aging also impacts performance of instrumental tasks. Young (9–12 mo) and aged (24–27 mo) Fisher 344 rats were trained to press distinct levers associated with either maltodextrin or sucrose. The rats in both age groups increased their lever press frequency at a similar rate, suggesting that the initial acquisition of this instrumental task is not affected by aging. Using a contingency degradation procedure, we then addressed whether aged rats could adapt their behavior to changes in action-outcome contingencies. We found that young and aged rats do adapt, but that a different schedule of reinforcement is necessary to optimize performance in each age group. Finally, we also addressed whether aged rats can extinguish a lever press action as well as young rats, using two forty minute extinction sessions on consecutive days. While extinction profiles were similar in young and aged rats on the first day of training, aged rats were faster to extinguish their lever presses on the second day, in spite of their performance levels being similar at the beginning of the session. Together these data support the finding that acquisition of instrumental lever press behaviors is preserved in aged rats, and suggest that they have a different threshold for switching strategies in response to changes in action-outcome associations. This pattern of result implies that age-related changes in the brain are heterogeneous and widespread across structures. PMID:24773433
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A Learning Center on the Lever for Young Children.
ERIC Educational Resources Information Center
Keislar, Evan R.; Luckenbill, Maryann
This document describes a project designed to explore the possibilities of children's learning in mechanics. The principle of the lever, one example of a simple machine, was used in the form of a balance toy. The apparatus was set up as a game in a specially devised learning center. The children made non-verbal predictions as to which way the bar…
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Linking Science with Design and Technology in a Stimulating Approach to Teaching about Levers
ERIC Educational Resources Information Center
Davenport, Carol
2015-01-01
Changes in the National Curriculum for England in 2014 included the introduction of levers, gears, and pulleys into primary science. Although simple mechanisms had been part of the design and technology (DT) curriculum for some time, it was the first time that the science behind the mechanisms had been included at the primary school level. These…
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ERIC Educational Resources Information Center
Blauch, Lloyd E.
1933-01-01
During the past quarter of a century there have been rather continuous and persistent efforts for Federal aid to education. Twenty-one years ago the Congress of the United States enacted the Smith-Lever Agricultural Extension Act, and 3 years later it passed the Smith-Hughes Vocational Education Act. Under the Smith-Lever Act and subsequent…
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Model Tests and Computer Simulations of a 15-Barge Tow for the Upper Mississippi River.
1984-01-01
8217.* Damping lever ’v Static stability lever - S u’ - Mses of ship No Hf ...... ydrodynamic moment component jpUR about z axis (yawing moment) N Neem ...towboat designed to push an integrated oil barge tow. The second series of tests were performed using the "Exxon Nashville" and the Exxon Lake Charles
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Implementing a University E-Learning Strategy: Levers for Change within Academic Schools
ERIC Educational Resources Information Center
Sharpe, Rhona; Benfield, Greg; Francis, Richard
2006-01-01
This paper describes the implementation of an e-learning strategy at a single higher education institution in terms of the levers used to promote effective uptake and ensure sustainable embedding. The focus of this work was at the level of the academic school using a range of change practices including the appointment of school-based learning…
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70. DETAIL OF TRACTION CABLE ENGAGEMENT DEVICE. SMALL, KNOBBED LEVER ...
70. DETAIL OF TRACTION CABLE ENGAGEMENT DEVICE. SMALL, KNOBBED LEVER ON BUCKET HANGER WAS PULLED DOWN BY A CAMEL (FIXED CAM RAIL AT CENTER) AS BUCKET ROLLED PAST IT, CAUSING A CLAMP TO CLOSE AGAINST TRACTION CABLE. A SIMILAR CAMEL (NO LONGER EXTANT) DISENGAGED CLAMP ON RECEIVING SIDE. - Shenandoah-Dives Mill, 135 County Road 2, Silverton, San Juan County, CO
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Assessing the Role of Effort Reduction in the Reinforcing Efficacy of Timeout from Avoidance
ERIC Educational Resources Information Center
Galuska, Chad M.; Mikorski, Jeff; Perone, Michael
2012-01-01
Rats responded on concurrent schedules of shock-postponement or deletion (avoidance) and timeout from avoidance. In Experiment 1, 3 rats' responses on one lever postponed shocks for 20 s and responses on a second lever produced a 1-min timeout according to a variable-interval 45-s schedule. Across conditions, a warning signal (white noise) was…
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49 CFR Appendix A to Part 231 - Schedule of Civil Penalties 1
Code of Federal Regulations, 2010 CFR
2010-10-01
... or Hand Brake Parts Wrong Design 2,500 5,000 114.B2Hand Brake Wheel or Lever Has Insufficient Clearance Around Rim or Handle 2,500 5,000 114.B3Hand Brake Wheel/Lever Clearance Insufficient to Vertical... Improperly Applied 2,500 5,000 146.ANotice or Stencil not Posted on Cabooses with Running Boards Removed 650...
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Sader, John E; Lu, Jianing; Mulvaney, Paul
2014-11-01
Calibration of the optical lever sensitivities of atomic force microscope (AFM) cantilevers is especially important for determining the force in AFM measurements. These sensitivities depend critically on the cantilever mode used and are known to differ for static and dynamic measurements. Here, we calculate the ratio of the dynamic and static sensitivities for several common AFM cantilevers, whose shapes vary considerably, and experimentally verify these results. The dynamic-to-static optical lever sensitivity ratio is found to range from 1.09 to 1.41 for the cantilevers studied - in stark contrast to the constant value of 1.09 used widely in current calibration studies. This analysis shows that accuracy of the thermal noise method for the static spring constant is strongly dependent on cantilever geometry - neglect of these dynamic-to-static factors can induce errors exceeding 100%. We also discuss a simple experimental approach to non-invasively and simultaneously determine the dynamic and static spring constants and optical lever sensitivities of cantilevers of arbitrary shape, which is applicable to all AFM platforms that have the thermal noise method for spring constant calibration.
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Ca2+-Induced Rigidity Change of the Myosin VIIa IQ Motif-Single α Helix Lever Arm Extension.
Li, Jianchao; Chen, Yiyun; Deng, Yisong; Unarta, Ilona Christy; Lu, Qing; Huang, Xuhui; Zhang, Mingjie
2017-04-04
Several unconventional myosins contain a highly charged single α helix (SAH) immediately following the calmodulin (CaM) binding IQ motifs, functioning to extend lever arms of these myosins. How such SAH is connected to the IQ motifs and whether the conformation of the IQ motifs-SAH segments are regulated by Ca 2+ fluctuations are not known. Here, we demonstrate by solving its crystal structure that the predicted SAH of myosin VIIa (Myo7a) forms a stable SAH. The structure of Myo7a IQ5-SAH segment in complex with apo-CaM reveals that the SAH sequence can extend the length of the Myo7a lever arm. Although Ca 2+ -CaM remains bound to IQ5-SAH, the Ca 2+ -induced CaM binding mode change softens the conformation of the IQ5-SAH junction, revealing a Ca 2+ -induced lever arm flexibility change for Myo7a. We further demonstrate that the last IQ motif of several other myosins also binds to both apo- and Ca 2+ -CaM, suggesting a common Ca 2+ -induced conformational regulation mechanism. Copyright © 2017 Elsevier Ltd. All rights reserved.
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Dual Optical Levers for Atomic Force Microscopy
NASA Astrophysics Data System (ADS)
Kawakatsu, Hideki; Bleuler, Hannes; Saito, Takashi; Hiroshi, Kougami
1995-06-01
Development of micro machined cantilever and optical lever detection system has greatly facilitated the operation of atomic force microscopy. However, since the detection system measures only the deflection of the cantilever at one set point where the laser beam is focused, care must be taken in implementing force control or in interpreting the acquired data. In this paper, a dual optical lever detection system is introduced, which has the potential to resolve the deformation of the cantilever with multidegree of freedom and thus detect the position of the tip end point with resolution in the 10 pm order. The detection system proved to be effective in real-time monitoring of the behavior of the tip end point while scanning, and in explaining the scanning direction dependence of the acquired images.
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Chronic Health Outcomes and Prescription Drug Copayments in Medicaid.
Kostova, Deliana; Fox, Jared
2017-05-01
Prescription drug copayments and cost-sharing have been linked to reductions in prescription drug use and expenditures. However, little is known about their effect on specific health outcomes. To evaluate the association between prescription drug copayments and uncontrolled hypertension, uncontrolled hypercholesterolemia, and prescription drug utilization among Medicaid beneficiaries with these conditions. Select adults aged 20-64 from NHANES 1999-2012 in 18 states. Uncontrolled hypertension, uncontrolled hypercholesterolemia, and taking medication for each of these conditions. A differencing regression model was used to evaluate health outcomes among Medicaid beneficiaries in 4 states that introduced copayments during the study period, relative to 2 comparison groups-Medicaid beneficiaries in 14 states unaffected by shifts in copayment policy, and a within-state counterfactual group of low-income adults not on Medicaid, while controlling for individual demographic factors and unobserved state-level characteristics. Although uncontrolled hypertension and hypercholesterolemia declined among all low-income persons during the study period, the trend was less pronounced in Medicaid beneficiaries affected by copayments. After netting out concurrent trends in health outcomes of low-income persons unaffected by Medicaid copayment changes, we estimated that introduction of drug copayments in Medicaid was associated with an average rise in uncontrolled hypertension and uncontrolled hypercholesterolemia of 7.7 and 13.2 percentage points, respectively, and with reduced drug utilization for hypercholesterolemia. As Medicaid programs change in the years following the Affordable Care Act, prescription drug copayments may play a role as a lever for controlling hypertension and hypercholesterolemia at the population level.
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Dynamics of Choice: Relative Rate and Amount Affect Local Preference at Three Different Time Scales
ERIC Educational Resources Information Center
Aparicio, Carlos F.; Baum, William M.
2009-01-01
To examine extended control over local choice, the present study investigated preference in transition as food-rate ratio provided by two levers changed across seven components within daily sessions, and food-amount ratio changed across phases. Phase 1 arranged a food-amount ratio of 4:1 (i.e., the left lever delivered four pellets and the right…
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The Effects of Behavioral History on Response Acquisition with Immediate and Delayed Reinforcement
ERIC Educational Resources Information Center
Snycerski, Susan; Laraway, Sean; Huitema, Bradley E.; Poling, Alan
2004-01-01
Effects of prior exposure to the experimental chamber with levers present or absent and variable-time (VT) 60-s water deliveries arranged during one, five, or no 1-hr sessions were examined in rats during a 6-hr response-acquisition session in which presses on one lever produced water delivery immediately or after a 15-s resetting delay, and…
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The jaw is a second-class lever in Pedetes capensis (Rodentia: Pedetidae)
2017-01-01
The mammalian jaw is often modelled as a third-class lever for the purposes of biomechanical analyses, owing to the position of the resultant muscle force between the jaw joint and the teeth. However, it has been proposed that in some rodents the jaws operate as a second-class lever during distal molar bites, owing to the rostral position of the masticatory musculature. In particular, the infraorbital portion of the zygomatico-mandibularis (IOZM) has been suggested to be of major importance in converting the masticatory system from a third-class to a second-class lever. The presence of the IOZM is diagnostic of the hystricomorph rodents, and is particularly well-developed in Pedetes capensis, the South African springhare. In this study, finite element analysis (FEA) was used to assess the lever mechanics of the springhare masticatory system, and to determine the function of the IOZM. An FE model of the skull of P. capensis was constructed and loaded with all masticatory muscles, and then solved for biting at each tooth in turn. Further load cases were created in which each masticatory muscle was removed in turn. The analyses showed that the mechanical advantage of the springhare jaws was above one at all molar bites and very close to one during the premolar bite. Removing the IOZM or masseter caused a drop in mechanical advantage at all bites, but affected strain patterns and cranial deformation very little. Removing the ZM had only a small effect on mechanical advantage, but produced a substantial reduction in strain and deformation across the skull. It was concluded that the masticatory system of P. capensis acts as a second class lever during bites along almost the entire cheek tooth row. The IOZM is clearly a major contributor to this effect, but the masseter also has a part to play. The benefit of the IOZM is that it adds force without substantially contributing to strain or deformation of the skull. This may help explain why the hystricomorphous morphology has evolved multiple times independently within Rodentia. PMID:28875081
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2016-01-01
Parrotfishes (family Labridae: Scarini) are regarded to have important roles for maintaining the ecosystem balance in coral reefs due to their removal of organic matter and calcic substrates by grazing. The purpose of the present study was to clarify the interspecific differences in grazing ability of five parrotfish species (Chlorurus sordidus, C. bowersi, Scarus rivulatus, S. niger and S. forsteni) in relation to interspecific differences in jaw-lever mechanics and the relative weight of the adductor mandibulae (muscles operating jaw closing). The grazing ability was calculated by using stomach contents (CaCO3 weight/organic matter weight) defined as the grazing ability index (GAI). There were significant interspecific differences in GAI (C. sordidus = C. bowersi > S. rivulatus > S. niger = S. forsteni). Teeth of C. sordidus and C. bowersi were protrusive-shape whereas teeth of S. rivulatus, S. niger and S. forsteni were flat-shape. C. sordidus and C. bowersihave jaw-lever mechanics producing a greater biting force and have a larger weight of adductor mandibulae. S. rivulatus has jaw-lever mechanics producing a greater biting force but a smaller weight of adductor mandibulae that produce an intermediate biting force. In contrast, S. niger and S. forsteni have jaw-lever mechanics producing a lesser biting force and have a smaller weight of adductor mandibulae. Feeding rates and foray size of S. rivulatus, S. niger and S. forsteni were greater than C. sordidus and C. bowersi. The degree in bioerosion (GAI × feeding rate) was the largest for S. rivulatusand the smallest for S. forsteni. The degree in bioerosion for C. sordidus was larger than S. niger whereas relatively equal between C. bowersi and S. niger. These results suggest that interspecific difference in GAI was explained by interspecific differences in teeth shape, jaw-lever mechanics and relative weight of adductor mandibulae. The interspecific difference in the degree of bioerosion suggests the importance of various size of parrotfishes with diverse feeding modes to maintain healthy coral reef ecosystems. PMID:27635364
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Nanami, Atsushi
2016-01-01
Parrotfishes (family Labridae: Scarini) are regarded to have important roles for maintaining the ecosystem balance in coral reefs due to their removal of organic matter and calcic substrates by grazing. The purpose of the present study was to clarify the interspecific differences in grazing ability of five parrotfish species (Chlorurus sordidus, C. bowersi, Scarus rivulatus, S. niger and S. forsteni) in relation to interspecific differences in jaw-lever mechanics and the relative weight of the adductor mandibulae (muscles operating jaw closing). The grazing ability was calculated by using stomach contents (CaCO3 weight/organic matter weight) defined as the grazing ability index (GAI). There were significant interspecific differences in GAI (C. sordidus = C. bowersi > S. rivulatus > S. niger = S. forsteni). Teeth of C. sordidus and C. bowersi were protrusive-shape whereas teeth of S. rivulatus, S. niger and S. forsteni were flat-shape. C. sordidus and C. bowersihave jaw-lever mechanics producing a greater biting force and have a larger weight of adductor mandibulae. S. rivulatus has jaw-lever mechanics producing a greater biting force but a smaller weight of adductor mandibulae that produce an intermediate biting force. In contrast, S. niger and S. forsteni have jaw-lever mechanics producing a lesser biting force and have a smaller weight of adductor mandibulae. Feeding rates and foray size of S. rivulatus, S. niger and S. forsteni were greater than C. sordidus and C. bowersi. The degree in bioerosion (GAI × feeding rate) was the largest for S. rivulatusand the smallest for S. forsteni. The degree in bioerosion for C. sordidus was larger than S. niger whereas relatively equal between C. bowersi and S. niger. These results suggest that interspecific difference in GAI was explained by interspecific differences in teeth shape, jaw-lever mechanics and relative weight of adductor mandibulae. The interspecific difference in the degree of bioerosion suggests the importance of various size of parrotfishes with diverse feeding modes to maintain healthy coral reef ecosystems.
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A Case for Application Oblivious Energy-Efficient MPI Runtime
DOE Office of Scientific and Technical Information (OSTI.GOV)
Venkatesh, Akshay; Vishnu, Abhinav; Hamidouche, Khaled
Power has become the major impediment in designing large scale high-end systems. Message Passing Interface (MPI) is the {\\em de facto} communication interface used as the back-end for designing applications, programming models and runtime for these systems. Slack --- the time spent by an MPI process in a single MPI call --- provides a potential for energy and power savings, if an appropriate power reduction technique such as core-idling/Dynamic Voltage and Frequency Scaling (DVFS) can be applied without perturbing application's execution time. Existing techniques that exploit slack for power savings assume that application behavior repeats across iterations/executions. However, an increasingmore » use of adaptive, data-dependent workloads combined with system factors (OS noise, congestion) makes this assumption invalid. This paper proposes and implements Energy Aware MPI (EAM) --- an application-oblivious energy-efficient MPI runtime. EAM uses a combination of communication models of common MPI primitives (point-to-point, collective, progress, blocking/non-blocking) and an online observation of slack for maximizing energy efficiency. Each power lever incurs time overhead, which must be amortized over slack to minimize degradation. When predicted communication time exceeds a lever overhead, the lever is used {\\em as soon as possible} --- to maximize energy efficiency. When mis-prediction occurs, the lever(s) are used automatically at specific intervals for amortization. We implement EAM using MVAPICH2 and evaluate it on ten applications using up to 4096 processes. Our performance evaluation on an InfiniBand cluster indicates that EAM can reduce energy consumption by 5--41\\% in comparison to the default approach, with negligible (less than 4\\% in all cases) performance loss.« less
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Wright, Jennifer M; Ren, Suelynn; Constantin, Annie; Clarke, Paul B S
2018-03-01
Nicotine and D-amphetamine can strengthen reinforcing effects of unconditioned visual stimuli. We investigated whether these reinforcement-enhancing effects reflect a slowing of stimulus habituation and depend on food restriction. Adult male rats pressed an active lever to illuminate a cue light during daily 60-min sessions. Depending on the experiment, rats were challenged with fixed or varying doses of D-amphetamine (0.25-2 mg/kg IP) and nicotine (0.025-0.2 mg/kg SC) or with the tobacco constituent norharman (0.03-10 μg/kg IV). Experiment 1 tested for possible reinforcement-enhancing effects of D-amphetamine and norharman. Experiment 2 investigated whether nicotine and amphetamine inhibited the spontaneous within-session decline in lever pressing. Experiment 3 assessed the effects of food restriction. Amphetamine (0.25-1 mg/kg) and nicotine (0.1 mg/kg) increased active lever pressing specifically (two- to threefold increase). The highest doses of nicotine and amphetamine also affected inactive lever responding (increase and decrease, respectively). With the visual reinforcer omitted, responding was largely extinguished. Neither drug appeared to slow habituation, as assessed by the within-session decline in lever pressing, and reinforcement-enhancing effects still occurred if the drugs were given after this decline had occurred. Food restriction enhanced the reinforcement-enhancing effect of amphetamine but not that of nicotine. Responding remained goal-directed after several weeks of testing. Low doses of D-amphetamine and nicotine produced reinforcement enhancement even in free-feeding subjects, independent of the spontaneous within-session decline in responding. Reinforcement enhancement by amphetamine, but not nicotine, was enhanced by concurrent subchronic food restriction.
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Drozd, Robert; Cieslak, Przemyslaw E.; Rychlik, Michal; Rodriguez Parkitna, Jan; Rygula, Rafal
2016-01-01
Although the cognitive theory has implicated judgment bias in various psychopathologies, its role in decision making under risk remains relatively unexplored. In the present study, we assessed the effects of cognitive judgment bias on risky choices in rats. First, we trained and tested the animals on the rat version of the probability-discounting (PD) task. During discrete trials, the rats chose between two levers; a press on the “small/certain” lever always resulted in the delivery of one reward pellet, whereas a press on the “large/risky” lever resulted in the delivery of four pellets. However, the probability of receiving a reward from the “large/risky” lever gradually decreased over the four trial blocks. Subsequently, the rats were re-trained and evaluated on a series of ambiguous-cue interpretation (ACI) tests, which permitted their classification according to the display of “optimistic” or “pessimistic” traits. Because dopamine (DA) has been implicated in both: risky choices and optimism, in the last experiment, we compared the reactivity of the dopaminergic system in the “optimistic” and “pessimistic” animals using the apomorphine (APO; 2 mg/kg s.c.) sensitivity test. We demonstrated that as risk increased, the proportion of risky lever choices decreased significantly slower in “optimists” compared with “pessimists” and that these differences between the two groups of rats were associated with different levels of dopaminergic system reactivity. Our findings suggest that cognitive judgment bias, risky decision-making and DA are linked, and they provide a foundation for further investigation of the behavioral traits and cognitive processes that influence risky choices in animal models. PMID:27601984
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Preference pulses and the win-stay, fix-and-sample model of choice.
Hachiga, Yosuke; Sakagami, Takayuki; Silberberg, Alan
2015-11-01
Two groups of six rats each were trained to respond to two levers for a food reinforcer. One group was trained on concurrent variable-ratio 20 extinction schedules of reinforcement. The second group was trained on a concurrent variable-interval 27-s extinction schedule. In both groups, lever-schedule assignments changed randomly following reinforcement; a light cued the lever providing the next reinforcer. In the next condition, the light cue was removed and reinforcer assignment strictly alternated between levers. The next two conditions redetermined, in order, the first two conditions. Preference pulses, defined as a tendency for relative response rate to decline to the just-reinforced alternative with time since reinforcement, only appeared during the extinction schedule. Although the pulse's functional form was well described by a reinforcer-induction equation, there was a large residual between actual data and a pulse-as-artifact simulation (McLean, Grace, Pitts, & Hughes, 2014) used to discern reinforcer-dependent contributions to pulsing. However, if that simulation was modified to include a win-stay tendency (a propensity to stay on the just-reinforced alternative), the residual was greatly reduced. Additional modifications of the parameter values of the pulse-as-artifact simulation enabled it to accommodate the present results as well as those it originally accommodated. In its revised form, this simulation was used to create a model that describes response runs to the preferred alternative as terminating probabilistically, and runs to the unpreferred alternative as punctate with occasional perseverative response runs. After reinforcement, choices are modeled as returning briefly to the lever location that had been just reinforced. This win-stay propensity is hypothesized as due to reinforcer induction. © Society for the Experimental Analysis of Behavior.
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Wallin-Miller, Kathryn; Li, Grace; Kelishani, Diana; Wood, Ruth I
2018-06-01
Anabolic-androgenic steroid (AAS) abuse is implicated in maladaptive decision making such as increased risk taking and problem gambling. Endogenous testosterone correlates with economic risk taking in both the stock market (Coates & Herbert, 2008) and in the laboratory, as measured by the Iowa Gambling Task (Stanton, Liening, & Schultheiss, 2011). Additionally, AAS use has been associated with problem gambling behavior in adolescents (Proimos, DuRant, Pierce, & Goodman, 1998). Thus, AAS may impair economic decision making. However, studies of human AAS users cannot control for preexisting risky behavior or normalize androgen levels. Accordingly, the present study investigated AAS effects on decision making in rats using a novel, balanced rodent model of the IGT. Adolescent male Long-Evans rats were treated chronically with high-dose testosterone (7.5 mg/kg) or vehicle (13% cyclodextrin in water) sc, and trained to work for sugar pellets in an operant chamber equipped with 4 levers, each associated with a different schedule of reward magnitude (number of pellets), probability, and punishment (time-out) duration. By RM-ANOVA, there was a main effect of lever (F3,78 = 25.33, p < .05), such that all rats preferred lever L4 offering a large reward (4 pellets), but with low probability (45%) and a long (35 sec) time-out. There was also a significant interaction of testosterone × lever (F3,78 = 2.78, p < .05), with testosterone increasing preference for L4 and decreasing preference for the other levers, relative to vehicle-treated controls. These data extend our previous findings of altered decision making in AAS-treated rats, and suggest that AAS may alter economic decision making in human users. (PsycINFO Database Record (c) 2018 APA, all rights reserved).
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Effects of ethanol on Pavlovian autoshaping in rats.
Tomie, A; Cunha, C; Mosakowski, E M; Quartarolo, N M; Pohorecky, L A; Benjamin, D
1998-09-01
Approach responses, consummatory behaviors, and directed motor responses maintained by food reward resemble autoshaping CRs and are increased by lower doses of ethanol. This study evaluated the effects of presession i.p. injections of ethanol doses (0.00, 0.25, 0.50, 0.70. or 1.00 g/kg) on the acquisition of lever-press autoshaping CR performance in groups of male Long-Evans hooded rats. Paired groups received 15 daily sessions of Pavlovian autoshaping procedures, wherein the insertion of a retractable lever for 5 s (CS) was followed by the response-independent presentation of food (US). Ethanol facilitated lever-press autoshaping CR acquisition, as revealed by dose-related increases in the number of trials on which CRs were performed. The form of the dose-effect curve was inverted U-shaped with maximal responding induced during sessions 1-5 by the 0.70 g/kg ethanol dose. A similar dose-effect curve was observed during sessions 11-15, revealing that the effects of ethanol on autoshaping CR performance were relatively stable. A pseudoconditioning control group injected presession with 0.50 g/kg ethanol received training wherein the food US was presented randomly with respect to the lever CS. Few lever-presses were performed by the Random 0.50 group, indicating that ethanol's effects on autoshaping CR acquisition and maintenance observed in the Paired 0.50 group were not due to its psychomotor activating effects. A non-injection control group performed more autoshaping CRs than did the control group injected presession with saline, indicating that daily presession i.p. injections per se suppress autoshaping CR performance. Results reveal that low doses of ethanol enhance Pavlovian conditioning of directed motor and consummatory-like responding maintained by food reward. Implications for autoshaping accounts of impulsivity and drug abuse are considered.
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Carroll, M E; Lac, S T
1993-01-01
The purpose of this experiment was to examine the effects of a nondrug alternative reinforcer and feeding conditions on the acquisition of cocaine self-administration. Rats were autoshaped to press a lever that resulted in a 0.2 mg/kg i.v. cocaine infusion. Responses on the lever were monitored during six consecutive autoshaping sessions that occurred each day. A retractable lever was inserted into the operant chamber on a random time 60 s schedule 10 times per session for six sessions that began each hour. Each day the six autoshaping sessions were followed by a 6-h cocaine self-administration session. During self-administration the lever remained extended, and each response on the lever resulted in a cocaine infusion (0.2 mg/kg). The criterion for acquisition of cocaine-reinforced behavior was met when there were 5 consecutive days during which the mean number of infusions during the 6-h self-administration session was at least 100. This procedure was repeated daily until the criterion was met or 30 days elapsed. The rats were also trained to respond on lick-operated automatic drinking devices that delivered 0.05 ml water or a glucose and saccharin solution (G + S) contingent upon each lick response. Five groups of 12-14 rats were compared. The first four groups constituted a 2 x 2 factorial design whereby either G + S or water was available in the home cage for 3 weeks before autoshaping began and G + S or water was available in the operant chamber during autoshaping. These groups were limited to 20 g food per day and all had free access to water.(ABSTRACT TRUNCATED AT 250 WORDS)
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Hellig, Christoph J; Kerschbaumer, Michaela; Sefc, Kristina M; Koblmüller, Stephan
2010-07-01
The morphological versatility of the pharyngeal jaw of cichlid fishes is assumed to represent a key factor facilitating their unparalleled trophic diversification and explosive radiation. It is generally believed that the functional design of an organism relates to its ecology, and thus, specializations to different diets are typically associated with distinct morphological designs, especially manifested in the cichlids' pharyngeal jaw apparatus. Thereby, the lower pharyngeal jaw (LPJ) incorporates some of the most predictive features for distinct diet-related morphotypes. Thus, considering that piscivorous cichlids experience an ontogenetic dietary shift from typically various kinds of invertebrates to fish, concomitant morphological changes in the LPJ are expected. Using Lepidiolamprologus elongatus, a top predator in the shallow rocky habitat of Lake Tanganyika, as model, and applying geometric and traditional morphometric techniques, we demonstrate an allometric change in ontogenetic LPJ shape development coinciding with the completion of the dietary shift toward piscivory. The piscivorous LPJ morphotype is initiated in juvenile fish by increasing elongation and narrowing of the LPJ and--when the fish reach a size of 80-90 mm standard length--further refined by the elongation of the posterior muscular processes, which serve as insertion for the fourth musculus levator externus. The enlarged muscular processes of the fully mature piscivorous morphotype provide for the construction of a powerful lever system, which allows the large individuals to process large prey fish and rely on exclusive piscivory.
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NASA Astrophysics Data System (ADS)
Hellig, Christoph J.; Kerschbaumer, Michaela; Sefc, Kristina M.; Koblmüller, Stephan
2010-07-01
The morphological versatility of the pharyngeal jaw of cichlid fishes is assumed to represent a key factor facilitating their unparalleled trophic diversification and explosive radiation. It is generally believed that the functional design of an organism relates to its ecology, and thus, specializations to different diets are typically associated with distinct morphological designs, especially manifested in the cichlids’ pharyngeal jaw apparatus. Thereby, the lower pharyngeal jaw (LPJ) incorporates some of the most predictive features for distinct diet-related morphotypes. Thus, considering that piscivorous cichlids experience an ontogenetic dietary shift from typically various kinds of invertebrates to fish, concomitant morphological changes in the LPJ are expected. Using Lepidiolamprologus elongatus, a top predator in the shallow rocky habitat of Lake Tanganyika, as model, and applying geometric and traditional morphometric techniques, we demonstrate an allometric change in ontogenetic LPJ shape development coinciding with the completion of the dietary shift toward piscivory. The piscivorous LPJ morphotype is initiated in juvenile fish by increasing elongation and narrowing of the LPJ and—when the fish reach a size of 80-90 mm standard length—further refined by the elongation of the posterior muscular processes, which serve as insertion for the fourth musculus levator externus. The enlarged muscular processes of the fully mature piscivorous morphotype provide for the construction of a powerful lever system, which allows the large individuals to process large prey fish and rely on exclusive piscivory.
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NASA Astrophysics Data System (ADS)
Mirchi, Ali; Watkins, David W.; Huckins, Casey J.; Madani, Kaveh; Hjorth, Peder
2014-09-01
Biotic homogenization, a de facto symptom of a global biodiversity crisis, underscores the urgency of reforming water resources management to focus on the health and viability of ecosystems. Global population and economic growth, coupled with inadequate investment in maintenance of ecological systems, threaten to degrade environmental integrity and ecosystem services that support the global socioeconomic system, indicative of a system governed by the Growth and Underinvestment (G&U) archetype. Water resources management is linked to biotic homogenization and degradation of system integrity through alteration of water systems, ecosystem dynamics, and composition of the biota. Consistent with the G&U archetype, water resources planning primarily treats ecological considerations as exogenous constraints rather than integral, dynamic, and responsive parts of the system. It is essential that the ecological considerations be made objectives of water resources development plans to facilitate the analysis of feedbacks and potential trade-offs between socioeconomic gains and ecological losses. We call for expediting a shift to ecosystem-based management of water resources, which requires a better understanding of the dynamics and links between water resources management actions, ecological side-effects, and associated long-term ramifications for sustainability. To address existing knowledge gaps, models that include dynamics and estimated thresholds for regime shifts or ecosystem degradation need to be developed. Policy levers for implementation of ecosystem-based water resources management include shifting away from growth-oriented supply management, better demand management, increased public awareness, and institutional reform that promotes adaptive and transdisciplinary management approaches.
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Gilbert, Jeremy; Campos, Arlene C.; Kline, Nicole; Ashby, Charles R.; Hagan, Jim J.; Heidbreder, Christian A.; Gardner, Eliot L.
2013-01-01
Rationale The dopamine (DA) D3 receptor is preferentially expressed in the mesolimbic system. We have previously shown that selective D3 receptor blockade by the novel D3 antagonist SB-277011A inhibits cocaine’s reinforcing action and cocaine-induced reinstatement of cocaine-seeking behavior. Objective In the present study, we investigated whether SB-277011A similarly inhibits stress-induced reinstatement of cocaine-seeking behavior. Methods Rats were allowed to self-administer cocaine (0.5 mg/kg per infusion, 3 h per session) for 10–14 days, followed by a once-daily extinction session for 7–14 days during which saline was substituted for cocaine. Extinction criteria were fewer than ten lever-presses per 3-h session for at least 3 consecutive days. After cocaine-seeking behavior was extinguished, each animal was tested twice for footshock-stress-induced reinstatement, once with vehicle (25% hydroxypropyl-β-cyclodextrin) and once with one of three doses of SB-277011A in counterbalanced fashion. Results During the last 3 days of cocaine self-administration (SA), active lever-presses were approximately 100 per session under fixed-ratio 2 reinforcement (~25 mg/kg cocaine per session). After extinction, intermittent footshock (10 min, 0.5 mA, 0.5 s on with a mean inter-shock interval of 40 s) robustly reinstated the cocaine-seeking behavior (8.4±3.6 active lever-presses in last extinction session to 35.3±5.2 in animals after footshock stress). Intraperitoneal (IP) injections of SB-277011A (3, 6, and 12 mg/kg) dose-dependently blocked stress-induced reinstatement of cocaine-seeking. Reinstatement was also blocked by microinjections of SB-277011A (1.5 μg/0.5 μl per side) bilaterally into the nucleus accumbens, but not into the dorsal striatum. Conclusions The mesolimic DA D3 receptor plays an important role in mediating stress-induced reinstatement. PMID:15083257
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Brunzell, Darlene H; Boschen, Karen E; Hendrick, Elizabeth S; Beardsley, Patrick M; McIntosh, J Michael
2010-01-01
β2 subunit containing nicotinic acetylcholine receptors (β2*nAChRs; asterisk (*) denotes assembly with other subunits) are critical for nicotine self-administration and nicotine-associated dopamine (DA) release that supports nicotine reinforcement. The α6 subunit assembles with β2 on DA neurons where α6β2*nAChRs regulate nicotine-stimulated DA release at neuron terminals. Using local infusion of α-conotoxin MII (α-CTX MII), an antagonist with selectivity for α6β2*nAChRs, the purpose of these experiments was to determine if α6β2*nAChRs in the nucleus accumbens (NAc) shell are required for motivation to self-administer nicotine. Long-Evans rats lever-pressed for 0.03 mg/kg, i.v., nicotine accompanied by light+tone cues (NIC) or for light+tone cues unaccompanied by nicotine (CUEonly). Following extensive training, animals were tested under a progressive ratio (PR) schedule that required an increasing number of lever presses for each nicotine infusion and/or cue delivery. Immediately before each PR session, rats received microinfusions of α-CTX MII (0, 1, 5, or 10 pmol per side) into the NAc shell or the overlying anterior cingulate cortex. α-CTX MII dose dependently decreased break points and number of infusions earned by NIC rats following infusion into the NAc shell but not the anterior cingulate cortex. Concentrations of α-CTX MII that were capable of attenuating nicotine self-administration did not disrupt locomotor activity. There was no effect of infusion on lever pressing in CUEonly animals and NAc infusion α-CTX MII did not affect locomotor activity in an open field. These data suggest that α6β2*nAChRs in the NAc shell regulate motivational aspects of nicotine reinforcement but not nicotine-associated locomotor activation. PMID:19890263
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Isokinetic Evaluation of the Hip Flexor and Extensor Muscles: A Systematic Review.
Zapparoli, Fabricio Yuri; Riberto, Marcelo
2017-11-01
Isokinetic dynamometry testing is a safe and reliable method accepted as the "gold standard" in the evaluation of muscle strength in the open kinetic chain. Isokinetic hip examinations face problems in the standardization of the position of the equipment axis, in the individual being examined, and in the adjustment of the lever arm and in stabilization strategies for the patients during the tests. Identification of the methodologic procedures with best reproducibility is also needed. To review the literature to evaluate the parameters used for the isokinetic evaluation of the hip flexor and extensor muscles and its reproducibility. This is a systematic literature review of the Cochrane, LILACS, PEDro, PubMed, and SciELO databases. The inclusion criteria were articles on the evaluation of hip flexor and/or extensor muscular strength with an isokinetic dynamometer and articles that analyzed the ICC or Pearson's reproducibility. The information extracted was positioning of the patient; positioning of the dynamometer axis; positioning of the lever arm; angular speed; sample size, pathology; type of contraction; and ICC and Pearson's results. 204 articles were found, from which 14 were selected that evaluated hip flexor and extensor muscles, involving 550 individuals who were submitted to an isokinetic hip evaluation. Five articles obtained the best result in reproducibility and had their methodology analyzed. To obtain better reproducibility of the isokinetic evaluation of the hip flexor and extensor muscles, the following recommendations must be followed: the individual must be positioned in the supine position and the dynamometer axis must be aligned with the greater trochanter of the femur. The positioning of the lever arm must be in the most distal region of the thigh possible. The angular speed used to analyze torque peak and muscle work was 60°/s, and to evaluate the muscle power it was 180°/s, with concentric and eccentric contractions being analyzed.
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Hanlon, Erin C; Baldo, Brian A; Sadeghian, Ken; Kelley, Ann E
2004-03-01
Previous work has shown that stimulation of GABAergic, opioid, or dopaminergic systems within the nucleus accumbens modulates food intake and food-seeking behavior. However, it is not known whether such stimulation mimics a motivational state of food deprivation that commonly enables animals to learn a new operant response to obtain food. In order to address this question, acquisition of lever pressing for food in hungry animals was compared with acquisition in non-food-deprived rats subjected to various nucleus accumbens drug treatments. All animals were given the opportunity to learn an instrumental response (a lever press) to obtain a food pellet. Prior to training, ad lib-fed rats were infused with the gamma-aminobutyric acid (GABA)A agonist muscimol (100 ng/0.5 microl per side) or the mu-opioid receptor agonist D-Ala2, N-me-Phe4, Gly-ol5-enkephalin (DAMGO, 0.25 microg/0.5 microl per side), or saline into the nucleus accumbens shell (AcbSh). The indirect dopamine agonist amphetamine (10 microg/0.5 microl per side) was infused into the AcbSh or nucleus accumbens core (AcbC) of ad lib-fed rats. An additional group was food deprived and infused with saline in the AcbSh. Chow and sugar pellet intake responses after drug treatments were also evaluated in free-feeding tests. Muscimol, DAMGO, or amphetamine did not facilitate acquisition of lever pressing for food, despite clearly increasing food intake in free-feeding tests. In contrast, food-deprived animals rapidly learned the task. These findings suggest that pharmacological stimulation of any of these neurochemical systems in isolation is insufficient to enable acquisition of a food-reinforced operant task. Thus, these selective processes, while likely involved in control of food intake and food-seeking behavior, appear unable to recapitulate the conditions necessary to mimic the state of negative energy balance.
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Liu, Xiu
2014-01-01
Rationale Overeating beyond individuals’ homeostatic needs critically contributes to obesity. The neurobehavioral mechanisms underlying the motivation to consume excessive foods with high calories are not fully understood. Objective The present study examined whether a pharmacological stressor, yohimbine enhances the motivation to procure food reward with an emphasis on comparisons between standard lab chow and high-fat foods. The effects of corticotropin-releasing factor receptor (CRF1) blockade by a CFR1 selective antagonist NBI on the stress-enhanced motivation for food reward were also assessed. Methods Male Sprague-Dawley rats with chow available ad libitum in their home cages were trained to press a lever under a progressive-ratio schedule for deliveries of either standard or high-fat food pellets. For testing yohimbine stress effects, rats received an intraperitoneal administration of yohimbine 10 min before start of the test sessions. For testing effects of CRF1 receptor blockade on stress responses, NBI was administered 20 min prior to yohimbine challenge. Results The rats emitted higher levels of lever responses to procure the high-fat food pellets compared with their counterparts on standard food pellets. Yohimbine challenge facilitated lever responses for the reward in all of the rats, whereas the effect was more robust in the rats on high-fat food pellets compared with their counterparts on standard food pellets. An inhibitory effect of pretreatment with NBI was observed on the enhancing effect of yohimbine challenge but not on the responses under baseline condition without yohimbine administration. Conclusions Stress challenge significantly enhanced the motivation of satiated rats to procure extra food reward, especially the high-fat food pellets. Activation of CRF1 receptors is required for the stress-enhanced motivation for food reward. These results may have implications for our better understanding of the biobehavioral mechanisms of overeating and obesity. PMID:25510859
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Fowler, Christie D.; Kenny, Paul J.
2011-01-01
Intravenous nicotine self-administration is the most direct measure of nicotine reinforcement in laboratory animals, but this procedure has proven difficult to establish in mice. We found that stable responding for nicotine in C57BL6/J mice was facilitated by prior instrumental training for food reward, initial exposure of mice to a lower unit dose of nicotine (0.03 mg/kg/infusion) before access to higher doses, a slower rate of drug delivery (3-sec versus 1-sec infusion), consistency in schedule of daily testing, and low extraneous noise during testing. Under these conditions, we found that mice lever-pressing for nicotine (0.03–0.4 mg/kg/infusion; 60-min test sessions) under a fixed-ratio 5 time-out 20-sec (FR5TO20) reinforcement schedule consumed the drug according to an inverted ‘U’-shaped dose-response curve. Mice switched their responding onto a previously non-reinforced lever to continue earning nicotine infusions when the active/inactive lever assignment was reversed. The nicotinic acetylcholine receptor (nAChR) antagonist mecamylamine decreased responding for nicotine, but not food rewards, verifying that nAChRs regulate nicotine self-administration in mice. The cue-light paired with nicotine delivery did not support responding when delivered independently of nicotine infusions, further verifying that mice responded selectivity for the drug. Nicotine-seeking responses extinguished when nicotine infusions and the cue-light were withheld, and exposure to the cue-light reinstated responding. Finally, mice without prior instrumental food training acquired stable responding for nicotine under the FR5TO20 schedule, but required a greater number of sessions. These data demonstrate that nicotine is an effective reinforcer in mice and establish conditions under which the drug is reliably self-administered by mice. PMID:21640128
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Liu, Xiu
2015-06-01
Overeating beyond individuals' homeostatic needs critically contributes to obesity. The neurobehavioral mechanisms underlying the motivation to consume excessive foods with high calories are not fully understood. The present study examined whether a pharmacological stressor, yohimbine, enhances the motivation to procure food reward with an emphasis on comparisons between standard lab chow and high-fat foods. The effects of corticotropin-releasing factor (CRF) receptor blockade by a CRF1-selective antagonist NBI on the stress-enhanced motivation for food reward were also assessed. Male Sprague-Dawley rats with chow available ad libitum in their home cages were trained to press a lever under a progressive ratio schedule for deliveries of either standard or high-fat food pellets. For testing yohimbine stress effects, rats received an intraperitoneal administration of yohimbine 10 min before start of the test sessions. For testing effects of CRF1 receptor blockade on stress responses, NBI was administered 20 min prior to yohimbine challenge. The rats emitted higher levels of lever responses to procure the high-fat food pellets compared with their counterparts on standard food pellets. Yohimbine challenge facilitated lever responses for the reward in all of the rats, whereas the effect was more robust in the rats on high-fat food pellets compared with their counterparts on standard food pellets. An inhibitory effect of pretreatment with NBI was observed on the enhancing effect of yohimbine challenge but not on the responses under baseline condition without yohimbine administration. Stress challenge significantly enhanced the motivation of satiated rats to procure extra food reward, especially the high-fat food pellets. Activation of CRF1 receptors is required for the stress-enhanced motivation for food reward. These results may have implications for our better understanding of the biobehavioral mechanisms of overeating and obesity.
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Worden, Lila T.; Shahriari, Mona; Farrar, Andrew M.; Sink, Kelly S.; Hockemeyer, Jörg; Müller, Christa E.
2010-01-01
Rationale Brain dopamine (DA) participates in the modulation of instrumental behavior, including aspects of behavioral activation and effort-related choice behavior. Rats with impaired DA transmission reallocate their behavior away from food-seeking behaviors that have high response requirements, and instead select less effortful alternatives. Although accumbens DA is considered a critical component of the brain circuitry regulating effort-related choice behavior, emerging evidence demonstrates a role for adenosine A2A receptors. Objective Adenosine A2A receptor antagonism has been shown to reverse the effects of DA antagonism. The present experiments were conducted to determine if this effect was dependent upon the subtype of DA receptor that was antagonized to produce the changes in effort-related choice. Materials and methods The adenosine A2A receptor antagonist MSX-3 (0.5–2.0 mg/kg IP) was assessed for its ability to reverse the effects of the D1 family antagonist SCH39166 (ecopipam; 0.2 mg/kg IP) and the D2 family antagonist eticlopride (0.08 mg/kg IP), using a concurrent lever pressing/chow feeding procedure. Results MSX-3 produced a substantial dose-related reversal of the effects of eticlopride on lever pressing and chow intake. At the highest dose of MSX-3, there was a complete reversal of the effects of eticlopride on lever pressing. In contrast, MSX-3 produced only a minimal attenuation of the effects of SCH39166, as measured by regression and effect size analyses. Conclusions The greater ability of MSX-3 to reverse the effects of D2 vs. D1 blockade may be related to the colocalization of D2 and adenosine A2A receptors on the same population of striatal neurons. PMID:19048234
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Leadership Perspective: Bringing Nursing Back to the Future Through People-Powered Care.
Sharkey, Shirlee; Lefebre, Nancy
2017-01-01
At a time when there is a growing interest in person- and family-centred care and integrated community-based models, the unique strengths and expertise of home care nursing is a strategic lever for change across all healthcare settings. In this paper, we explore the theme of people-powered care as a universal starting point - a new approach to health and wellness that is anchored in the strengths of people, their networks and the patterns of everyday life. Leveraging key insights from home and community care, along with broader societal shifts towards personalization and empowerment, we discuss how nurses in all areas of the system can lead the way by empowering staff, patients and their families. Finally, we look at the implications for nursing leadership including how our knowledge, skills and abilities must continue to evolve to effectively impact change and enable this vital transformation to occur.
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Mark, T A; Gallistel, C R
1994-01-01
Rats responded on concurrent variable interval schedules of brain stimulation reward in 2-trial sessions. Between trials, there was a 16-fold reversal in the relative rate of reward. In successive, narrow time windows, the authors compared the ratio of the times spent on the 2 levers to the ratio of the rewards received. Time-allocation ratios tracked wide, random fluctuations in the reward ratio. The adjustment to the midsession reversal in relative rate of reward was largely completed within 1 interreward interval on the leaner schedule. Both results were unaffected by a 16-fold change in the combined rates of reward. The large, rapid, scale-invariant shifts in time-allocation ratios that underlie matching behavior imply that the subjective relative rate of reward can be determined by a very few of the most recent interreward intervals and that this estimate can directly determine the ratio of the expected stay durations.
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Polarization masks: concept and initial assessment
NASA Astrophysics Data System (ADS)
Lam, Michael; Neureuther, Andrew R.
2002-07-01
Polarization from photomasks can be used as a new lever to improve lithographic performance in both binary and phase-shifting masks (PSMs). While PSMs manipulate the phase of light to control the temporal addition of electric field vectors, polarization masks manipulate the vector direction of electric field vectors to control the spatial addition of electric field components. This paper explores the theoretical possibilities of polarization masks, showing that it is possible to use bar structures within openings on the mask itself to polarize incident radiation. Rigorous electromagnetic scattering simulations using TEMPEST and imaging with SPLAT are used to give an initial assessment on the functionality of polarization masks, discussing the polarization quality and throughputs achieved with the masks. Openings between 1/8 and 1/3 of a wavelength provide both a low polarization ratio and good transmission. A final overall throughput of 33% - 40% is achievable, corresponding to a dose hit of 2.5x - 3x.
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Zhang, Min; Balmadrid, Christian; Kelley, Ann E
2003-04-01
The current studies were designed to evaluate whether incentive motivation for palatable food is altered after manipulations of opioid, GABAergic, and dopaminergic transmission within the nucleus accumbens. A progressive ratio schedule was used to measure lever-pressing for sugar pellets after microinfusion of drugs into the nucleus accumbens in non-food-deprived rats. The mu opioid agonist D-Ala2, NMe-Phe4, Glyo15-enkephalin and the indirect dopamine agonist amphetamine induced a marked increase in break point and correct lever-presses; the GABA(A) agonist muscimol did not affect breakpoint or lever-presses. The data suggest that opioid, dopaminergic, and GABAergic systems within the accumbens differentially modulate food-seeking behavior through mechanisms related to hedonic evaluation of food, incentive salience, and control of motor feeding circuits, respectively.
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Clark, Richard P.; Smits, Alexander J.
2009-01-01
An apparatus is described for the measurement of unsteady thrust and propulsive efficiency produced by biologically inspired oscillating hydrodynamic propulsors. Force measurement is achieved using a strain-gauge-based force transducer, augmented with a lever to amplify or attenuate the applied force and control the measurement sensitivity and natural frequency of vibration. The lever can be used to tune the system to a specific application and it is shown that, using the lever, the stiffness can be made to increase more rapidly than the measurement sensitivity decreases. Efficiency is computed from measurements of the time-averaged power imparted to the fluid. The apparatus is applied to two different propulsors, demonstrating the versatility of the system; wake visualizations are examined, which provide insight into the physical mechanisms of efficient propulsion. PMID:19946574
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Torres, Carmen; Glueck, Amanda C; Conrad, Shannon E; Morón, Ignacio; Papini, Mauricio R
2016-09-22
The dorsomedial striatum (DMS) has been implicated in the acquisition of reward representations, a proposal leading to the hypothesis that it should play a role in situations involving reward loss. We report the results of an experiment in which the effects of DMS excitotoxic lesions were tested in consummatory successive negative contrast (reward devaluation), autoshaping training with partial vs. continuous reinforcement (reward uncertainty), and appetitive extinction (reward omission). Animals with DMS lesions exhibited reduced lever pressing responding, but enhanced goal entries, during partial reinforcement training in autoshaping. However, they showed normal negative contrast, acquisition under continuous reinforcement (CR), appetitive extinction, and response facilitation in early extinction trials. Open-field testing also indicated normal motor behavior. Thus, DMS lesions selectively affected the behavioral adjustment to a situation involving reward uncertainty, producing a behavioral reorganization according to which goal tracking (goal entries) became predominant at the expense of sign tracking (lever pressing). This pattern of results shows that the function of the DMS in situations involving reward loss is not general, but restricted to reward uncertainty. We suggest that a nonassociative, drive-related process induced by reward uncertainty requires normal output from DMS neurons. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.
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Hafenbreidel, Madalyn; Todd, Carolynn Rafa; Twining, Robert C.; Tuscher, Jennifer J.; Mueller, Devin
2014-01-01
Rationale Extinction of drug seeking is facilitated by NMDA receptor (NMDAr) agonists, but it remains unclear whether extinction is dependent on NMDAr activity. Objectives We investigated the necessity of NMDArs for extinction of cocaine seeking, and whether extinction altered NMDAr expression within extinction-related neuroanatomical loci. Methods Rats were trained to lever press for i.v. infusions of cocaine or sucrose reinforcement prior to extinction training or withdrawal. Results Administration of the NMDAr competitive antagonist CPP prior to four brief extinction sessions impaired subsequent extinction retention. In contrast, post-extinction administration of the NMDAr coagonist D-serine attenuated lever pressing across days as compared to saline administration, indicative of facilitated consolidation of extinction. Furthermore, expression of the NMDAr subunits, GluN2A and GluN2B, was not altered in the ventromedial prefrontal cortex. However, both GluN2A and GluN2B subunit expression in the nucleus accumbens was increased following cocaine self-administration, and this increased expression was relatively resistant to modulation by extinction. Conclusions Our findings demonstrate that extinction of cocaine seeking is bidirectionally mediated by NMDArs and suggest that selective modulation of NMDAr activity could facilitate extinction-based therapies for treatment of cocaine abuse. PMID:24847958
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Performance on a strategy set shifting task in rats following adult or adolescent cocaine exposure
Kantak, Kathleen M.; Barlow, Nicole; Tassin, David H.; Brisotti, Madeline F.; Jordan, Chloe J
2014-01-01
Rationale Neuropsychological testing is widespread in adult cocaine abusers, but lacking in teens. Animal models may provide insight into age-related neuropsychological consequences of cocaine exposure. Objectives Determine whether developmental plasticity protects or hinders behavioral flexibility after cocaine exposure in adolescent vs. adult rats. Methods Using a yoked-triad design, one rat controlled cocaine delivery and the other two passively received cocaine or saline. Rats controlling cocaine delivery (1.0 mg/kg) self-administered for 18 sessions (starting P37 or P77), followed by 18 drug-free days. Rats next were tested in a strategy set shifting task, lasting 11–13 sessions. Results Cocaine self-administration did not differ between age groups. During initial set formation, adolescent-onset groups required more trials to reach criterion and made more errors than adult-onset groups. During the set shift phase, rats with adult-onset cocaine self-administration experience had higher proportions of correct trials and fewer perseverative + regressive errors than age-matched yoked-controls or rats with adolescent-onset cocaine self-administration experience. During reversal learning, rats with adult-onset cocaine experience (self-administered or passive) required fewer trials to reach criterion and the self-administering rats made fewer perseverative + regressive errors than yoked-saline rats. Rats receiving adolescent-onset yoked-cocaine had more trial omissions and longer lever press reaction times than age-matched rats self-administering cocaine or receiving yoked-saline. Conclusions Prior cocaine self-administration may impair memory to reduce proactive interference during set shifting and reversal learning in adult-onset but not adolescent-onset rats (developmental plasticity protective). Passive cocaine may disrupt aspects of executive function in adolescent-onset but not adult-onset rats (developmental plasticity hinders). PMID:24800898
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ERIC Educational Resources Information Center
Mazur, James E.
2005-01-01
In Experiment 1 with rats, a left lever press led to a 5-s delay and then a possible reinforcer. A right lever press led to an adjusting delay and then a certain reinforcer. This delay was adjusted over trials to estimate an indifference point, or a delay at which the two alternatives were chosen about equally often. Indifference points increased…
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Rats' Memory for Time and Relational Responding in the Duration-Comparison Procedure
ERIC Educational Resources Information Center
Santi, Angelo; Hoover, Claire; Simmons, Sabrina
2011-01-01
Rats were trained in a duration-comparison task to press one lever if the comparison duration ("c") was 1.2-s shorter than a standard duration ("s"), and another lever if c was 1.2-s longer than s. The interval between s and c duration was 1 s. The 10 duration pairs used during training controlled for the absolute duration of "c" and the total…
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In vivo myosin step-size from zebrafish skeletal muscle
Ajtai, Katalin; Sun, Xiaojing; Takubo, Naoko; Wang, Yihua
2016-01-01
Muscle myosins transduce ATP free energy into actin displacement to power contraction. In vivo, myosin side chains are modified post-translationally under native conditions, potentially impacting function. Single myosin detection provides the ‘bottom-up’ myosin characterization probing basic mechanisms without ambiguities inherent to ensemble observation. Macroscopic muscle physiological experimentation provides the definitive ‘top-down’ phenotype characterizations that are the concerns in translational medicine. In vivo single myosin detection in muscle from zebrafish embryo models for human muscle fulfils ambitions for both bottom-up and top-down experimentation. A photoactivatable green fluorescent protein (GFP)-tagged myosin light chain expressed in transgenic zebrafish skeletal muscle specifically modifies the myosin lever-arm. Strychnine induces the simultaneous contraction of the bilateral tail muscles in a live embryo, causing them to be isometric while active. Highly inclined thin illumination excites the GFP tag of single lever-arms and its super-resolution orientation is measured from an active isometric muscle over a time sequence covering many transduction cycles. Consecutive frame lever-arm angular displacement converts to step-size by its product with the estimated lever-arm length. About 17% of the active myosin steps that fall between 2 and 7 nm are implicated as powerstrokes because they are beyond displacements detected from either relaxed or ATP-depleted (rigor) muscle. PMID:27249818
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Reichel, Carmela M.; Linkugel, Jessica D.; Bevins, Rick A.
2010-01-01
Bupropion reduces the subjective effects and cue-induced craving for methamphetamine in humans. Given these effects of bupropion on methamphetamine in humans and its widespread clinical use, a preclinical model of drug-taking was used to determine if pretreatment with bupropion would alter the acquisition of methamphetamine self-administration. During acquisition, rats were given saline or bupropion (30 or 60 mg/kg, IP) 5 min before a 60-min session. For the first 8 days, each response on the active lever produced an infusion of methamphetamine (0.025 mg/kg). Responding on the inactive lever had no programmed consequence. This FR1 schedule was then increased to an FR3 for 4 more days. In a parallel study, the identical procedures were used to test the impact of bupropion on sucrose-maintained responding. Bupropion pretreatment decreased the number of methamphetamine infusions and sucrose deliveries earned on an FR1 and FR3. However, bupropion pretreatment only delayed discrimination between the active and inactive levers in the methamphetamine self-administration rats. Discrimination between active and inactive levers was acquired in all groups in the sucrose experiment regardless of pretreatment condition. Combined, these results suggest that bupropion has a more general effect within the appetitive/reward system of the brain rather than having complete specificity for methamphetamine. PMID:18329085
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Alfa, Michelle J; Singh, Harminder; Nugent, Zoann; Duerksen, Donald; Schultz, Gale; Reidy, Carol; DeGagne, Patricia; Olson, Nancy
2017-01-01
Simulated-use buildup biofilm (BBF) model was used to assess various extraction fluids and friction methods to determine the optimal sample collection method for polytetrafluorethylene channels. In addition, simulated-use testing was performed for the channel and lever cavity of duodenoscopes. BBF was formed in polytetrafluorethylene channels using Enterococcus faecalis, Escherichia coli , and Pseudomonas aeruginosa . Sterile reverse osmosis (RO) water, and phosphate-buffered saline with and without Tween80 as well as two neutralizing broths (Letheen and Dey-Engley) were each assessed with and without friction. Neutralizer was added immediately after sample collection and samples concentrated using centrifugation. Simulated-use testing was done using TJF-Q180V and JF-140F Olympus duodenoscopes. Despite variability in the bacterial CFU in the BBF model, none of the extraction fluids tested were significantly better than RO. Borescope examination showed far less residual material when friction was part of the extraction protocol. The RO for flush-brush-flush (FBF) extraction provided significantly better recovery of E. coli ( p = 0.02) from duodenoscope lever cavities compared to the CDC flush method. We recommend RO with friction for FBF extraction of the channel and lever cavity of duodenoscopes. Neutralizer and sample concentration optimize recovery of viable bacteria on culture.
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Maguire, David R; Gerak, Lisa R; France, Charles P
2015-01-01
Opioid abusers discount delayed reinforcers more rapidly than non-users; however, it is unclear whether chronic drug administration or its discontinuation impact discounting. This study examined daily morphine administration and its discontinuation on delay discounting of food in rhesus monkeys. Responding on one lever delivered 1 food pellet immediately; responding on another lever delivered 2 food pellets either immediately or after a delay (30–120 sec) that increased within the session. Monkeys (n=3) responded for the large reinforcer when both reinforcers were delivered immediately and more for the smaller, immediately available reinforcer as delay to delivery of the large reinforcer increased. When administered acutely, morphine (0.032–5.6 mg/kg) increased trial omissions and had variable effects on choice, with small doses decreasing and large doses increasing choice of the large delayed reinforcer. Chronic morphine administration (0.1 mg/kg/day to 3.2 mg/kg twice daily) reduced choice of the large delayed reinforcer in two monkeys while increasing choice in a third monkey. Despite the development of tolerance to some effects (i.e., rightward shifts in dose-effect curves for the number of trials omitted) and evidence of mild opioid dependence (e.g., decrease in the number of trials completed as well as body weight), discontinuation of treatment did not appear to systematically impact discounting. Overall, these results suggest that repeated opioid administration causes persistent effects on choice under a delay discounting procedure; however, differences in the direction of effect among individuals suggest factors other than, or in addition to, changes in discounting might play a role. PMID:26397762
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Complex discriminative stimulus properties of (+)lysergic acid diethylamide (LSD) in C57Bl/6J mice.
Benneyworth, Michael A; Smith, Randy L; Barrett, Robert J; Sanders-Bush, Elaine
2005-06-01
The drug discrimination procedure is the most frequently used in vivo model of hallucinogen activity. Historically, most drug discrimination studies have been conducted in the rat. With the development of genetically modified mice, a powerful new tool has become available for investigating the mechanisms of drug-induced behavior. The current paper is part of an ongoing effort to determine the utility of the drug discrimination technique for evaluating hallucinogenic drugs in mice. To establish the training procedures and characterize the stimulus properties of (+)lysergic acid diethylamide (LSD) in mice. Using a two-lever drug discrimination procedure, C57Bl/6J mice were trained to discriminate 0.45 mg/kg LSD vs saline on a VI30 sec schedule of reinforcement, with vanilla-flavored Ensure serving as the reinforcer. As in rats, acquisition was orderly, but the training dose was nearly five-fold higher for mice than rats. LSD lever selection was dose-dependent. Time-course studies revealed a rapid loss of the LSD stimulus effects. The 5-HT(2A/2C) receptor agonist, 2,5-dimethoxy-4-bromoamphetamine [(-)DOB] (1.0 mg/kg), substituted fully for LSD and the 5-HT(1A) receptor agonist, 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT) (1.6 mg/kg), substituted partially for LSD. Pretreatment with the 5-HT(2A) receptor-selective antagonist, MDL 100907, or the 5-HT(1A)-selective antagonist WAY 100635, showed that each antagonist only partially blocked LSD discrimination. Substitution of 1.0 mg/kg (-)DOB for LSD was fully blocked by pretreatment with MDL 100907 but unaltered by WAY 100635 pretreatment. These data suggest that in mice the stimulus effects of LSD have both a 5-HT(2A) receptor and a 5-HT(1A) receptor component.
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Palmatier, Matthew I; Kellicut, Marissa R; Brianna Sheppard, A; Brown, Russell W; Robinson, Donita L
2014-11-01
Nicotine is a psychomotor stimulant with 'reinforcement enhancing' effects--the actions of nicotine in the brain increase responding for non-nicotine rewards. We hypothesized that this latter effect of nicotine depends on increased incentive properties of anticipatory cues; consistent with this hypothesis, multiple laboratories have reported that nicotine increases sign tracking, i.e. approach to a conditioned stimulus (CS), in Pavlovian conditioned-approach tasks. Incentive motivation and sign tracking are mediated by mesolimbic dopamine (DA) transmission and nicotine facilitates mesolimbic DA release. Therefore, we hypothesized that the incentive-promoting effects of nicotine would be impaired by DA antagonists. To test this hypothesis, separate groups of rats were injected with nicotine (0.4mg/kg base) or saline prior to Pavlovian conditioning sessions in which a CS (30s illumination of a light or presentation of a lever) was immediately followed by a sweet reward delivered in an adjacent location. Both saline and nicotine pretreated rats exhibited similar levels of conditioned approach to the reward location (goal tracking), but nicotine pretreatment significantly increased approach to the CS (sign tracking), regardless of type (lever or light). The DAD1 antagonist SCH-23390 and the DAD2/3 antagonist eticlopride reduced conditioned approach in all rats, but specifically reduced goal tracking in the saline pretreated rats and sign tracking in the nicotine pretreated rats. The non-selective DA antagonist flupenthixol reduced sign-tracking in nicotine rats at all doses tested; however, only the highest dose of flupenthixol reduced goal tracking in both nicotine and saline groups. The reductions in conditioned approach behavior, especially those by SCH-23390, were dissociated from simple motor suppressant effects of the antagonists. These experiments are the first to investigate the effects of dopaminergic drugs on the facilitation of sign-tracking engendered by nicotine and they implicate dopaminergic systems both in conditioned approach as well as the incentive-promoting effects of nicotine. Copyright © 2014 Elsevier Inc. All rights reserved.
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Pump control system for windmills
Avery, Don E.
1983-01-01
A windmill control system having lever means, for varying length of stroke of the pump piston, and a control means, responsive to the velocity of the wind to operate the lever means to vary the length of stroke and hence the effective displacement of the pump in accordance with available wind energy, with the control means having a sensing member separate from the windmill disposed in the wind and displaceable thereby in accordance with wind velocity.
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Tactile Sensors for Palm-Size Crawling Robots
2014-05-01
lamination and laser cutting . For the sensor array discussed in this report, the hairs have an average normal sensitivity of approximately 0.8 grams/hair, but...Adhesive (M) Hair Mounting Layer. For visualization purposes, layers I and M are shown with laser - cut features that are actually formed after...The levers are then partially freed from the structure via laser - cutting . The levers are left partly connected at this point so that the hairs (L) can
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ERIC Educational Resources Information Center
Alvarado, Patricio R.; Montalvo, Luis
This is the second book in a five-book physical science series on simple machines. The books are designed for Spanish-speaking junior high school students. By suggesting experiments and posing questions concerning drawings in the book which illustrate the scientific principles, this book explains the workings of three types of levers. Resistance…
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1975-08-09
others, both orally and in writing. - Richard C. LeVere Johns - Manville Denver, Colorado 18 p»w>.^wammMiim<^*ji!wi»i; w mra’i&JifAt. 1...communicate with others, both orally and in writing. Richard C. LeVere Johns - Manville Denver, Colorado Research - research is not con^lete until the
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Geometrical analysis of an optical fiber bundle displacement sensor
NASA Astrophysics Data System (ADS)
Shimamoto, Atsushi; Tanaka, Kohichi
1996-12-01
The performance of a multifiber optical lever was geometrically analyzed by extending the Cook and Hamm model [Appl. Opt. 34, 5854-5860 (1995)] for a basic seven-fiber optical lever. The generalized relationships between sensitivity and the displacement detection limit to the fiber core radius, illumination irradiance, and coupling angle were obtained by analyses of three various types of light source, i.e., a parallel beam light source, an infinite plane light source, and a point light source. The analysis of the point light source was confirmed by a measurement that used the light source of a light-emitting diode. The sensitivity of the fiber-optic lever is inversely proportional to the fiber core radius, whereas the receiving light power is proportional to the number of illuminating and receiving fibers. Thus, the bundling of the finer fiber with the larger number of illuminating and receiving fibers is more effective for improving sensitivity and the displacement detection limit.
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Mounting clips for panel installation
DOE Office of Scientific and Technical Information (OSTI.GOV)
Cavieres, Andres; Al-Haddad, Tristan; Goodman, Joseph
2017-02-14
An exemplary mounting clip for removably attaching panels to a supporting structure comprises a base, spring locking clips, a lateral flange, a lever flange, and a spring bonding pad. The spring locking clips extend upwardly from the base. The lateral flange extends upwardly from a first side of the base. The lateral flange comprises a slot having an opening configured to receive at least a portion of one of the one or more panels. The lever flange extends outwardly from the lateral flange. The spring bonding flange extends downwardly from the lever flange. At least a portion of the firstmore » spring bonding flange comprises a serrated edge for gouging at least a portion of the one or more panels when the one or more panels are attached to the mounting clip to electrically and mechanically couple the one or more panels to the mounting clip.« less
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Calibration Procedures in Mid Format Camera Setups
NASA Astrophysics Data System (ADS)
Pivnicka, F.; Kemper, G.; Geissler, S.
2012-07-01
A growing number of mid-format cameras are used for aerial surveying projects. To achieve a reliable and geometrically precise result also in the photogrammetric workflow, awareness on the sensitive parts is important. The use of direct referencing systems (GPS/IMU), the mounting on a stabilizing camera platform and the specific values of the mid format camera make a professional setup with various calibration and misalignment operations necessary. An important part is to have a proper camera calibration. Using aerial images over a well designed test field with 3D structures and/or different flight altitudes enable the determination of calibration values in Bingo software. It will be demonstrated how such a calibration can be performed. The direct referencing device must be mounted in a solid and reliable way to the camera. Beside the mechanical work especially in mounting the camera beside the IMU, 2 lever arms have to be measured in mm accuracy. Important are the lever arms from the GPS Antenna to the IMU's calibrated centre and also the lever arm from the IMU centre to the Camera projection centre. In fact, the measurement with a total station is not a difficult task but the definition of the right centres and the need for using rotation matrices can cause serious accuracy problems. The benefit of small and medium format cameras is that also smaller aircrafts can be used. Like that, a gyro bases stabilized platform is recommended. This causes, that the IMU must be mounted beside the camera on the stabilizer. The advantage is, that the IMU can be used to control the platform, the problematic thing is, that the IMU to GPS antenna lever arm is floating. In fact we have to deal with an additional data stream, the values of the movement of the stabiliser to correct the floating lever arm distances. If the post-processing of the GPS-IMU data by taking the floating levers into account, delivers an expected result, the lever arms between IMU and camera can be applied. However, there is a misalignment (bore side angle) that must be evaluated by photogrammetric process using advanced tools e.g. in Bingo. Once, all these parameters have been determined, the system is capable for projects without or with only a few ground control points. But which effect has the photogrammetric process when directly applying the achieved direct orientation values compared with an AT based on a proper tiepoint matching? The paper aims to show the steps to be done by potential users and gives a kind of quality estimation about the importance and quality influence of the various calibration and adjustment steps.
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Hypothalamic self-stimulation and stimulation escape in relation to feeding and mating.
Hoebel, B G
1979-10-01
This review begins with James Olds' discovery that self-stimulation at various brain sites can be influenced by food intake or androgen treatment. It then describes our research designed to reveal the functional significance of self-stimulation. The evidence suggests that lateral hypothalamic self-stimulation is controlled by many of the same factors that control feeding. We believe this control is exerted by at least two neural mechanisms. One is the classical, medial hypothalamic satiety system. Another is an adrenergic system ascending from the midbrain to the lateral hypothalamus. Damage to either one can disinhibit self-stimulation and feeding, thus contributing to obesity. Some of our studies use rats with two electrodes, one that induces feeding and one that induces mating. There are two response levers in the test cage, one for self-stimulation and one for escape from automatic stimulation. With the feeding electrode, rats self-stimulated less and escaped more after a meal than before. The same shift occurred after an anorectic dose of insulin or the commercial appetite suppressant phenylpropanolamine. With the sex electrode the shift from reward to aversion occurred after ejaculation. The review ends with credit to James Olds for pioneering this line of research into the neuropsychology of reinforcement.
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Opioidergic and dopaminergic modulation of cost/benefit decision-making in Long Evans Rats.
Morales, Ileana; Currie, Paul J; Hackenberg, Timothy D; Pastor, Raúl
2017-10-01
Eating disorders are associated with impaired decision-making and dysfunctional reward-related neurochemistry. The present study examined the potential contributions of dopamine and opioid signaling to these processes using two different decision-making tasks. In one task, Long Evans Rats chose between working for a preferred food (high-carbohydrate banana-flavored sucrose pellets) by lever pressing on a progressive-ratio schedule of reinforcement vs. obtaining less preferred laboratory chow that was concurrently available. In a second (effort-free) task, rats chose between the same two reinforcers when they were both available freely. Rats were trained in these tasks before receiving haloperidol (0.00, 0.05, 0.10mg/kg, intraperitoneally (i.p.)) or naloxone (0.0, 1.5, 3.0mg/kg, i.p.). In the first task, haloperidol decreased breakpoint, lever presses, number of reinforcers earned, and increased chow intake, whereas naloxone decreased breakpoint and number of reinforcers earned but had no effect on chow consumption. In the effort-free task, haloperidol reduced intakes of both foods without affecting preference, whereas naloxone selectively reduced the consumption of banana-pellets. The present findings support converging evidence suggesting that DA signaling affects processes more closely related to appetitive motivation, leaving other components of motivation unchanged. By contrast, opioid signaling appears to mediate aspects of hedonic feeding by selectively altering intakes of highly palatable foods. For preferred foods, both appetitive and consummatory aspects of food intake were altered by opioid receptor antagonism. Our findings argue against a general suppression of appetite by either compound, as appetite manipulations have been shown to unselectively alter intakes of both types of food regardless of the task employed. Copyright © 2017 Elsevier Inc. All rights reserved.
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2017-10-01
agricultural tractors used on SPoT (Case Corporation and Caterpillar). (Adapted from Lever and Thur 2014.) ................. 2 2 Map showing the 1600...traversed for the first time in 2005 as a proof-of-concept, using a combination of several commercial rubber-tracked agricultural tractors (Caterpillar...traverse route. Inset shows two rubber-tracked, agricultural tractors used on SPoT (Case Corporation and Caterpillar). (Adapted from Lever and Thur 2014
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Isolating the incentive salience of reward-associated stimuli: value, choice, and persistence
Chow, Jonathan J.
2015-01-01
Sign- and goal-tracking are differentially associated with drug abuse-related behavior. Recently, it has been hypothesized that sign- and goal-tracking behavior are mediated by different neurobehavioral valuation systems, including differential incentive salience attribution. Herein, we used different conditioned stimuli to preferentially elicit different response types to study the different incentive valuation characteristics of stimuli associated with sign- and goal-tracking within individuals. The results demonstrate that all stimuli used were equally effective conditioned stimuli; however, only a lever stimulus associated with sign-tracking behavior served as a robust conditioned reinforcer and was preferred over a tone associated with goal-tracking. Moreover, the incentive value attributed to the lever stimulus was capable of promoting suboptimal choice, leading to a significant reduction in reinforcers (food) earned. Furthermore, sign-tracking to a lever was more persistent than goal-tracking to a tone under omission and extinction contingencies. Finally, a conditional discrimination procedure demonstrated that sign-tracking to a lever and goal-tracking to a tone were dependent on learned stimulus–reinforcer relations. Collectively, these results suggest that the different neurobehavioral valuation processes proposed to govern sign- and goal-tracking behavior are independent but parallel processes within individuals. Examining these systems within individuals will provide a better understanding of how one system comes to dominate stimulus–reward learning, thus leading to the differential role these systems play in abuse-related behavior. PMID:25593298
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Rotteveel, Mark; Gierholz, Alexander; Koch, Gijs; van Aalst, Cherelle; Pinto, Yair; Matzke, Dora; Steingroever, Helen; Verhagen, Josine; Beek, Titia F.; Selker, Ravi; Sasiadek, Adam; Wagenmakers, Eric-Jan
2015-01-01
Within the literature on emotion and behavioral action, studies on approach-avoidance take up a prominent place. Several experimental paradigms feature successful conceptual replications but many original studies have not yet been replicated directly. We present such a direct replication attempt of two seminal experiments originally conducted by Chen and Bargh (1999). In their first experiment, participants affectively evaluated attitude objects by pulling or pushing a lever. Participants who had to pull the lever with positively valenced attitude objects and push the lever with negatively valenced attitude objects (i.e., congruent instruction) did so faster than participants who had to follow the reverse (i.e., incongruent) instruction. In Chen and Bargh's second experiment, the explicit evaluative instructions were absent and participants merely responded to the attitude objects by either always pushing or always pulling the lever. Similar results were obtained as in Experiment 1. Based on these findings, Chen and Bargh concluded that (1) attitude objects are evaluated automatically; and (2) attitude objects automatically trigger a behavioral tendency to approach or avoid. We attempted to replicate both experiments and failed to find the effects reported by Chen and Bargh as indicated by our pre-registered Bayesian data analyses; nevertheless, the evidence in favor of the null hypotheses was only anecdotal, and definitive conclusions await further study. PMID:25883572
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[Relationship of the elderly nutrition knowledge and their education level in Nanjing].
Liu, Chen; Su, Yamei; Jin, Bangquan
2013-07-01
To study the relationship of the elderly nutrition knowledge, eating behavior and BMI status with their education level. A questionnaire was designed to investigate 1367 elders in 26 nursing homes and communities of Nanjing. Accoording to the education lever, elders nutrition knowledge in college and high school was more than that in middle and primary school, significantly (P < 0.05, P < 0.01). Elders in college and high school groups could obtain much more informations via diversification, such as book, journal or magazine, interpersonal communication and TV or radio. While, 50% elders in lower education groups (middle and primary school) usually watch TV or lisen to the radio get knowledge. The higher education level, the higher income for elders. For this reason, their dietary structure and eating behavior were tending to be reasonable. Compared with the education lever, age and BMI, the effect of age on BMI was more than education lever. The ratio of weight loss and obesity in 75 years old was clearly increased, their nutrition supplment needs more care. elderly education lever was a key factor on their nutrition knowledge and eating behavior (P = 0.00). In college and high school groups, elders nutrition knowledge and income were better than lower education level. However, the age was closed relative to BMI. When elders was over 75 years old, their body weight tend to loss or over and need more nutritional attention.
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Steinmo, Siri H; Michie, Susan; Fuller, Christopher; Stanley, Sarah; Stapleton, Caitriona; Stone, Sheldon P
2016-02-03
Sepsis has a mortality rate of 40 %, which can be halved if the evidence-based "Sepsis Six" care bundle is implemented within 1 h. UK audit shows low implementation rates. Interventions to improve this have had minimal effects. Quality improvement programmes could be further developed by using theoretical frameworks (Theoretical Domains Framework (TDF)) to modify existing interventions by identifying influences on clinical behaviour and selecting appropriate content. The aim of this study was to illustrate using this process to modify an intervention designed using plan-do-study-act (P-D-S-A) cycles that had achieved partial success in improving Sepsis Six implementation in one hospital. Factors influencing implementation were investigated using the TDF to analyse interviews with 34 health professionals. The nursing team who developed and facilitated the intervention used the data to select modifications using the Behaviour Change Technique (BCT) Taxonomy (v1) and the APEASE criteria: affordability, practicability, effectiveness, acceptability, safety and equity. Five themes were identified as influencing implementation and guided intervention modification. These were:(1) "knowing what to do and why" (TDF domains knowledge, social/professional role and identity); (2) "risks and benefits" (beliefs about consequences), e.g. fear of harming patients through fluid overload acting as a barrier to implementation versus belief in the bundle's effectiveness acting as a lever to implementation; (3) "working together" (social influences, social/professional role and identity), e.g. team collaboration acting as a lever versus doctor/nurse conflict acting as a barrier; (4) "empowerment and support" (beliefs about capabilities, social/professional role and identity, behavioural regulation, social influences), e.g. involving staff in intervention development acting as a lever versus lack of confidence to challenge colleagues' decisions not to implement acting as a barrier; (5) "staffing levels" (environmental context and resources), e.g. shortages of doctors at night preventing implementation. The modified intervention included six new BCTs and consisted of two additional components (Sepsis Six training for the Hospital at Night Co-ordinator; a partnership agreement endorsing engagement of all clinical staff and permitting collegial challenge) and modifications to two existing components (staff education sessions; documents and materials). This work demonstrates the feasibility of the TDF and BCT Taxonomy (v1) for developing an existing quality improvement intervention. The tools are compatible with the pragmatic P-D-S-A cycle approach generally used in quality improvement work.
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Rodd, Zachary A; Bell, Richard L; Oster, Scott M; Toalston, Jamie E; Pommer, Tylene J; McBride, William J; Murphy, James M
2010-05-01
Several studies indicated the involvement of serotonin-3 ([5-hydroxy tryptamine] 5-HT(3)) receptors in regulating alcohol-drinking behavior. The objective of this study was to determine the involvement of 5-HT(3) receptors within the ventral tegmental area (VTA) in regulating ethanol self-administration by alcohol-preferring (P) rats. Standard two-lever operant chambers (Coulbourn Instruments, Allentown, PA) were used to examine the effects of seven consecutive bilateral microinfusions of ICS 205-930 (ICS), a 5-HT(3) receptor antagonist, directly into the posterior VTA on the acquisition and maintenance of 15% (vol/vol) ethanol self-administration. P rats readily acquired ethanol self-administration by the fourth session. The three highest doses (0.125, 0.25, and 1.25 microg) of ICS prevented acquisition of ethanol self-administration. During the acquisition postinjection period, all rats treated with ICS demonstrated higher responding on the ethanol lever, with the highest dose producing the greatest effect. In contrast, during the maintenance phase, the three highest doses (0.75, 1.0, and 1.25 microg) of ICS significantly increased responding on the ethanol lever; after the 7-day dosing regimen, responding on the ethanol lever returned to control levels. Microinfusion of ICS into the posterior VTA did not alter the low responding on the water lever and did not alter saccharin (0.0125% wt/v) self-administration. Microinfusion of ICS into the anterior VTA did not alter ethanol self-administration. Overall, the results of this study suggest that 5-HT(3) receptors in the posterior VTA of the P rat may be involved in regulating ethanol self-administration. In addition, chronic operant ethanol self-administration and/or repeated treatments with a 5-HT(3) receptor antagonist may alter neuronal circuitry within the posterior VTA. 2010 Elsevier Inc. All rights reserved.
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Coupling of Lever Arm Swing and Biased Brownian Motion in Actomyosin
Nie, Qing-Miao; Togashi, Akio; Sasaki, Takeshi N.; Takano, Mitsunori; Sasai, Masaki; Terada, Tomoki P.
2014-01-01
An important unresolved problem associated with actomyosin motors is the role of Brownian motion in the process of force generation. On the basis of structural observations of myosins and actins, the widely held lever-arm hypothesis has been proposed, in which proteins are assumed to show sequential structural changes among observed and hypothesized structures to exert mechanical force. An alternative hypothesis, the Brownian motion hypothesis, has been supported by single-molecule experiments and emphasizes more on the roles of fluctuating protein movement. In this study, we address the long-standing controversy between the lever-arm hypothesis and the Brownian motion hypothesis through in silico observations of an actomyosin system. We study a system composed of myosin II and actin filament by calculating free-energy landscapes of actin-myosin interactions using the molecular dynamics method and by simulating transitions among dynamically changing free-energy landscapes using the Monte Carlo method. The results obtained by this combined multi-scale calculation show that myosin with inorganic phosphate (Pi) and ADP weakly binds to actin and that after releasing Pi and ADP, myosin moves along the actin filament toward the strong-binding site by exhibiting the biased Brownian motion, a behavior consistent with the observed single-molecular behavior of myosin. Conformational flexibility of loops at the actin-interface of myosin and the N-terminus of actin subunit is necessary for the distinct bias in the Brownian motion. Both the 5.5–11 nm displacement due to the biased Brownian motion and the 3–5 nm displacement due to lever-arm swing contribute to the net displacement of myosin. The calculated results further suggest that the recovery stroke of the lever arm plays an important role in enhancing the displacement of myosin through multiple cycles of ATP hydrolysis, suggesting a unified movement mechanism for various members of the myosin family. PMID:24762409
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Coupling of lever arm swing and biased Brownian motion in actomyosin.
Nie, Qing-Miao; Togashi, Akio; Sasaki, Takeshi N; Takano, Mitsunori; Sasai, Masaki; Terada, Tomoki P
2014-04-01
An important unresolved problem associated with actomyosin motors is the role of Brownian motion in the process of force generation. On the basis of structural observations of myosins and actins, the widely held lever-arm hypothesis has been proposed, in which proteins are assumed to show sequential structural changes among observed and hypothesized structures to exert mechanical force. An alternative hypothesis, the Brownian motion hypothesis, has been supported by single-molecule experiments and emphasizes more on the roles of fluctuating protein movement. In this study, we address the long-standing controversy between the lever-arm hypothesis and the Brownian motion hypothesis through in silico observations of an actomyosin system. We study a system composed of myosin II and actin filament by calculating free-energy landscapes of actin-myosin interactions using the molecular dynamics method and by simulating transitions among dynamically changing free-energy landscapes using the Monte Carlo method. The results obtained by this combined multi-scale calculation show that myosin with inorganic phosphate (Pi) and ADP weakly binds to actin and that after releasing Pi and ADP, myosin moves along the actin filament toward the strong-binding site by exhibiting the biased Brownian motion, a behavior consistent with the observed single-molecular behavior of myosin. Conformational flexibility of loops at the actin-interface of myosin and the N-terminus of actin subunit is necessary for the distinct bias in the Brownian motion. Both the 5.5-11 nm displacement due to the biased Brownian motion and the 3-5 nm displacement due to lever-arm swing contribute to the net displacement of myosin. The calculated results further suggest that the recovery stroke of the lever arm plays an important role in enhancing the displacement of myosin through multiple cycles of ATP hydrolysis, suggesting a unified movement mechanism for various members of the myosin family.
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Sanabria, Federico; Killeen, Peter R
2008-01-01
Background The inability to inhibit reinforced responses is a defining feature of ADHD associated with impulsivity. The Spontaneously Hypertensive Rat (SHR) has been extolled as an animal model of ADHD, but there is no clear experimental evidence of inhibition deficits in SHR. Attempts to demonstrate these deficits may have suffered from methodological and analytical limitations. Methods We provide a rationale for using two complementary response-withholding tasks to doubly dissociate impulsivity from motivational and motor processes. In the lever-holding task (LHT), continual lever depression was required for a minimum interval. Under a differential reinforcement of low rates schedule (DRL), a minimum interval was required between lever presses. Both tasks were studied using SHR and two normotensive control strains, Wistar-Kyoto (WKY) and Long Evans (LE), over an overlapping range of intervals (1 – 5 s for LHT and 5 – 60 s for DRL). Lever-holding and DRL performance was characterized as the output of a mixture of two processes, timing and iterative random responding; we call this account of response inhibition the Temporal Regulation (TR) model. In the context of TR, impulsivity was defined as a bias toward premature termination of the timed intervals. Results The TR model provided an accurate description of LHT and DRL performance. On the basis of TR parameter estimates, SHRs were more impulsive than LE rats across tasks and target times. WKY rats produced substantially shorter timed responses in the lever-holding task than in DRL, suggesting a motivational or motor deficit. The precision of timing by SHR, as measured by the variance of their timed intervals, was excellent, flouting expectations from ADHD research. Conclusion This research validates the TR model of response inhibition and supports SHR as an animal model of ADHD-related impulsivity. It indicates, however, that SHR's impulse-control deficit is not caused by imprecise timing. The use of ad hoc impulsivity metrics and of WKY as control strain for SHR impulsivity are called into question. PMID:18261220
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Turbine Engine Control Synthesis. Volume 1. Optimal Controller Synthesis and Demonstration
1975-03-01
Nomenclature (Continued) Symbol Deseription M Matrix (of Table 12) M Mach number N Rotational speed, rpm N ’ Nonlinear rotational speed, rpm P Power lever... P Pressure, N /m 2; bfh/ft 2 PLA Power lever angle PR = PT3/PT2 Pressure ratio ( P Power, ft-lbf/sec Q Matrix (of Table 30) R Universal gas constant, 53...function, i = 1, 2, 3, ... in Inlet n Stage number designation out Outlet p Variable associated with particle s Static condition _se Static condition
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2008-02-01
liabilities (e.g., accounts payable). This ratio can be compared to the firm’s weighted average cost of capital ( WACC ). WACC is the cost of debt plus the cost...RatioCost of Debt Marginal Tax Rate Risk-Free Rate Cost of Equity Risk Premium Industry Beta WACC Technical Risk CPFF/CPAF …. FFP/ MYP - Contract Choice...estimates the levered WACC as the discount rate, and finally calculates the NPV of the contract. Specific model input includes profit policy levers
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Lomanowska, Anna M; Kraemer, Gary W
2014-09-01
Early-life social adversity, such as child neglect and institutionalized rearing, is associated with later-life difficulties of inhibitory control that may reflect altered attribution of salience to external stimuli. Studies in rats demonstrate that early-life social deprivation results in enhanced responsiveness to reward stimuli and conditioned reward cues. This study examined whether these effects are related to fundamental changes in appetitive conditioning processes involving instrumental goal-directed and habitual responding for food reward. Rats were reared either by the mother (maternal rearing; MR) or in complete isolation from the mother and litter (artificial rearing; AR) and tested as adults in two appetitive conditioning tasks. AR and MR rats did not differ in the amount of goal-directed effort they exerted to obtain food reward on progressive ratio schedules of reinforcement. AR and MR rats also did not differ in the shift from goal-directed to habitual responding on a random interval schedule and they were equally sensitive to changes in reward value. The major difference between AR and MR rats was that AR rats exhibited more non-instrumental responses (empty food magazine entries, ineffective lever presses). Thus, early-life social deprivation of rats through AR affects the expression of unreinforced extraneous behaviors when motivational requirements are high, but does not affect conditioned goal-directed and habitual responding to reward. The findings have implications for understanding what aspects of responsiveness to external stimuli may be selectively affected in disorders of inhibition associated with early-life social adversity. Copyright © 2014 Elsevier B.V. All rights reserved.
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Hayrapetyan, Volodya; Castro, Stephen; Sukharnikova, Tatyana; Yu, Chunxiu; Cao, Xinyu; Jiang, Yong-Hui; Yin, Henry H.
2018-01-01
Angelman syndrome (AS) is a neurodevelopmental disorder characterized by mental retardation and impaired speech. Because patients with this disorder often exhibit motor tremor and stereotypical behaviors, which are associated with basal ganglia pathology, we hypothesized that AS is accompanied by abnormal functioning of the striatum, the input nucleus of the basal ganglia. Using mutant mice with maternal deficiency of AS E6-AP ubiquitin protein ligase Ube3a (Ube3am−/p+), we assessed the effects of Ube3a deficiency on instrumental conditioning, a striatum-dependent task. We used whole-cell patch-clamp recording to measure glutamatergic transmission in the dorsomedial striatum (DMS) and dorsolateral striatum (DLS). Ube3am−/p+ mice were severely impaired in initial acquisition of lever pressing. Whereas the lever pressing of wild-type controls was reduced by outcome devaluation and instrumental contingency reversal, the performance of Ube3am−/p+ mice were more habitual, impervious to changes in outcome value and action–outcome contingency. In the DMS, but not the DLS, Ube3am−/p+ mice showed reduced amplitude and frequency of miniature excitatory postsynaptic currents. These results show for the first time a selective deficit in instrumental conditioning in the Ube3a deficient mouse model, and suggest a specific impairment in glutmatergic transmission in the associative corticostriatal circuit in AS. PMID:24329862
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Tedford, Stephanie E; Persons, Amanda L; Napier, T Celeste
2015-01-01
Dysregulated dopamine transmission in striatal circuitry is associated with impulsivity. The current study evaluated the influence of dopaminergic inputs to the dorsolateral striatum on impulsive choice, one aspect of impulsive behavior. We implemented an operant task that measures impulsive choice in rats via delay discounting wherein intracranial self-stimulation (ICSS) was used as the positive reinforcer. To do so, rats were anesthetized to allow implanting of a stimulating electrode within the lateral hypothalamus of one hemisphere and bilateral dorsal striatal injections of the dopaminergic toxin, 6-OHDA (lesioned) or its vehicle (sham). Following recovery, rats were trained in a delay discounting task wherein they selected between a small ICSS current presented immediately after lever pressing, and a large ICSS current presented following a 0 to 15 s delay upon pressing the alternate lever. Task acquisition and reinforcer discrimination were similar for lesioned and sham rats. All rats exhibited an initial preference for the large reinforcer, and as the delay was increased, preference for the large reinforcer was decreased indicating that the subjective value of the large reinforcer was discounted as a function of delay time. However, this discounting effect was significantly enhanced in lesioned rats for the longer delays. These data reveal a contribution of dopaminergic inputs to the dorsolateral striatum on impulsive choice behavior, and provide new insights into neural substrates underlying discounting behaviors.
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Cha, Biblia S; Lawrence, Rachel I; Bliss, Jesse C; Wells, Kenneth B; Chandra, Anita; Eisenman, David P
2016-12-01
Local health departments (LHDs) have little guidance for operationalizing community resilience (CR). We explored how community coalitions responded to 4 CR levers (education, engagement, partnerships, and community self-sufficiency) during the first planning year of the Los Angeles County Community Disaster Resilience (LACCDR) Project. Sixteen communities were selected and randomly assigned to the experimental CR group or the control preparedness group. Eight CR coalitions met monthly to plan CR-building activities or to receive CR training from a public health nurse. Trained observers documented the coalitions' understanding and application of CR at each meeting. Qualitative content analysis was used to analyze structured observation reports around the 4 levers. Analysis of 41 reports suggested that coalitions underwent a process of learning about and applying CR concepts in the planning year. Groups resonated with ideas of education, community self-sufficiency, and engagement, but increasing partnerships was challenging. LHDs can support coalitions by anticipating the time necessary to understand CR and by facilitating engagement. Understanding the issues that emerge in the early phases of planning and implementing CR-building activities is critical. LHDs can use the experience of the LACCDR Project's planning year as a guide to navigate challenges and issues that emerge as they operationalize the CR model. (Disaster Med Public Health Preparedness. 2016;10:812-821).
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Tedford, Stephanie E.; Persons, Amanda L.; Napier, T. Celeste
2015-01-01
Dysregulated dopamine transmission in striatal circuitry is associated with impulsivity. The current study evaluated the influence of dopaminergic inputs to the dorsolateral striatum on impulsive choice, one aspect of impulsive behavior. We implemented an operant task that measures impulsive choice in rats via delay discounting wherein intracranial self-stimulation (ICSS) was used as the positive reinforcer. To do so, rats were anesthetized to allow implanting of a stimulating electrode within the lateral hypothalamus of one hemisphere and bilateral dorsal striatal injections of the dopaminergic toxin, 6-OHDA (lesioned) or its vehicle (sham). Following recovery, rats were trained in a delay discounting task wherein they selected between a small ICSS current presented immediately after lever pressing, and a large ICSS current presented following a 0 to 15s delay upon pressing the alternate lever. Task acquisition and reinforcer discrimination were similar for lesioned and sham rats. All rats exhibited an initial preference for the large reinforcer, and as the delay was increased, preference for the large reinforcer was decreased indicating that the subjective value of the large reinforcer was discounted as a function of delay time. However, this discounting effect was significantly enhanced in lesioned rats for the longer delays. These data reveal a contribution of dopaminergic inputs to the dorsolateral striatum on impulsive choice behavior, and provide new insights into neural substrates underlying discounting behaviors. PMID:25927685
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Effects of phencyclidine, secobarbital and diazepam on eye tracking in rhesus monkeys.
Ando, K; Johanson, C E; Levy, D L; Yasillo, N J; Holzman, P S; Schuster, C R
1983-01-01
Rhesus monkeys were trained to track a moving disk using a procedure in which responses on a lever were reinforced with water delivery only when the disk, oscillating in a horizontal plane on a screen at a frequency of 0.4 Hz in a visual angle of 20 degrees, dimmed for a brief period. Pursuit eye movements were recorded by electrooculography (EOG). IM phencyclidine, secobarbital, and diazepam injections decreased the number of reinforced lever presses in a dose-related manner. Both secobarbital and diazepam produced episodic jerky-pursuit eye movements, while phencyclidine had no consistent effects on eye movements. Lever pressing was disrupted at doses which had little effect on the quality of smooth-pursuit eye movements in some monkeys. This separation was particularly pronounced with diazepam. The similarities of the drug effects on smooth-pursuit eye movements between the present study and human studies indicate that the present method using rhesus monkeys may be useful for predicting drug effects on eye tracking and oculomotor function in humans.
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Reinstatement of MDMA (ecstasy) seeking by exposure to discrete drug-conditioned cues
Ball, Kevin T.; Walsh, Kelly M.; Rebec, George V.
2007-01-01
The widely used recreational drug MDMA (ecstasy) supports self-administration in animals, but it is not known whether MDMA-associated cues are able to reinstate drug seeking in a relapse model of drug addiction. To assess this possibility, drug-naïve rats were trained to press a lever for MDMA infusions (0.30 mg/kg/infusion, i.v.) paired with a compound cue (light and tone) in daily 2 hr sessions. Responding was reinforced contingent on a modified fixed-ratio 5 schedule of reinforcement. Conditioned cue-induced reinstatement tests were conducted after lever pressing was extinguished in the absence of MDMA and the conditioned cues. Conditioned cues reinstated lever pressing after extinction, and the magnitude of reinstatement was positively correlated with the level of responding during MDMA self-administration. These results show for the first time that conditioned cues can trigger reinstatement of MDMA-seeking behavior in rats, and that individual differences in the pattern of MDMA self-administration can predict the magnitude of reinstatement responding. PMID:17602729
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Myosin V is a biological Brownian machine.
Fujita, Keisuke; Iwaki, Mitsuhiro
2014-01-01
Myosin V is a vesicle transporter that unidirectionally walks along cytoskeletal actin filaments by converting the chemical energy of ATP into mechanical work. Recently, it was found that myosin V force generation is a composition of two processes: a lever-arm swing, which involves a conformational change in the myosin molecule, and a Brownian search-and-catch, which involves a diffusive "search" by the motor domain that is followed by an asymmetric "catch" in the forward actin target such that Brownian motion is rectified. Here we developed a system that combines optical tweezers with DNA nano-material to show that the Brownian search-and-catch mechanism is the energetically dominant process at near stall force, providing 13 kBT of work compared to just 3 kBT by the lever-arm swing. Our result significantly reconsiders the lever-arm swinging model, which assumes the swing dominantly produces work (>10 kBT), and sheds light on the Brownian search-and-catch as a driving process.
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Myosin V is a biological Brownian machine
Fujita, Keisuke; Iwaki, Mitsuhiro
2014-01-01
Myosin V is a vesicle transporter that unidirectionally walks along cytoskeletal actin filaments by converting the chemical energy of ATP into mechanical work. Recently, it was found that myosin V force generation is a composition of two processes: a lever-arm swing, which involves a conformational change in the myosin molecule, and a Brownian search-and-catch, which involves a diffusive “search” by the motor domain that is followed by an asymmetric “catch” in the forward actin target such that Brownian motion is rectified. Here we developed a system that combines optical tweezers with DNA nano-material to show that the Brownian search-and-catch mechanism is the energetically dominant process at near stall force, providing 13 kBT of work compared to just 3 kBT by the lever-arm swing. Our result significantly reconsiders the lever-arm swinging model, which assumes the swing dominantly produces work (>10 kBT), and sheds light on the Brownian search-and-catch as a driving process. PMID:27493501
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The post-rigor structure of myosin VI and implications for the recovery stroke
Ménétrey, Julie; Llinas, Paola; Cicolari, Jérome; Squires, Gaëlle; Liu, Xiaoyan; Li, Anna; Sweeney, H Lee; Houdusse, Anne
2008-01-01
Myosin VI has an unexpectedly large swing of its lever arm (powerstroke) that optimizes its unique reverse direction movement. The basis for this is an unprecedented rearrangement of the subdomain to which the lever arm is attached, referred to as the converter. It is unclear at what point(s) in the myosin VI ATPase cycle rearrangements in the converter occur, and how this would effect lever arm position. We solved the structure of myosin VI with an ATP analogue (ADP.BeF3) bound in its nucleotide-binding pocket. The structure reveals that no rearrangement in the converter occur upon ATP binding. Based on previously solved myosin structures, our structure suggests that no reversal of the powerstroke occurs during detachment of myosin VI from actin. The structure also reveals novel features of the myosin VI motor that may be important in maintaining the converter conformation during detachment from actin, and other features that may promote rapid rearrangements in the structure following actin detachment that enable hydrolysis of ATP. PMID:18046460
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Tompa, Emile; Kalcevich, Christina; Foley, Michael; McLeod, Chris; Hogg-Johnson, Sheilah; Cullen, Kim; MacEachen, Ellen; Mahood, Quenby; Irvin, Emma
2016-11-01
We aimed to determine the strength of evidence on the effectiveness of legislative and regulatory policy levers in creating incentives for organizations to improve occupational health and safety processes and outcomes. A systematic review was undertaken to assess the strength of evidence on the effectiveness of specific policy levers using a "best-evidence" synthesis approach. A structured literature search identified 11,947 citations from 13 peer-reviewed literature databases. Forty-three studies were retained for synthesis. Strong evidence was identified for three out of nine clusters. There is strong evidence that several OHS policy levers are effective in terms of reducing injuries and/or increasing compliance with legislation. This study adds to the evidence on OHS regulatory effectiveness from an earlier review. In addition to new evidence supporting previous study findings, it included new categories of evidence-compliance as an outcome, nature of enforcement, awareness campaigns, and smoke-free workplace legislation. Am. J. Ind. Med. 59:919-933, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.
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Behavioral effects of delayed timeouts from reinforcement.
Byrne, Tom; Poling, Alan
2017-03-01
Timeouts are sometimes used in applied settings to reduce target responses, and in some circumstances delays are unavoidably imposed between the onset of a timeout and the offset of the response that produces it. The present study examined the effects of signaled and unsignaled timeouts in rats exposed to concurrent fixed-ratio 1 fixed-ratio 1 schedules of food delivery, where each response on one lever, the location of which changed across conditions, produced both food and a delayed 10-s timeout. Delays of 0 to 38 s were examined. Delayed timeouts often, but not always, substantially reduced the number of responses emitted on the lever that produced timeouts relative to the number emitted on the lever that did not produce timeouts. In general, greater sensitivity was observed to delayed timeouts when they were signaled. These results demonstrate that delayed timeouts, like other delayed consequences, can affect behavior, albeit less strongly than immediate consequences. © 2017 Society for the Experimental Analysis of Behavior.
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Directional control-response relationships for mining equipment.
Burgess-Limerick, R; Krupenia, V; Wallis, G; Pratim-Bannerjee, A; Steiner, L
2010-06-01
A variety of directional control-response relationships are currently found in mining equipment. Two experiments were conducted in a virtual environment to determine optimal direction control-response relationships in a wide variety of circumstances. Direction errors were measured as a function of control orientation (horizontal or vertical), location (left, front, right) and directional control-response relationships. The results confirm that the principles of consistent direction and visual field compatibility are applicable to the majority of situations. An exception is that fewer direction errors were observed when an upward movement of a horizontal lever or movement of a vertical lever away from the participants caused extension (lengthening) of the controlled device, regardless of whether the direction of movement of the control is consistent with the direction in which the extension occurs. Further, both the control of slew by horizontally oriented controls and the control of device movements in a frontal plane by the perpendicular movements of vertical levers were associated with relatively high rates of directional errors, regardless of the directional control-response relationship, and these situations should be avoided. STATEMENT OF RELEVANCE: The results are particularly applicable to the design of mining equipment such as drilling and bolting machines, and have been incorporated into MDG35.1 Guideline for bolting & drilling plant in mines (Industry & Investment NSW, 2010). The results are also relevant to the design of any equipment where vertical or horizontal levers are used to control the movement of equipment appendages, e.g. cranes mounted to mobile equipment and the like.
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Fredman, Tamar; Whiten, Andrew
2008-04-01
Studies of wild capuchins suggest an important role for social learning, but experiments with captive subjects have generally not supported this. Here we report social learning in two quite different populations of capuchin monkeys (Cebus apella). In experiment 1, human-raised monkeys observed a familiar human model open a foraging box using a tool in one of two alternative ways: levering versus poking. In experiment 2, mother-raised monkeys viewed similar techniques demonstrated by monkey models. A control group in each population saw no model. In both experiments, independent coders detected which technique experimental subjects had seen, thus confirming social learning. Further analyses examined fidelity of copying at three levels of resolution. The human-raised monkeys exhibited fidelity at the highest level, the specific tool use technique witnessed. The lever technique was seen only in monkeys exposed to a levering model, by contrast with controls and those witnessing poke. Mother-reared monkeys instead typically ignored the tool and exhibited fidelity at a lower level, tending only to re-create whichever result the model had achieved by either levering or poking. Nevertheless this level of social learning was associated with significantly greater levels of success in monkeys witnessing a model than in controls, an effect absent in the human-reared population. Results in both populations are consistent with a process of canalization of the repertoire in the direction of the approach witnessed, producing a narrower, socially shaped behavioural profile than among controls who saw no model.
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Schiller, Peter H; Kwak, Michelle C; Slocum, Warren M
2012-08-01
This study examined how effectively visual and auditory cues can be integrated in the brain for the generation of motor responses. The latencies with which saccadic eye movements are produced in humans and monkeys form, under certain conditions, a bimodal distribution, the first mode of which has been termed express saccades. In humans, a much higher percentage of express saccades is generated when both visual and auditory cues are provided compared with the single presentation of these cues [H. C. Hughes et al. (1994) J. Exp. Psychol. Hum. Percept. Perform., 20, 131-153]. In this study, we addressed two questions: first, do monkeys also integrate visual and auditory cues for express saccade generation as do humans and second, does such integration take place in humans when, instead of eye movements, the task is to press levers with fingers? Our results show that (i) in monkeys, as in humans, the combined visual and auditory cues generate a much higher percentage of express saccades than do singly presented cues and (ii) the latencies with which levers are pressed by humans are shorter when both visual and auditory cues are provided compared with the presentation of single cues, but the distribution in all cases is unimodal; response latencies in the express range seen in the execution of saccadic eye movements are not obtained with lever pressing. © 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.
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Wheel-running reinforcement in free-feeding and food-deprived rats.
Belke, Terry W; Pierce, W David
2016-03-01
Rats experiencing sessions of 30min free access to wheel running were assigned to ad-lib and food-deprived groups, and given additional sessions of free wheel activity. Subsequently, both ad-lib and deprived rats lever pressed for 60s of wheel running on fixed ratio (FR) 1, variable ratio (VR) 3, VR 5, and VR 10 schedules, and on a response-initiated variable interval (VI) 30s schedule. Finally, the ad-lib rats were switched to food deprivation and the food-deprived rats were switched to free food, as rats continued responding on the response-initiated VI 30-s schedule. Wheel running functioned as reinforcement for both ad-lib and food-deprived rats. Food-deprived rats, however, ran faster and had higher overall lever-pressing rates than free-feeding rats. On the VR schedules, wheel-running rates positively correlated with local and overall lever pressing rates for deprived, but not ad-lib rats. On the response-initiated VI 30s schedule, wheel-running rates and lever-pressing rates changed for ad-lib rats switched to food deprivation, but not for food-deprived rats switched to free-feeding. The overall pattern of results suggested different sources of control for wheel running: intrinsic motivation, contingencies of automatic reinforcement, and food-restricted wheel running. An implication is that generalizations about operant responding for wheel running in food-deprived rats may not extend to wheel running and operant responding of free-feeding animals. Copyright © 2015 Elsevier B.V. All rights reserved.
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Kearns, David N; Gomez-Serrano, Maria A; Weiss, Stanley J; Riley, Anthony L
2006-05-15
Lewis (LEW) and Fischer (F344) rat strains differ on a number of physiological characteristics, such as hypothalamic-pituitary-adrenal (HPA) axis activity, as well as on behavioral tasks, including those that measure impulsivity and drug reward. Since autoshaping, the phenomenon where animals approach and contact reward-paired conditioned stimuli, has been linked to HPA axis functioning, impulsivity and drug taking, the present study compared LEW and F344 rats on the rate of acquisition and performance of the autoshaping response. Rats were trained on an autoshaping procedure where insertions of one retractable lever (CS(+)) were paired response-independently with food, while insertions of another lever (CS(-)) were not paired with food. LEW rats acquired the autoshaping response more rapidly and also performed the autoshaping response at a higher rate than F344 rats. No differences between the strains were observed when rats were trained on a discrimination reversal where the CS(+) and CS(-) levers were reversed or during a negative auto-maintenance phase where CS(+) lever contacts cancelled food delivery. Potential physiological mechanisms that might mediate the present results, including strain differences in HPA axis and monoamine neurotransmitter activity, are discussed. The finding that LEW (as compared to F344 rats) more readily acquire autoshaping and perform more responses is consistent with research indicating that LEW rats behave more impulsively and more readily self-administer drugs of abuse.
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Resurgence of Integrated Behavioral Units
Bachá-Méndez, Gustavo; Reid, Alliston K; Mendoza-Soylovna, Adela
2007-01-01
Two experiments with rats examined the dynamics of well-learned response sequences when reinforcement contingencies were changed. Both experiments contained four phases, each of which reinforced a 2-response sequence of lever presses until responding was stable. The contingencies then were shifted to a new reinforced sequence until responding was again stable. Extinction-induced resurgence of previously reinforced, and then extinguished, heterogeneous response sequences was observed in all subjects in both experiments. These sequences were demonstrated to be integrated behavioral units, controlled by processes acting at the level of the entire sequence. Response-level processes were also simultaneously operative. Errors in sequence production were strongly influenced by the terminal, not the initial, response in the currently reinforced sequence, but not by the previously reinforced sequence. These studies demonstrate that sequence-level and response-level processes can operate simultaneously in integrated behavioral units. Resurgence and the development of integrated behavioral units may be dissociated; thus the observation of one does not necessarily imply the other. PMID:17345948
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Radio frequency reflectometry and charge sensing of a precision placed donor in silicon
DOE Office of Scientific and Technical Information (OSTI.GOV)
Hile, Samuel J., E-mail: samhile@gmail.com; House, Matthew G.; Peretz, Eldad
2015-08-31
We compare charge transitions on a deterministic single P donor in silicon using radio frequency reflectometry measurements with a tunnel coupled reservoir and DC charge sensing using a capacitively coupled single electron transistor (SET). By measuring the conductance through the SET and comparing this with the phase shift of the reflected radio frequency (RF) excitation from the reservoir, we can discriminate between charge transfer within the SET channel and tunneling between the donor and reservoir. The RF measurement allows observation of donor electron transitions at every charge degeneracy point in contrast to the SET conductance signal where charge transitions aremore » only observed at triple points. The tunnel coupled reservoir has the advantage of a large effective lever arm (∼35%), allowing us to independently extract a neutral donor charging energy ∼62 ± 17 meV. These results demonstrate that we can replace three terminal transistors by a single terminal dispersive reservoir, promising for high bandwidth scalable donor control and readout.« less
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Structural basis for drug-induced allosteric changes to human β-cardiac myosin motor activity
Winkelmann, Donald A.; Forgacs, Eva; Miller, Matthew T.; Stock, Ann M.
2015-01-01
Omecamtiv Mecarbil (OM) is a small molecule allosteric effector of cardiac myosin that is in clinical trials for treatment of systolic heart failure. A detailed kinetic analysis of cardiac myosin has shown that the drug accelerates phosphate release by shifting the equilibrium of the hydrolysis step towards products, leading to a faster transition from weak to strong actin-bound states. The structure of the human β-cardiac motor domain (cMD) with OM bound reveals a single OM-binding site nestled in a narrow cleft separating two domains of the human cMD where it interacts with the key residues that couple lever arm movement to the nucleotide state. In addition, OM induces allosteric changes in three strands of the β-sheet that provides the communication link between the actin-binding interface and the nucleotide pocket. The OM-binding interactions and allosteric changes form the structural basis for the kinetic and mechanical tuning of cardiac myosin. PMID:26246073
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Analytical and numerical analysis of imaging mechanism of dynamic scanning electron microscopy.
Schröter, M-A; Holschneider, M; Sturm, H
2012-11-02
The direct observation of small oscillating structures with the help of a scanning electron beam is a new approach to study the vibrational dynamics of cantilevers and microelectromechanical systems. In the scanning electron microscope, the conventional signal of secondary electrons (SE, dc part) is separated from the signal response of the SE detector, which is correlated to the respective excitation frequency for vibration by means of a lock-in amplifier. The dynamic response is separated either into images of amplitude and phase shift or into real and imaginary parts. Spatial resolution is limited to the diameter of the electron beam. The sensitivity limit to vibrational motion is estimated to be sub-nanometer for high integration times. Due to complex imaging mechanisms, a theoretical model was developed for the interpretation of the obtained measurements, relating cantilever shapes to interaction processes consisting of incident electron beam, electron-lever interaction, emitted electrons and detector response. Conclusions drawn from this new model are compared with numerical results based on the Euler-Bernoulli equation.
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1989-10-20
Phthalocyanines by Thionyl Chloride. Implications for Lithium /Thionyl Chloride Batteries By P.A. Bernstein and A.B.P. Lever* D T IC in NOV.0 3.1W9. M...Thionyl Chloride. Implications forI Lithium /Thionvl Chloride Batteries 12 PERSONAL AUTHOR(S) P.A. Bernstein and A.B.P. Lever* 13a. TYPE OF REPORT 13b...SUBJECT TERMS (Continue on reverse if necessary and identify by olock numoer) FIELD GROUP SUB-GROUP .’ Phthalocyanine," Lithium Battery, Thionyl
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Experimental and Theoretical Investigations of a Mechanical Lever System Driven by a DC Motor
NASA Astrophysics Data System (ADS)
Nana, B.; Fautso Kuiate, G.; Yamgoué, S. B.
This paper presents theoretical and experimental results on the investigation of the dynamics of a nonlinear electromechanical system made of a lever arm actuated by a DC motor and controlled through a repulsive magnetic force. We use the method of harmonic balance to derive oscillatory solutions. Theoretical tools such as, bifurcation diagrams, Lyapunov exponents, phase portraits, are used to unveil the rich nonlinear behavior of the system including chaos and hysteresis. The experimental results are in close accordance with the theoretical predictions.
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Photoelastic analysis of stress distribution in oral rehabilitation.
Turcio, Karina Helga Leal; Goiato, Marcelo Coelho; Gennari Filho, Humberto; dos Santos, Daniela Micheline
2009-03-01
The purpose of this study was to present a literature review about photoelasticity, a laboratory method for evaluation of implants prosthesis behavior. Fixed or removable prostheses function as levers on supporting teeth, allowing forces to cause tooth movement if not carefully planned. Hence, during treatment planning, the dentist must be aware of the biomechanics involved and prevent movement of supporting teeth, decreasing lever-type forces generated by these prosthesis. Photoelastic analysis has great applicability in restorative dentistry as it allows prediction and minimization of biomechanical critical points through modifications in treatment planning.
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Long adaptation reveals mostly attractive shifts of orientation tuning in cat primary visual cortex.
Ghisovan, N; Nemri, A; Shumikhina, S; Molotchnikoff, S
2009-12-15
In the adult brain, sensory cortical neurons undergo transient changes of their response properties following prolonged exposure to an appropriate stimulus (adaptation). In cat V1, orientation-selective cells shift their preferred orientation after being adapted to a non-preferred orientation. There are conflicting reports as to the direction of those shifts, towards (attractive) or away (repulsive) from the adapter. Moreover, the mechanisms underlying attractive shifts remain unexplained. In the present investigation we show that attractive shifts are the most frequent outcome of a 12 min adaptation. Overall, cells displaying selectivity for oblique orientations exhibit significantly larger shifts than cells tuned to cardinal orientations. In addition, cells selective to cardinal orientations had larger shift amplitudes when the absolute difference between the original preferred orientation and the adapting orientation increased. Conversely, cells tuned to oblique orientations exhibited larger shift amplitudes when this absolute orientation difference was narrower. Hence, neurons tuned to oblique contours appear to show more plasticity in response to small perturbations. Two different mechanisms appear to produce attractive and repulsive orientation shifts. Attractive shifts result from concurrent response depression on the non-adapted flank and selective response facilitation on the adapted flank of the orientation tuning curve. In contrast, repulsive shifts are caused solely by response depression on the adapted flank. We suggest that an early mechanism leads to repulsive shifts while attractive shifts engage a subsequent late facilitation. A potential role for attractive shifts may be improved stimulus discrimination around the adapting orientation.
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Metering gun for dispensing precisely measured charges of fluid
NASA Technical Reports Server (NTRS)
Cook, T. A.; Scheibe, H. (Inventor)
1974-01-01
A cyclically operable fluid dispenser for use in dispensing precisely measured charges of potable water aboard spacecraft is described. The dispenser is characterized by (1) a sealed housing adapted to be held within a crewman's palm and coupled with a pressurized source of potable water; (2) a dispensing jet projected from the housing and configured to be received within a crewman's lips; (3) an expansible measuring chamber for measuring charges of drinking water received from the source; (4) and a dispenser actuator including a lever extended from the housing to be digitated for initiating operational cycles, whereby precisely measured charges of potable water selectively are delivered for drinking purposes in a weightless environment.
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Silasi, Gergely; Boyd, Jamie D; Bolanos, Federico; LeDue, Jeff M; Scott, Stephen H; Murphy, Timothy H
2018-01-01
Skilled forelimb function in mice is traditionally studied through behavioral paradigms that require extensive training by investigators and are limited by the number of trials individual animals are able to perform within a supervised session. We developed a skilled lever positioning task that mice can perform within their home cage. The task requires mice to use their forelimb to precisely hold a lever mounted on a rotary encoder within a rewarded position to dispense a water reward. A Raspberry Pi microcomputer is used to record lever position during trials and to control task parameters, thus making this low-footprint apparatus ideal for use within animal housing facilities. Custom Python software automatically increments task difficulty by requiring a longer hold duration, or a more accurate hold position, to dispense a reward. The performance of individual animals within group-housed mice is tracked through radio-frequency identification implants, and data stored on the microcomputer may be accessed remotely through an active internet connection. Mice continuously engage in the task for over 2.5 mo and perform ~500 trials/24 h. Mice required ~15,000 trials to learn to hold the lever within a 10° range for 1.5 s and were able to further refine movement accuracy by limiting their error to a 5° range within each trial. These results demonstrate the feasibility of autonomously training group-housed mice on a forelimb motor task. This paradigm may be used in the future to assess functional recovery after injury or cortical reorganization induced by self-directed motor learning. NEW & NOTEWORTHY We developed a low-cost system for fully autonomous training of group-housed mice on a forelimb motor task. We demonstrate the feasibility of tracking both end-point, as well as kinematic performance of individual mice, with each performing thousands of trials over 2.5 mo. The task is run and controlled by a Raspberry Pi microcomputer, which allows for cages to be monitored remotely through an active internet connection.
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LaCrosse, Amber L.; Burrows, Brian T.; Angulo, Rachel M.; Conrad, Phoebe R.; Himes, Sarah M.; Mathews, Nordia; Wegner, Scott A.; Taylor, Sara B.; Olive, M. Foster
2014-01-01
Rationale Positive allosteric modulators (PAMs) of type 5 metabotropic glutamate receptors (mGluR5) exert pro-cognitive effects in animal models of various neuropsychiatric diseases. However, few studies to date have examined ability of mGluR5 PAMs to reverse cognitive deficits in operant delayed matching/non-matching-to-sample (DMS/DNMS) tasks. Objectives To determine the ability of the mGluR5 PAM 3-cyano-N-1,3-diphenyl-1H-pyrazol-5-yl)benzamide (CDPPB) to reverse set-shifting deficits induced by the NMDA receptor antagonist MK-801. Methods Male Sprague-Dawley rats were initially trained to lever press for sucrose reinforcement under either DMS or DNMS conditions. Following successful acquisition of the task, reinforcement conditions were reversed (DNMS→DMS or DMS→DNMS). In Experiment 1, rats were treated daily prior to each session with either vehicle/vehicle, vehicle/MK-801 (0.06 mg/kg) simultaneously, CDPPB (20 mg/kg)/MK-801 simultaneously, or CDPPB 30 min prior to MK-801. In Experiment 2, rats were treated with either vehicle/vehicle, vehicle/MK-801, or CDPPB 30 min prior to MK-801 only prior to sessions that followed task reversal. Results In Experiment 1, no group differences in initial task acquisition were observed. Rats treated with vehicle+MK−801 showed significant set-shifting impairments following task reversal, which were partially attenuated by simultaneous administration of CDPPB/MK-801, and completely precluded by administration of CDPPB 30 min prior to MK-801. In Experiment 2, MK-801 did not impair reversal learning and no other group differences were observed. Conclusions MK-801 induced deficits in operant set-shifting ability were prevented by pretreatment with CDPPB. MK-801 did not produce deficits in initial task learning or when treatment was initiated following task reversal. PMID:24973895
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A Phaseolus vulgaris Extract Reduces Cue-Induced Reinstatement of Chocolate Seeking in Rats
Lorrai, Irene; Piga, Valentina; Carai, Mauro A. M.; Riva, Antonella; Morazzoni, Paolo; Gessa, Gian Luigi; Colombo, Giancarlo; Maccioni, Paola
2016-01-01
Previous evidence has suggested that treatment with a standardized dry extract of Phaseolus vulgaris reduced intake and operant self-administration of highly palatable foods and fluids in rats and mice. The present study was designed to assess whether such extract was also effective in reducing seeking behavior for a highly hedonic chocolate-flavored beverage, using a “reinstatement” procedure adopted from the drug addiction research field and modeling relapse behavior. Rats were initially trained to lever-respond for the chocolate-flavored beverage under the Fixed Ratio (FR) 10 schedule of reinforcement. Subsequently, rats were exposed to an extinction responding phase, during which lever-responding – being unreinforced – diminished progressively up to extinction. Lever-responding was then powerfully reinstated by the non-contingent presentation of a complex of gustatory, olfactory, auditory, and visual stimuli previously associated to the availability of the chocolate-flavored beverage. Acute, intragastric administration of P. vulgaris dry extract (100 and 500 mg/kg) reduced lever-responding by 40–45%, in comparison to vehicle condition. These results indicate the ability of P. vulgaris dry extract to reduce seeking behavior for a highly palatable nourishment in an experimental model of relapse into disordered eating of palatable foods. The unavailability of the chocolate-flavored beverage in the reinstatement session tends to exclude that the observed effect of the P. vulgaris dry extract was secondary to any inhibition of carbohydrate metabolism; conversely, it is the likely consequence on a central action on the rewarding and hedonic properties of food. PMID:27199752
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Ahrens, Allison M; Ferguson, Lindsay M; Robinson, Terry E; Aldridge, J Wayne
2018-01-01
Some rats are especially prone to attribute incentive salience to a cue (conditioned stimulus, CS) paired with food reward (sign-trackers, STs), but the extent they do so varies as a function of the form of the CS. Other rats respond primarily to the predictive value of a cue (goal-trackers, GTs), regardless of its form. Sign-tracking is associated with greater cue-induced activation of mesolimbic structures than goal-tracking; however, it is unclear how the form of the CS itself influences activity in neural systems involved in incentive salience attribution. Thus, our goal was to determine how different cue modalities affect neural activity in the ventral pallidum (VP), which is known to encode incentive salience attribution, as rats performed a two-CS Pavlovian conditioned approach task in which both a lever-CS and a tone-CS predicted identical food reward. The lever-CS elicited sign-tracking in some rats (STs) and goal-tracking in others (GTs), whereas the tone-CS elicited only goal-tracking in all rats. The lever-CS elicited robust changes in neural activity (sustained tonic increases or decreases in firing) throughout the VP in STs, relative to GTs. These changes were not seen when STs were exposed to the tone-CS, and in GTs there were no differences in firing between the lever-CS and tone-CS. We conclude that neural activity throughout the VP encodes incentive signals and is especially responsive when a cue is of a form that promotes the attribution of incentive salience to it, especially in predisposed individuals.
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Measuring Micro-Friction Torque in MEMS Gas Bearings
Fang, Xudong; Liu, Huan
2016-01-01
An in situ measurement of micro-friction torque in MEMS gas bearings, which has been a challenging research topic for years, is realized by a system designed in this paper. In the system, a high accuracy micro-force sensor and an electronically-driven table are designed, fabricated and utilized. With appropriate installation of the sensor and bearings on the table, the engine rotor can be driven to rotate with the sensor using a silicon lever beam. One end of the beam is fixed to the shaft of the gas bearing, while the other end is free and in contact with the sensor probe tip. When the sensor begins to rotate with the table, the beam is pushed by the sensor probe to rotate in the same direction. For the beam, the friction torque from the gas bearing is balanced by the torque induced by pushing force from the sensor probe. Thus, the friction torque can be calculated as a product of the pushing force measured by the sensor and the lever arm, which is defined as the distance from the sensor probe tip to the centerline of the bearing. Experimental results demonstrate the feasibility of this system, with a sensitivity of 1.285 mV/μN·m in a range of 0 to 11.76 μN·m when the lever arm is 20 mm long. The measuring range can be modified by varying the length of the lever arm. Thus, this system has wide potential applications in measuring the micro-friction torque of gas bearings in rotating MEMS machines. PMID:27213377
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Vollrath-Smith, Fiori R.; Shin, Rick
2011-01-01
Rationale Noncontingent administration of amphetamine into the ventral striatum or systemic nicotine increases responses rewarded by inconsequential visual stimuli. When these drugs are contingently administered, rats learn to self-administer them. We recently found that rats self-administer the GABAB receptor agonist baclofen into the median (MR) or dorsal (DR) raphe nuclei. Objectives We examined whether noncontingent administration of baclofen into the MR or DR increases rats’ investigatory behavior rewarded by a flash of light. Results Contingent presentations of a flash of light slightly increased lever presses. Whereas noncontingent administration of baclofen into the MR or DR did not reliably increase lever presses in the absence of visual stimulus reward, the same manipulation markedly increased lever presses rewarded by the visual stimulus. Heightened locomotor activity induced by intraperitoneal injections of amphetamine (3 mg/kg) failed to concur with increased lever pressing for the visual stimulus. These results indicate that the observed enhancement of visual stimulus seeking is distinct from an enhancement of general locomotor activity. Visual stimulus seeking decreased when baclofen was co-administered with the GABAB receptor antagonist, SCH 50911, confirming the involvement of local GABAB receptors. Seeking for visual stimulus also abated when baclofen administration was preceded by intraperitoneal injections of the dopamine antagonist, SCH 23390 (0.025 mg/kg), suggesting enhanced visual stimulus seeking depends on intact dopamine signals. Conclusions Baclofen administration into the MR or DR increased investigatory behavior induced by visual stimuli. Stimulation of GABAB receptors in the MR and DR appears to disinhibit the motivational process involving stimulus–approach responses. PMID:21904820
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Measurement of the lowest dosage of phenobarbital that can produce drug discrimination in rats
Overton, Donald A.; Stanwood, Gregg D.; Patel, Bhavesh N.; Pragada, Sreenivasa R.; Gordon, M. Kathleen
2009-01-01
Rationale Accurate measurement of the threshold dosage of phenobarbital that can produce drug discrimination (DD) may improve our understanding of the mechanisms and properties of such discrimination. Objectives Compare three methods for determining the threshold dosage for phenobarbital (D) versus no drug (N) DD. Methods Rats learned a D versus N DD in 2-lever operant training chambers. A titration scheme was employed to increase or decrease dosage at the end of each 18-day block of sessions depending on whether the rat had achieved criterion accuracy during the sessions just completed. Three criterion rules were employed, all based on average percent drug lever responses during initial links of the last 6 D and 6 N sessions of a block. The criteria were: D%>66 and N%<33; D%>50 and N%<50; (D%-N%)>33. Two squads of rats were trained, one immediately after the other. Results All rats discriminated drug versus no drug. In most rats, dosage decreased to low levels and then oscillated near the minimum level required to maintain criterion performance. The lowest discriminated dosage significantly differed under the three criterion rules. The squad that was trained 2nd may have benefited by partially duplicating the lever choices of the previous squad. Conclusions The lowest discriminated dosage is influenced by the criterion of discriminative control that is employed, and is higher than the absolute threshold at which discrimination entirely disappears. Threshold estimations closer to absolute threshold can be obtained when criteria are employed that are permissive, and that allow rats to maintain lever preferences. PMID:19082992
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A new criterion for acquisition of nicotine self-administration in rats.
Peartree, Natalie A; Sanabria, Federico; Thiel, Kenneth J; Weber, Suzanne M; Cheung, Timothy H C; Neisewander, Janet L
2012-07-01
Acquisition of nicotine self-administration in rodents is relatively difficult to establish and measures of acquisition rate are sometimes confounded by manipulations used to facilitate the process. This study examined acquisition of nicotine self-administration without such manipulations and used mathematical modeling to define the criterion for acquisition. Rats were given 20 daily 2-h sessions occurring 6 days/week in chambers equipped with active and inactive levers. Each active lever press resulted in nicotine reinforcement (0-0.06 mg/kg, IV) and retraction of both levers for a 20-s time out, whereas inactive lever presses had no consequences. Acquisition was defined for individual rats by the higher likelihood of reinforcers obtained across sessions fitting a logistic over a constant function according to the corrected Akaike Information Criterion (AICc). For rats that acquired self-administration, an AICc-based multi-model comparison demonstrated that the asymptote (highest number of reinforcers/session) and mid-point of the acquisition curve (h; the number of sessions necessary to reach half the asymptote) varied by nicotine dose, with both exhibiting a negative relationship (the higher the dose, the lower number of reinforcers and the lower h). The modeling approach used in this study provides a way of defining acquisition of nicotine self-administration that takes advantage of all data from individual subjects and the procedure used is sensitive to dose differences in the absence of manipulations that influence acquisition (e.g., food restriction, prior food reinforcement, conditioned reinforcers). Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.
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Blanc, Florian; Isabet, Tatiana; Benisty, Hannah; Sweeney, H Lee; Cecchini, Marco; Houdusse, Anne
2018-06-12
Myosins form a class of actin-based, ATPase motor proteins that mediate important cellular functions such as cargo transport and cell motility. Their functional cycle involves two large-scale swings of the lever arm: the force-generating powerstroke, which takes place on actin, and the recovery stroke during which the lever arm is reprimed into an armed configuration. Previous analyses of the prerecovery (postrigor) and postrecovery (prepowerstroke) states predicted that closure of switch II in the ATP binding site precedes the movement of the converter and the lever arm. Here, we report on a crystal structure of myosin VI, called pretransition state (PTS), which was solved at 2.2 Å resolution. Structural analysis and all-atom molecular dynamics simulations are consistent with PTS being an intermediate along the recovery stroke, where the Relay/SH1 elements adopt a postrecovery conformation, and switch II remains open. In this state, the converter appears to be largely uncoupled from the motor domain and explores an ensemble of partially reprimed configurations through extensive, reversible fluctuations. Moreover, we found that the free energy cost of hydrogen-bonding switch II to ATP is lowered by more than 10 kcal/mol compared with the prerecovery state. These results support the conclusion that closing of switch II does not initiate the recovery stroke transition in myosin VI. Rather, they suggest a mechanism in which lever arm repriming would be mostly driven by thermal fluctuations and eventually stabilized by the switch II interaction with the nucleotide in a ratchet-like fashion.
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West, Elizabeth A.
2016-01-01
Nucleus accumbens (NAc) neurons encode features of stimulus learning and action selection associated with rewards. The NAc is necessary for using information about expected outcome values to guide behavior after reinforcer devaluation. Evidence suggests that core and shell subregions may play dissociable roles in guiding motivated behavior. Here, we recorded neural activity in the NAc core and shell during training and performance of a reinforcer devaluation task. Long–Evans male rats were trained that presses on a lever under an illuminated cue light delivered a flavored sucrose reward. On subsequent test days, each rat was given free access to one of two distinctly flavored foods to consume to satiation and were then immediately tested on the lever pressing task under extinction conditions. Rats decreased pressing on the test day when the reinforcer earned during training was the sated flavor (devalued) compared with the test day when the reinforcer was not the sated flavor (nondevalued), demonstrating evidence of outcome-selective devaluation. Cue-selective encoding during training by NAc core (but not shell) neurons reliably predicted subsequent behavioral performance; that is, the greater the percentage of neurons that responded to the cue, the better the rats suppressed responding after devaluation. In contrast, NAc shell (but not core) neurons significantly decreased cue-selective encoding in the devalued condition compared with the nondevalued condition. These data reveal that NAc core and shell neurons encode information differentially about outcome-specific cues after reinforcer devaluation that are related to behavioral performance and outcome value, respectively. SIGNIFICANCE STATEMENT Many neuropsychiatric disorders are marked by impairments in behavioral flexibility. Although the nucleus accumbens (NAc) is required for behavioral flexibility, it is not known how NAc neurons encode this information. Here, we recorded NAc neurons during a training session in which rats learned that a cue predicted a specific reward and during a test session when that reward value was changed. Although encoding in the core during training predicted the ability of rats to change behavior after the reward value was altered, the NAc shell encoded information about the change in reward value during the test session. These findings suggest differential roles of the core and shell in behavioral flexibility. PMID:26818502
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de la Peña, Pilar; Domínguez, Pedro; Barros, Francisco
2018-03-01
Kv11.1 (hERG, KCNH2) is a voltage-gated potassium channel crucial in setting the cardiac rhythm and the electrical behaviour of several non-cardiac cell types. Voltage-dependent gating of Kv11.1 can be reconstructed from non-covalently linked voltage sensing and pore modules (split channels), challenging classical views of voltage-dependent channel activation based on a S4-S5 linker acting as a rigid mechanical lever to open the gate. Progressive displacement of the split position from the end to the beginning of the S4-S5 linker induces an increasing negative shift in activation voltage dependence, a reduced z g value and a more negative ΔG 0 for current activation, an almost complete abolition of the activation time course sigmoid shape and a slowing of the voltage-dependent deactivation. Channels disconnected at the S4-S5 linker near the S4 helix show a destabilization of the closed state(s). Furthermore, the isochronal ion current mode shift magnitude is clearly reduced in the different splits. Interestingly, the progressive modifications of voltage dependence activation gating by changing the split position are accompanied by a shift in the voltage-dependent availability to a methanethiosulfonate reagent of a Cys introduced at the upper S4 helix. Our data demonstrate for the first time that alterations in the covalent connection between the voltage sensor and the pore domains impact on the structural reorganizations of the voltage sensor domain. Also, they support the hypothesis that the S4-S5 linker integrates signals coming from other cytoplasmic domains that constitute either an important component or a crucial regulator of the gating machinery in Kv11.1 and other KCNH channels.
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Kriegel, J; Rebhandl, E; Reckwitz, N; Hockl, W
2016-12-01
Current and projected general practitioner (GP) and primary care in Austria shows structural and process inadequacies in the quality as well as assurance of healthcare supply. The aim is therefore to develop solution- and patient-oriented measures that take patient-related requirements and medical perspectives into account. Using an effect matrix, subjective expert and user priorities were ascertained, cause and effect relationships were examined, and an expanded circle of success for the optimization of GP and primary care in Upper Austria was developed. Through this, the relevant levers for target-oriented development and optimization of the complex system of GP and primary care in Upper Austria were identified; these are training to become general practitioners, entrepreneurs as well as management and coordination. It is necessary to further adapt the identified levers conceptually and operationally in a targeted approach. This is to be achieved by means of the primary health care (PHC) concept as well as management tools and information and communication technologies (ICT) associated with it. © Georg Thieme Verlag KG Stuttgart · New York.
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The role of pedunculopontine nucleus in choice behavior under risk
Leblond, Mona; Sukharnikova, Tatyana; Yu, Chunxiu; Rossi, Mark A.; Yin, Henry H.
2014-01-01
The dopaminergic projections to the basal ganglia have long been implicated in reward guided behavior and decision making, yet little is known about the role of the posterior pedunculopontine nucleus (pPPN), a major source of excitatory input to the mesolimbic dopamine system. Here we studied the contributions of pPPN to decision making under risk, using excitoxic lesions and reversible inactivation in rats. Rats could choose between two options: a small but certain reward on one lever, or a large but uncertain reward on the other lever. The overall payoff associated with each choice is the same, but the reward variance (risk) associated with the risky choice is much higher. In Experiment 1, we showed that excitotoxic lesions of the pPPN before training did not affect acquisition of lever pressing. But whereas the controls strongly preferred the safe choice, the lesioned rats did not. In Experiment 2, we found that muscimol inactivation of the pPPN also reversibly altered choice behavior. These results show that permanent lesions or reversible inactivation of the pPPN both abolish risk aversion in decision making. PMID:24617747
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2015-01-01
Abstract Stored memories are dynamic and, when reactivated, can undergo a process of destabilization and reconsolidation to update them with new information. Reconsolidation has been shown for a variety of experimental settings; most recently for well-learned instrumental memories, a class of memory previously thought not to undergo reconsolidation. Here we tested, in rats, whether a weakly-trained lever-pressing memory destabilized following a shift in reinforcement contingency. We show that lever-pressing memory for both sucrose and cocaine reinforcement destabilized under appropriate conditions, and that the reconsolidation of this memory was impaired by systemic administration of the NMDA receptor (NMDAR) antagonist [5R,10S]-[+]-5-methyl-10,1-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (MK-801). We went on to investigate the potential role of the nucleus accumbens (NAc) in the reconsolidation of sucrose-reinforced instrumental memories, showing that co-infusion of the NMDAR antagonist 2-amino-5-phosphonopentanoic acid (AP-5) and the dopamine-1 receptor (D1R) antagonist 7-chloro-3-methyl-1-phenyl-1,2,4,5-tetrahydro-3-benzazepin-8-ol (SCH23390) into the NAc prior to memory reactivation impaired reconsolidation; however, there was no effect when these drugs were infused alone. Further investigation of this effect suggests the combined infusion disrupted the reconsolidation of pavlovian components of memory, and we hypothesize that coactivation of accumbal D1Rs and NMDARs may contribute to both the destabilization and reconsolidation of appetitive memory. Our work demonstrates that weakly-trained instrumental memories undergo reconsolidation under similar parameters to well-trained ones, and also suggests that receptor coactivation in the NAc may contribute to memory destabilization. Furthermore, it provides an important demonstration of the therapeutic potential of reconsolidation-based treatments that target the instrumental components of memory in maladaptive drug seeking. PMID:26464973
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Drivers of Environmental Institutional Dynamics in Decentralized African Countries.
Hassenforder, Emeline; Barreteau, Olivier; Daniell, Katherine Anne; Pittock, Jamie; Ferrand, Nils
2015-12-01
This paper builds on the assumption that an effective approach to support the sustainability of natural resource management initiatives is institutional "bricolage." We argue that participatory planning processes can foster institutional bricolage by encouraging stakeholders to make their own arrangements based on the hybridization of old and new institutions. This papers aims at identifying how participatory process facilitators can encourage institutional bricolage. Specifically the paper investigates the specific contextual and procedural drivers of institutional dynamics in two case studies: the Rwenzori region in Uganda and the Fogera woreda in Ethiopia. In both cases, participatory planning processes were implemented. This research has three innovative aspects. First, it establishes a clear distinction between six terms which are useful for identifying, describing, and analyzing institutional dynamics: formal and informal; institutions and organizations; and emergence and change. Secondly, it compares the contrasting institutional dynamics in the two case studies. Thirdly, process-tracing is used to identify contextual and procedural drivers to institutional dynamics. We assume that procedural drivers can be used as "levers" by facilitators to trigger institutional bricolage. We found that facilitators need to pay particular attention to the institutional context in which the participatory planning process takes place, and especially at existing institutional gaps or failures. We identified three clusters of procedural levers: the selection and engagement of participants; the legitimacy, knowledge, and ideas of facilitators; and the design of the process, including the scale at which it is developed, the participatory tools used and the management of the diversity of frames.
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Drivers of Environmental Institutional Dynamics in Decentralized African Countries
NASA Astrophysics Data System (ADS)
Hassenforder, Emeline; Barreteau, Olivier; Daniell, Katherine Anne; Pittock, Jamie; Ferrand, Nils
2015-12-01
This paper builds on the assumption that an effective approach to support the sustainability of natural resource management initiatives is institutional "bricolage." We argue that participatory planning processes can foster institutional bricolage by encouraging stakeholders to make their own arrangements based on the hybridization of old and new institutions. This papers aims at identifying how participatory process facilitators can encourage institutional bricolage. Specifically the paper investigates the specific contextual and procedural drivers of institutional dynamics in two case studies: the Rwenzori region in Uganda and the Fogera woreda in Ethiopia. In both cases, participatory planning processes were implemented. This research has three innovative aspects. First, it establishes a clear distinction between six terms which are useful for identifying, describing, and analyzing institutional dynamics: formal and informal; institutions and organizations; and emergence and change. Secondly, it compares the contrasting institutional dynamics in the two case studies. Thirdly, process-tracing is used to identify contextual and procedural drivers to institutional dynamics. We assume that procedural drivers can be used as "levers" by facilitators to trigger institutional bricolage. We found that facilitators need to pay particular attention to the institutional context in which the participatory planning process takes place, and especially at existing institutional gaps or failures. We identified three clusters of procedural levers: the selection and engagement of participants; the legitimacy, knowledge, and ideas of facilitators; and the design of the process, including the scale at which it is developed, the participatory tools used and the management of the diversity of frames.
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Morphologic Variability of the Shoulder between the Populations of North American and East Asian.
Cabezas, Andres F; Krebes, Kristi; Hussey, Michael M; Santoni, Brandon G; Kim, Hyuong Sik; Frankle, Mark A; Oh, Joo Han
2016-09-01
The aim of this study was to determine if there were significant differences in glenohumeral joint morphology between North American and East Asian populations that may influence sizing and selection of shoulder arthroplasty systems. Computed tomography reconstructions of 92 North American and 58 East Asian patients were used to perform 3-dimensional measurements. The proximal humeral position was normalized in all patients by aligning it with the scapular plane utilizing anatomic landmarks. Measurements were performed on the humerus and scapula and included coronal and axial humeral head radius, humeral neck shaft and articular arc angles, glenoid height and width, and critical shoulder angle. Glenohumeral relationships were also measured and included lateral distance to the greater tuberosity and acromion, abduction lever arm, and acromial index. Parametric and nonparametric statistical analyses were used to compare population metrics. East Asian glenohumeral measurements were significantly smaller for all linear metrics (p < 0.05), with the exception of acromial length, which was greater than in the North American cohort (p < 0.001). The increase in acromial length affected all measurements involving the acromion including abduction lever arms. No difference was found between the neck shaft and articular angular measurements. The East Asian population exhibited smaller shoulder morphometrics than their North American cohort, with the exception of an extended acromial overhang. The morphologic data can provide some additional factors to consider when choosing an optimal shoulder implant for the East Asian population, in addition to creating future designs that may better accommodate this population.
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Monsey, Melissa S; Sanchez, Hayde; Taylor, Jane R
2017-02-01
Sustained abstinence from cocaine use is frequently compromised by exposure to environmental stimuli that have previously been strongly associated with drug taking. Such cues trigger memories of the effects of the drug, leading to craving and potential relapse. Our work has demonstrated that manipulating cocaine-cue memories by destabilizing them through interfering with the reconsolidation process is one potential therapeutic tool by which to prolong abstinence. Here, we examine the use of the naturally occurring amnestic agent garcinol to manipulate an established cocaine-cue memory. Rats underwent 12 days of cocaine self-administration training during which time active lever presses resulted in an i.v. infusion of cocaine that was paired with a light/tone cue. Next rats underwent lever extinction for 8 days followed by light/tone reactivation and a test of cue-induced cocaine-seeking behavior. Systemic injection of garcinol 30 min after reactivation significantly impaired the reconsolidation of the cocaine-associated cue memory. Further testing revealed that garcinol had no effect on drug-induced cocaine-seeking, but was capable of blocking the initial conditioned reinforcing properties of the cue and prevents the acquisition of a new response. Additional experiments showed that the effects of garcinol are specific to reactivated memories only, temporally constrained, cue-specific, long-lasting, and persist following extended cocaine access. These data provide strong evidence that the naturally occurring compound, garcinol, may be a potentially useful tool to sustain abstinence from drug abuse.
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Monsey, Melissa S; Sanchez, Hayde; Taylor, Jane R
2017-01-01
Sustained abstinence from cocaine use is frequently compromised by exposure to environmental stimuli that have previously been strongly associated with drug taking. Such cues trigger memories of the effects of the drug, leading to craving and potential relapse. Our work has demonstrated that manipulating cocaine-cue memories by destabilizing them through interfering with the reconsolidation process is one potential therapeutic tool by which to prolong abstinence. Here, we examine the use of the naturally occurring amnestic agent garcinol to manipulate an established cocaine-cue memory. Rats underwent 12 days of cocaine self-administration training during which time active lever presses resulted in an i.v. infusion of cocaine that was paired with a light/tone cue. Next rats underwent lever extinction for 8 days followed by light/tone reactivation and a test of cue-induced cocaine-seeking behavior. Systemic injection of garcinol 30 min after reactivation significantly impaired the reconsolidation of the cocaine-associated cue memory. Further testing revealed that garcinol had no effect on drug-induced cocaine-seeking, but was capable of blocking the initial conditioned reinforcing properties of the cue and prevents the acquisition of a new response. Additional experiments showed that the effects of garcinol are specific to reactivated memories only, temporally constrained, cue-specific, long-lasting, and persist following extended cocaine access. These data provide strong evidence that the naturally occurring compound, garcinol, may be a potentially useful tool to sustain abstinence from drug abuse. PMID:27380937
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Sanchez-Alavez, Manuel; Ehlers, Cindy L.
2015-01-01
The cholinergic system in the brain is involved in attentional processes that are engaged for the identification and selection of relevant information in the environment and the formation of new stimulus associations. In the present study we determined the effects of cholinergic lesions of nucleus basalis magnocellularis (NBM) on amplitude and phase characteristics of event related oscillations (EROs) generated in an auditory active discrimination task in rats. Rats were trained to press a lever to begin a series of 1K Hz tones and to release the lever upon hearing a 2 kHz tone. A time-frequency based representation was used to determine ERO energy and phase synchronization (phase lock index, PLI) across trials, recorded within frontal cortical structures. Lesions in NBM produced by an infusion of a-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) resulted in (1) a reduction of the number of correct behavioral responses in the active discrimination task, (2) an increase in ERO energy in the delta frequency bands (3) an increase in theta, alpha and beta ERO energy in the N1, P3a and P3b regions of interest (ROI), and (4) an increase in PLI in the theta frequency band in the N1 ROIs. These studies suggest that the NBM cholinergic system is involved in maintaining the synchronization/phase resetting of oscillations in different frequencies in response to the presentation of the target stimuli in an active discrimination task. PMID:25660307
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Orthopedic surgery in cerebral palsy: Instructional course lecture
Sharan, Deepak
2017-01-01
Orthopedic surgery (OS) plays an important role in the management of cerebral palsy (CP). The objectives of OS are to optimize functions and prevent deformity. Newer developments in OS for CP include emphasis on hip surveillance, minimally invasive procedures, use of external fixators instead of plates and screws, better understanding of lever arm dysfunctions (that can only be corrected by bony OS), orthopedic selective spasticity-control surgery, and single-event multilevel lever arm restoration and anti spasticity surgery, which have led to significant improvements in gross motor function and ambulation, especially in spastic quadriplegia, athetosis, and dystonia. The results of OS can be dramatic and life altering for the person with CP and their caregivers if it is performed meticulously by a specialized surgical team, at the appropriate age, for the correct indications, employing sound biomechanical principles and is followed by physician-led, protocol based, intensive, multidisciplinary, institutional rehabilitation, and long term followup. However, OS can be a double-edged sword, and if performed less than optimally, and without the supporting multidisciplinary medical and rehabilitation team, expertise and infrastructure, it often leads to significant functional worsening of the person with CP, including irretrievable loss of previous ambulatory capacity. OS must be integrated into the long term management of the person with CP and should be anticipated and planned at the optimal time and not viewed as a “last resort” intervention or failure of rehabilitation. This instructional course lecture reviews the relevant contemporary principles and techniques of OS in CP. PMID:28566775
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System analysis of force feedback microscopy
NASA Astrophysics Data System (ADS)
Rodrigues, Mario S.; Costa, Luca; Chevrier, Joël; Comin, Fabio
2014-02-01
It was shown recently that the Force Feedback Microscope (FFM) can avoid the jump-to-contact in Atomic force Microscopy even when the cantilevers used are very soft, thus increasing force resolution. In this letter, we explore theoretical aspects of the associated real time control of the tip position. We take into account lever parameters such as the lever characteristics in its environment, spring constant, mass, dissipation coefficient, and the operating conditions such as controller gains and interaction force. We show how the controller parameters are determined so that the FFM functions at its best and estimate the bandwidth of the system under these conditions.
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Studying damage accumulation in martensitic corrosion-resistant steel under cold radial reduction
NASA Astrophysics Data System (ADS)
Karamyshev, A. P.; Nekrasov, I. I.; Nesterenko, A. V.; Parshin, V. S.; Smirnov, S. V.; Shveikin, V. P.; Fedulov, A. A.
2017-12-01
Cold radial reduction of specimens made of the Kh17N2 corrosion-resistant martensitic steel is studied on a lever-type radial-forging machine (RFM). The mechanical properties of the deformed specimens, the "damage accumulation - strain" relation in the specimens are obtained with the application of hydrostatic and fractographic methods for fractured specimens. The damage of the Kh17N2 corrosion-resistant steel is evaluated as a result of an experimental study considering the data of simulation by a complex finite element model of cold deformation on a lever-type RFM.
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Tahara, Tatsuki; Mori, Ryota; Kikunaga, Shuhei; Arai, Yasuhiko; Takaki, Yasuhiro
2015-06-15
Dual-wavelength phase-shifting digital holography that selectively extracts wavelength information from five wavelength-multiplexed holograms is presented. Specific phase shifts for respective wavelengths are introduced to remove the crosstalk components and extract only the object wave at the desired wavelength from the holograms. Object waves in multiple wavelengths are selectively extracted by utilizing 2π ambiguity and the subtraction procedures based on phase-shifting interferometry. Numerical results show the validity of the proposed technique. The proposed technique is also experimentally demonstrated.
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Maggio, Sarah E; Saunders, Meredith A; Baxter, Thomas A; Nixon, Kimberly; Prendergast, Mark A; Zheng, Guangrong; Crooks, Peter; Dwoskin, Linda P; Slack, Rachel D; Newman, Amy H; Bell, Richard L; Bardo, Michael T
2018-05-01
Co-users of alcohol and nicotine are the largest group of polysubstance users worldwide. Commonalities in mechanisms of action for ethanol (EtOH) and nicotine proposes the possibility of developing a single pharmacotherapeutic to treat co-use. Toward developing a preclinical model of co-use, female alcohol-preferring (P) rats were trained for voluntary EtOH drinking and i.v. nicotine self-administration in three phases: (1) EtOH alone (0 vs. 15%, two-bottle choice), (2) nicotine alone (0.03 mg/kg/infusion, active vs. inactive lever), and (3) concurrent access to both EtOH and nicotine. Using this model, we examined the effects of (1) varenicline, a nicotinic acetylcholine receptor (nAChR) partial agonist with high affinity for the α4β2* subtype; (2) r-bPiDI, a subtype-selective antagonist at α6β2* nAChRs; and (3) (R)-modafinil, an atypical inhibitor of the dopamine transporter (DAT). In phases 1 and 2, pharmacologically relevant intake of EtOH and nicotine was achieved. In the concurrent access phase (phase 3), EtOH consumption decreased while nicotine intake increased relative to phases 1 and 2. For drug pretreatments, in the EtOH access phase (phase 1), (R)-modafinil (100 mg/kg) decreased EtOH consumption, with no effect on water consumption. In the concurrent access phase, varenicline (3 mg/kg), r-bPiDI (20 mg/kg), and (R)-modafinil (100 mg/kg) decreased nicotine self-administration but did not alter EtOH consumption, water consumption, or inactive lever pressing. These results indicate that therapeutics which may be useful for smoking cessation via selective inhibition of α4β2* or α6β2* nAChRs, or DAT inhibition, may not be sufficient to treat EtOH and nicotine co-use.
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Selective data segment monitoring system. [using shift registers
NASA Technical Reports Server (NTRS)
Wirth, M. N. (Inventor)
1976-01-01
High speed data monitoring apparatus is described for displaying the bit pattern of a selected portion of a block of transmitted data comprising a shift register for receiving the transmitted data and for temporarily containing the consecutive data bits. A programmable sync detector for monitoring the contents of the shift register and for generating a sync signal when the shift register contains a predetermined sync code is included. A counter is described for counting the data bits input to the shift register after the sync signal is generated and for generating a count complete signal when a selected number of data bits have been input to the register. A data storage device is used for storing the contents of the shift register at the time the count complete signal is generated.
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Barrett, Andrew C; Negus, S Stevens; Mello, Nancy K; Caine, S Barak
2005-11-01
Recent studies indicate that GABAergic ligands modulate abuse-related effects of cocaine. The goal of this study was to evaluate the effects of a mechanistically diverse group of GABAergic ligands on the discriminative stimulus and reinforcing effects of cocaine in rats. One group of rats was trained to discriminate 5.6 mg/kg cocaine from saline in a two-lever, food-reinforced, drug discrimination procedure. In two other groups, responding was maintained by cocaine (0-3.2 mg/kg/injection) or liquid food (0-100%) under a fixed ratio 5 schedule. Six GABA agonists were tested: the GABA-A receptor agonist muscimol, the GABA-B receptor agonist baclofen, the GABA transaminase inhibitor gamma-vinyl-GABA (GVG), and three GABA-A receptor modulators (the barbiturate pentobarbital, the high-efficacy benzodiazepine midazolam, and the low-efficacy benzodiazepine enazenil). When tested alone, none of the compounds substituted fully for the discriminative stimulus effects of cocaine. As acute pretreatments, select doses of midazolam and pentobarbital produced 2.2- to 3.6-fold rightward shifts in the cocaine dose-effect function. In contrast, muscimol, baclofen, GVG, and enazenil failed to alter the discriminative stimulus effects of cocaine. In assays of cocaine- and food-maintained responding, midazolam and pentobarbital decreased cocaine self-administration at doses 9.6- and 3.3-fold lower, respectively, than those that decreased food-maintained responding. In contrast, muscimol, baclofen, and GVG decreased cocaine self-administration at doses that also decreased food-maintained responding. Enazenil failed to alter cocaine self-administration. Together with previous studies, these data suggest that among mechanistically diverse GABA agonists, high-efficacy GABA-A modulators may be the most effective for modifying the abuse-related effects of cocaine.
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Nunes, Eric J.; Randall, Patrick A.; Hart, Evan E.; Freeland, Charlotte; Yohn, Samantha E.; Baqi, Younis; Müller, Christa E.; López-Cruz, Laura; Correa, Mercè
2013-01-01
Motivated behaviors are often characterized by a high degree of behavioral activation, and work output and organisms frequently make effort-related decisions based upon cost/benefit analyses. Moreover, people with major depression and other disorders often show effort-related motivational symptoms such as anergia, psychomotor retardation, and fatigue. It has been suggested that tasks measuring effort-related choice behavior could be used as animal models of the motivational symptoms of depression, and the present studies characterized the effort-related effects of the vesicular monoamine transport (VMAT) inhibitor tetrabenazine. Tetrabenazine produces depressive symptoms in humans and, because of its selective inhibition of VMAT-2, it preferentially depletes dopamine (DA). Rats were assessed using a concurrent fixed-ratio 5/chow feeding choice task that is known to be sensitive to dopaminergic manipulations. Tetrabenazine shifted response choice in rats, producing a dose-related decrease in lever pressing and a concomitant increase in chow intake. However, it did not alter food intake or preference in parallel free-feeding choice studies. The effects of tetrabenazine on effort-related choice were reversed by the adenosine A2A antagonist MSX-3 and the antidepressant bupropion. A behaviorally active dose of tetrabenazine decreased extracellular DA in nucleus accumbens and increased expression of DARPP-32 in accumbens medium spiny neurons in a pattern indicative of reduced transmission at both D1 and D2 DA receptors. These experiments demonstrate that tetrabenazine, which is used in animal models to produce depression-like effects, can alter effort-related choice behavior. These studies have implications for the development of animal models of the motivational symptoms of depression and related disorders. PMID:24305809
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Nunes, Eric J; Randall, Patrick A; Podurgiel, Samantha; Correa, Mercè; Salamone, John D
2013-11-01
Mesolimbic dopamine (DA) is a critical component of the brain circuitry regulating behavioral activation and effort-related processes. Although nucleus accumbens (NAc) DA depletions or antagonism leave aspects of appetite and primary food motivation intact, rats with impaired DA transmission reallocate their instrumental behavior away from food-reinforced tasks with high response requirements, and instead select less effortful food-seeking behaviors. Previous work showed that adenosine A2A antagonists can reverse the effects of DA D2 antagonists on effort-related choice, and that stimulation of adenosine A2A receptors produces behavioral effects that are similar to those induced by DA antagonism. The present review summarizes the literature on the role of NAc DA and adenosine in effort-related processes, and also presents original data on the effects of local stimulation of muscarinic acetylcholine receptors in NAc core. Local injections of the muscarinic agonist pilocarpine directly into NAc core produces shifts in effort-related choice behavior similar to those induced by DA antagonism or A2A receptor stimulation, decreasing lever pressing but increasing chow intake in rats responding on a concurrent fixed ratio/chow feeding choice task. In contrast, injections into a neostriatal control site dorsal to the NAc were ineffective. The actions of pilocarpine on this task were attenuated by co-administration of the muscarinic antagonist scopolamine. Thus, drugs that act on DA, adenosine A2A, and muscarinic receptors regulate effort-related choice behavior, which may have implications for the treatment of psychiatric symptoms such as psychomotor slowing, fatigue or anergia that can be observed in depression and other disorders. Copyright © 2013 Elsevier Ltd. All rights reserved.
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Kress, Nico; Rapp, Johanna; Hauer, Bernhard
2017-04-18
A deeper understanding of the >99 % S-selective reduction of both isomers of citral catalyzed by NCR ene reductase was achieved by active-site mutational studies and docking simulation. Though structurally similar, the E/Z isomers of citral showed a significantly varying selectivity response to introduced mutations. Although it was possible to invert (E)-citral reduction enantioselectivity to ee 46 % (R) by introducing mutation W66A, for (Z)-citral it remained ≥88 % (S) for all single-residue variants. Residue 66 seems to act as a lever for opposite binding modes. This was underlined by a W66A-based double-mutant library that enhanced the (E)-citral derived enantioselectivity to 63 % (R) and significantly lowered the S selectivity for (Z)-citral to 44 % (S). Formation of (R)-citronellal from an (E/Z)-citral mixture is a desire in industrial (-)-menthol synthesis. Our findings pave the way for a rational enzyme engineering solution. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
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Modelling Per Capita Water Demand Change to Support System Planning
NASA Astrophysics Data System (ADS)
Garcia, M. E.; Islam, S.
2016-12-01
Water utilities have a number of levers to influence customer water usage. These include levers to proactively slow demand growth over time such as building and landscape codes as well as levers to decrease demands quickly in response to water stress including price increases, education campaigns, water restrictions, and incentive programs. Even actions aimed at short term reductions can result in long term water usage declines when substantial changes are made in water efficiency, as in incentives for fixture replacement or turf removal, or usage patterns such as permanent lawn watering restrictions. Demand change is therefore linked to hydrological conditions and to the effects of past management decisions - both typically included in water supply planning models. Yet, demand is typically incorporated exogenously using scenarios or endogenously using only price, though utilities also use rules and incentives issued in response to water stress and codes specifying standards for new construction to influence water usage. Explicitly including these policy levers in planning models enables concurrent testing of infrastructure and policy strategies and illuminates interactions between the two. The City of Las Vegas is used as a case study to develop and demonstrate this modeling approach. First, a statistical analysis of system data was employed to rule out alternate hypotheses of per capita demand decrease such as changes in population density and economic structure. Next, four demand sub-models were developed including one baseline model in which demand is a function of only price. The sub-models were then calibrated and tested using monthly data from 1997 to 2012. Finally, the best performing sub-model was integrated with a full supply and demand model. The results highlight the importance of both modeling water demand dynamics endogenously and taking a broader view of the variables influencing demand change.
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Bushnell, M C; Weiss, S J
1977-03-01
In Experiments I and II, rats were trained to respond on one lever during light and another during tone. The absence of tone and light controlled response cessation. In the multiple schedule of Experiment I, all reinforcements were received for responding in tone or light; in the chain schedule of Experiment II, all reinforcements were received in no tone + no light for not responding. Experiment I subjects, for which tone and light were associated with response and reinforcement increase, responded significantly more to tone-plus-light than to tone or light alone (additive summation). Experiment II subjects, for which tone and light were associated with response increase and reinforcement decrease, responded comparably to tone, light, and tone + light. Thus, additive summation was observed when stimulus-response and stimulus-reinforcer associations in tone and light were both positive, but not when they were conflicting. All subjects in both experiments responded predominantly on the light-correlated lever during tone + light, even when light intensity was reduced in testing. Furthermore, when a light was presented to a subject engaged in tone-associated responding, all subjects immediately switched the locus of responding to the light-correlated lever. No change in locus occurred when a tone was presented to a subject engaged in light-associated responding, irrespective of the stimulus-reinforcer association conditioned to tone. The light-lever preference in tone + light indicates that the heightened responding observed in Experiment I was not the summation of tone-associated behavior with light-associated behavior. Rather, it appears to be the result of a facilitation of one operant (light-associated responding) by the reinforcement-associated cue for the other.
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Sable, Helen J. K.; Monaikul, Supida; Poon, Emily; Eubig, Paul A.; Schantz, Susan L.
2010-01-01
Polychlorinated biphenyls (PCBs) are environmental neurotoxicants known to affect the brain dopaminergic (DA) system. This project investigated whether developmental exposure to PCBs would alter the discriminative stimulus effects of psychostimulant drugs known to act on the DA system. Female Long-Evans rats were orally exposed to 0, 3, or 6 mg/kg/day of an environmentally relevant PCB mixture from four weeks prior to breeding through weaning of their litters on PND 21. When they reached adulthood one male and female/litter were trained to discriminate cocaine (10.0 mg/kg, IP) from saline by repeatedly pairing cocaine injections with reinforcement on one operant response lever, and saline injections with reinforcement on the other lever. After response training, generalization tests to four lower doses of cocaine (7.5, 5.0, 2.5, and 1.25 mg/kg, IP) and to amphetamine (1.0, 0.5, 0.25, and 0.125 mg/kg, IP) were given two days/week, with additional training dose days in-between. Percent responding of the PCB-exposed rats on the cocaine-paired lever was significantly higher than that of controls for the highest generalization dose of cocaine, and lower than that of controls for the highest dose of amphetamine. Response rate and percent responding on the cocaine lever did not differ among the exposure groups on the days when the training dose of cocaine was given, suggesting the generalization test results were not due to pre-existing differences in discrimination ability or rate of responding. These findings suggest developmental PCB exposure can alter the interoceptive cues of psychostimulants. PMID:20933596
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Learning not to respond: Role of the hippocampus in withholding responses during omission training.
White, Norman M; Naeem, Maliha
2017-02-01
Autoshaping is a Pavlovian learning paradigm in which rats experience pairings of a CS and a US independently of their behavior. When the CS is a lever inserted into the test cage and the US is food delivered to an adjacent magazine, many rats acquire a lever-pressing response called 'sign-tracking' even though that response has no effect on the occurrence of either the CS or the US. Since these lever presses are always followed by the US, it has been suggested that sign-tracking could be due to unintended reinforcement of the response. To eliminate the possibility of such instrumental learning the omission schedule, in which a response to the CS cancels the US, was introduced. Previous research has shown that training rats on autoshaping and switching them to an omission schedule generally reduces but does not eliminate sign-tracking, suggesting that it may be due to both Pavlovian and instrumental learning. In the present study naive rats trained on an omission schedule sign-tracked less than a control group exposed to random, unpaired CS and US presentations, suggesting that they learned to withhold the lever press response because of the negative contingency between that response and the US. In a second experiment rats with dorsal hippocampus lesions sign-tracked more than sham-lesioned rats on omission schedules, suggesting that this case of learning not to respond is hippocampus-based. This conclusion is consistent with many previous findings on the inability of hippocampal rats to withhold or suppress responding, and with studies suggesting that one form of extinction of learned responses in normal rats is due to competition from hippocampus-based learning not to respond. Copyright © 2016 Elsevier B.V. All rights reserved.
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Mechanized fluid connector and assembly tool system with ball detents
NASA Technical Reports Server (NTRS)
Zentner, Ronald C. (Inventor); Smith, Steven A. (Inventor)
1991-01-01
A fluid connector system is disclosed which includes a modified plumbing union having a rotatable member for drawing said union into a fluid tight condition. A drive tool is electric motor actuated and includes a reduction gear train providing an output gear engaging an integral peripheral spur gear on the rotatable member. Coaxial alignment means are attached to both the connector assembly and the drive tool. A hand lever actuated latching system includes a plurality of circumferentially spaced latching balls selectively wedged against the alignment means attached to the connector assembly or to secure the drive tool with its output gear in mesh with the integral peripheral spur gear. The drive motor is torque, speed, and direction controllable.
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Braking System for Wind Turbines
NASA Technical Reports Server (NTRS)
Krysiak, J. E.; Webb, F. E.
1987-01-01
Operating turbine stopped smoothly by fail-safe mechanism. Windturbine braking systems improved by system consisting of two large steel-alloy disks mounted on high-speed shaft of gear box, and brakepad assembly mounted on bracket fastened to top of gear box. Lever arms (with brake pads) actuated by spring-powered, pneumatic cylinders connected to these arms. Springs give specific spring-loading constant and exert predetermined load onto brake pads through lever arms. Pneumatic cylinders actuated positively to compress springs and disengage brake pads from disks. During power failure, brakes automatically lock onto disks, producing highly reliable, fail-safe stops. System doubles as stopping brake and "parking" brake.
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Major, Matthew J; Howard, David; Jones, Rebecca; Twiste, Martin
2012-06-01
Unlike sagittal plane prosthesis alignment, few studies have observed the effects of transverse plane alignment on gait and prosthesis behaviour. Changes in transverse plane rotation angle will rotate the points of loading on the prosthesis during stance and may alter its mechanical behaviour. This study observed the effects of increasing the external transverse plane rotation angle, or toe-out, on foot compression and effective lever arm of three commonly prescribed prosthetic feet. The roll-over shape of a SACH, Flex and single-axis foot was measured at four external rotation angle conditions (0°, 5°, 7° and 12° relative to neutral). Differences in foot compression between conditions were measured as average distance between roll-over shapes. Increasing the transverse plane rotation angle did not affect foot compression. However, it did affect the effective lever arm, which was maximized with the 5° condition, although differences between conditions were small. Increasing the transverse plane rotation angle of prosthetic feet by up to 12° beyond neutral has minimal effects on their mechanical behaviour in the plane of walking progression during weight-bearing.
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Prause, N; Heiman, J R
2009-05-01
The labial thermistor offers several potential psychometric advantages over existing measures of female sexual response; however, the thermistor lacked data to support these presumed advantages, especially with respect to its discriminant validity. In this study, both the labial thermistor was worn simultaneously with the vaginal photoplethysmograph as women viewed films. They also indicated their level of subjective sexual arousal using a lever. The labial thermistor discriminated sexual from nonsexual arousing stimuli and was sensitive to different levels of sexual arousal. The correspondence of the instrument with subjective sexual arousal, measured using a continuous lever, was lower during the mildly arousing sexual film and higher during the maximally sexual arousing film. One woman reported that the labial thermistor was very uncomfortable, while others indicated no or mild discomfort from each instrument. The vaginal photoplethysmograph largely replicated the effects documented by the labial thermistor, although it did not discriminate sexual stimuli of different intensity nor correspond with women's continuous lever responses as closely during the more arousing stimulus. Difficulties recording simultaneously with these instruments are noted. The labial thermistor adequately discriminates between generally arousing and sexually arousing stimuli, increasing its utility as a measure for between-subject study designs.
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NASA Astrophysics Data System (ADS)
Fitzpatrick, John J.
2017-11-01
This paper questions if engineering educators are producing engineers that are accelerating humanity along an unsustainable path. Even though technology and engineering are important drivers in trying to move humanity towards an environmentally sustainable paradigm, the paper suggests that maybe the most important levers and challenges lie in the economic and social domains. Short case studies of energy efficiency, the experience of the industrialist Ray Anderson and the authors own reflection of teaching chemical engineering students are used to highlight this. Engineering/technological innovation may not be enough and is often counteracted by the rebound effect and the current dominant neoclassical economic paradigm. The paper discusses what engineering educators can do to produce sustainability informed engineers who are better able to engage with the economic and social dimensions of sustainability. Some suggestions for engaging engineering students with the economic and social dimensions of environmental sustainability are provided. Engineers must somehow find ways, not just to influence technological levers (which are very important) but also to influence economic and social levers so that changes in economic and social behaviours can complement and facilitate technological change in moving humanity to an environmentally sustainable paradigm.
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Utilization of a Terrestrial Laser Scanner for the Calibration of Mobile Mapping Systems
Hong, Seunghwan; Park, Ilsuk; Lee, Jisang; Lim, Kwangyong; Choi, Yoonjo; Sohn, Hong-Gyoo
2017-01-01
This paper proposes a practical calibration solution for estimating the boresight and lever-arm parameters of the sensors mounted on a Mobile Mapping System (MMS). On our MMS devised for conducting the calibration experiment, three network video cameras, one mobile laser scanner, and one Global Navigation Satellite System (GNSS)/Inertial Navigation System (INS) were mounted. The geometric relationships between three sensors were solved by the proposed calibration, considering the GNSS/INS as one unit sensor. Our solution basically uses the point cloud generated by a 3-dimensional (3D) terrestrial laser scanner rather than using conventionally obtained 3D ground control features. With the terrestrial laser scanner, accurate and precise reference data could be produced and the plane features corresponding with the sparse mobile laser scanning data could be determined with high precision. Furthermore, corresponding point features could be extracted from the dense terrestrial laser scanning data and the images captured by the video cameras. The parameters of the boresight and the lever-arm were calculated based on the least squares approach and the precision of the boresight and lever-arm could be achieved by 0.1 degrees and 10 mm, respectively. PMID:28264457
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Transient extracellular glutamate events in the basolateral amygdala track reward seeking actions
Wassum, KM; Tolosa, VM; Tseng, TC; Balleine, BW; Monbouquette, HG; Maidment, NT
2012-01-01
The ability to make rapid, informed decisions about whether or not to engage in a sequence of actions to earn reward is essential for survival. Modeling in rodents has demonstrated a critical role for the basolateral amygdala (BLA) in such reward-seeking actions, but the precise neurochemical underpinnings are not well understood. Taking advantage of recent advancements in biosensor technologies, we made spatially discrete near-real time extracellular recordings of the major excitatory transmitter, glutamate, in the BLA of rats performing a self-paced lever-pressing sequence task for sucrose reward. This allowed us to detect rapid transient fluctuations in extracellular BLA glutamate time-locked to action performance. These glutamate transients tended to precede lever pressing actions and were markedly increased in frequency when rats were engaged in such reward seeking actions. Based on muscimol and tetrodotoxin microinfusions these glutamate transients appeared to originate from the terminals of neurons with cell bodies in the orbital frontal cortex. Importantly, glutamate transient amplitude and frequency fluctuated with the value of the earned reward and positively predicted lever pressing rate. Such novel rapid glutamate recordings during instrumental performance identify a role for glutamatergic signaling within the BLA in instrumental reward-seeking actions. PMID:22357857
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Paolone, Giovanna; Lee, Theresa M.; Sarter, Martin
2012-01-01
Although the impairments in cognitive performance that result from shifting or disrupting daily rhythms have been demonstrated, the neuronal mechanisms that optimize fixed time daily performance are poorly understood. We previously demonstrated that daily practice of a sustained attention task (SAT) evokes a diurnal activity pattern in rats. Here we report that SAT practice at a fixed time produced practice time-stamped increases in prefrontal cholinergic neurotransmission that persisted after SAT practice was terminated and in a different environment. SAT time-stamped cholinergic activation occurred irrespective of whether the SAT was practiced during the light or dark phase or in constant light conditions. In contrast, prior daily practice of an operant schedule of reinforcement, albeit generating more rewards and lever presses per session than the SAT, neither activated the cholinergic system nor affected the animals' nocturnal activity pattern. Likewise, food-restricted animals exhibited strong food anticipatory activity (FAA) and attenuated activity during the dark period but FAA was not associated with increases in prefrontal cholinergic activity. Removal of cholinergic neurons impaired SAT performance and facilitated the reemergence of nocturnality. Shifting SAT practice away from a fixed time resulted in significantly lower performance. In conclusion, these experiments demonstrated that fixed time, daily practice of a task assessing attention generates a precisely practice time-stamped activation of the cortical cholinergic input system. Time-stamped cholinergic activation benefits fixed time performance and, if practiced during the light phase, contributes to a diurnal activity pattern. PMID:22933795
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Paolone, Giovanna; Lee, Theresa M; Sarter, Martin
2012-08-29
Although the impairments in cognitive performance that result from shifting or disrupting daily rhythms have been demonstrated, the neuronal mechanisms that optimize fixed-time daily performance are poorly understood. We previously demonstrated that daily practice of a sustained attention task (SAT) evokes a diurnal activity pattern in rats. Here, we report that SAT practice at a fixed time produced practice time-stamped increases in prefrontal cholinergic neurotransmission that persisted after SAT practice was terminated and in a different environment. SAT time-stamped cholinergic activation occurred regardless of whether the SAT was practiced during the light or dark phase or in constant-light conditions. In contrast, prior daily practice of an operant schedule of reinforcement, albeit generating more rewards and lever presses per session than the SAT, neither activated the cholinergic system nor affected the animals' nocturnal activity pattern. Likewise, food-restricted animals exhibited strong food anticipatory activity (FAA) and attenuated activity during the dark phase but FAA was not associated with increases in prefrontal cholinergic activity. Removal of cholinergic neurons impaired SAT performance and facilitated the reemergence of nocturnality. Shifting SAT practice away from a fixed time resulted in significantly lower performance. In conclusion, these experiments demonstrated that fixed-time, daily practice of a task assessing attention generates a precisely practice time-stamped activation of the cortical cholinergic input system. Time-stamped cholinergic activation benefits fixed-time performance and, if practiced during the light phase, contributes to a diurnal activity pattern.
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Peciña, Susana; Schulkin, Jay; Berridge, Kent C
2006-04-13
Corticotropin-releasing factor (CRF) is typically considered to mediate aversive aspects of stress, fear and anxiety. However, CRF release in the brain is also elicited by natural rewards and incentive cues, raising the possibility that some CRF systems in the brain mediate an independent function of positive incentive motivation, such as amplifying incentive salience. Here we asked whether activation of a limbic CRF subsystem magnifies the increase in positive motivation for reward elicited by incentive cues previously associated with that reward, in a way that might exacerbate cue-triggered binge pursuit of food or other incentives? We assessed the impact of CRF microinjections into the medial shell of nucleus accumbens using a pure incentive version of Pavlovian-Instrumental transfer, a measure specifically sensitive to the incentive salience of reward cues (which it separates from influences of aversive stress, stress reduction, frustration and other traditional explanations for stress-increased behavior). Rats were first trained to press one of two levers to obtain sucrose pellets, and then separately conditioned to associate a Pavlovian cue with free sucrose pellets. On test days, rats received microinjections of vehicle, CRF (250 or 500 ng/0.2 microl) or amphetamine (20 microg/0.2 microl). Lever pressing was assessed in the presence or absence of the Pavlovian cues during a half-hour test. Microinjections of the highest dose of CRF (500 ng) or amphetamine (20 microg) selectively enhanced the ability of Pavlovian reward cues to trigger phasic peaks of increased instrumental performance for a sucrose reward, each peak lasting a minute or so before decaying after the cue. Lever pressing was not enhanced by CRF microinjections in the baseline absence of the Pavlovian cue or during the presentation without a cue, showing that the CRF enhancement could not be explained as a result of generalized motor arousal, frustration or stress, or by persistent attempts to ameliorate aversive states. We conclude that CRF in nucleus accumbens shell amplifies positive motivation for cued rewards, in particular by magnifying incentive salience that is attributed to Pavlovian cues previously associated with those rewards. CRF-induced magnification of incentive salience provides a novel explanation as to why stress may produce cue-triggered bursts of binge eating, drug addiction relapse, or other excessive pursuits of rewards.
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Peciña, Susana; Schulkin, Jay; Berridge, Kent C
2006-01-01
Background Corticotropin-releasing factor (CRF) is typically considered to mediate aversive aspects of stress, fear and anxiety. However, CRF release in the brain is also elicited by natural rewards and incentive cues, raising the possibility that some CRF systems in the brain mediate an independent function of positive incentive motivation, such as amplifying incentive salience. Here we asked whether activation of a limbic CRF subsystem magnifies the increase in positive motivation for reward elicited by incentive cues previously associated with that reward, in a way that might exacerbate cue-triggered binge pursuit of food or other incentives? We assessed the impact of CRF microinjections into the medial shell of nucleus accumbens using a pure incentive version of Pavlovian-Instrumental transfer, a measure specifically sensitive to the incentive salience of reward cues (which it separates from influences of aversive stress, stress reduction, frustration and other traditional explanations for stress-increased behavior). Rats were first trained to press one of two levers to obtain sucrose pellets, and then separately conditioned to associate a Pavlovian cue with free sucrose pellets. On test days, rats received microinjections of vehicle, CRF (250 or 500 ng/0.2 μl) or amphetamine (20 μg/0.2 μl). Lever pressing was assessed in the presence or absence of the Pavlovian cues during a half-hour test. Results Microinjections of the highest dose of CRF (500 ng) or amphetamine (20 μg) selectively enhanced the ability of Pavlovian reward cues to trigger phasic peaks of increased instrumental performance for a sucrose reward, each peak lasting a minute or so before decaying after the cue. Lever pressing was not enhanced by CRF microinjections in the baseline absence of the Pavlovian cue or during the presentation without a cue, showing that the CRF enhancement could not be explained as a result of generalized motor arousal, frustration or stress, or by persistent attempts to ameliorate aversive states. Conclusion We conclude that CRF in nucleus accumbens shell amplifies positive motivation for cued rewards, in particular by magnifying incentive salience that is attributed to Pavlovian cues previously associated with those rewards. CRF-induced magnification of incentive salience provides a novel explanation as to why stress may produce cue-triggered bursts of binge eating, drug addiction relapse, or other excessive pursuits of rewards. PMID:16613600
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Nucleus accumbens shell moderates preference bias during voluntary choice behavior.
Jang, Hyeran; Jung, Kanghoon; Jeong, Jaehoon; Park, Sang Ki; Kralik, Jerald D; Jeong, Jaeseung
2017-09-01
The nucleus accumbens (NAc) shell lies anatomically at a critical intersection within the brain's reward system circuitry, however, its role in voluntary choice behavior remains unclear. Rats with electrolytic lesions in the NAc shell were tested in a novel foraging paradigm. Over a continuous two-week period they freely chose among four nutritionally identical but differently flavored food pellets by pressing corresponding levers. We examined the lesion's effects on three behavioral dynamics components: motivation (when to eat), preference bias (what to choose) and persistence (how long to repeat the same choice). The lesion led to a marked increase in the preference bias: i.e., increased selection of the most-preferred choice option, and decreased selection of the others. We found no effects on any other behavioral measures, suggesting no effect on motivation or choice persistence. The results implicate the NAc shell in moderating the instrumental valuation process by inhibiting excessive bias toward preferred choice options. © The Author (2017). Published by Oxford University Press.
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Nucleus accumbens shell moderates preference bias during voluntary choice behavior
Jang, Hyeran; Jung, Kanghoon; Jeong, Jaehoon; Park, Sang Ki; Kralik, Jerald D.
2017-01-01
Abstract The nucleus accumbens (NAc) shell lies anatomically at a critical intersection within the brain’s reward system circuitry, however, its role in voluntary choice behavior remains unclear. Rats with electrolytic lesions in the NAc shell were tested in a novel foraging paradigm. Over a continuous two-week period they freely chose among four nutritionally identical but differently flavored food pellets by pressing corresponding levers. We examined the lesion’s effects on three behavioral dynamics components: motivation (when to eat), preference bias (what to choose) and persistence (how long to repeat the same choice). The lesion led to a marked increase in the preference bias: i.e., increased selection of the most-preferred choice option, and decreased selection of the others. We found no effects on any other behavioral measures, suggesting no effect on motivation or choice persistence. The results implicate the NAc shell in moderating the instrumental valuation process by inhibiting excessive bias toward preferred choice options. PMID:28992274
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From coprophagy to predation: a dung beetle that kills millipedes.
Larsen, Trond H; Lopera, Alejandro; Forsyth, Adrian; Génier, François
2009-04-23
The dung beetle subfamily Scarabaeinae is a cosmopolitan group of insects that feed primarily on dung. We describe the first case of an obligate predatory dung beetle and contrast its behaviour and morphology with those of its coprophagous sympatric congeners. Deltochilum valgum Burmeister killed and consumed millipedes in lowland rainforest in Peru. Ancestral ball-rolling behaviour shared by other canthonine species is abandoned, and the head, hind tibiae and pygidium of D. valgum are modified for novel functions during millipede predation. Millipedes were killed by disarticulation, often through decapitation, using the clypeus as a lever. Beetles killed millipedes much larger than themselves. In pitfall traps, D. valgum was attracted exclusively to millipedes, and preferred injured over uninjured millipedes. Morphological similarities placing D. valgum in the same subgenus with non-predatory dung-feeding species suggest a major and potentially rapid behavioural shift from coprophagy to predation. Ecological transitions enabling the exploitation of dramatically atypical niches, which may be more likely to occur when competition is intense, may help explain the evolution of novel ecological guilds and the diversification of exceptionally species-rich groups such as insects.
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Universal Design: A Step toward Successful Aging
Carr, Kelly; Weir, Patricia L.; Azar, Dory; Azar, Nadia R.
2013-01-01
The concept of aging successfully has become increasingly important as demographics shift towards an aging population. Successful aging has been defined to include (1) a low probability of disease and disease-related disability; (2) a high level of physical and cognitive functioning; and (3) an active engagement in life. The built environment can create opportunities or constraints for seniors to participate in social and productive activities. Universally designed spaces are more easily accessed and used by a spectrum of people without specialized adaptations. Thus, a universally designed environment creates opportunities for older adults to participate in these activities without the stigmatization associated with adapted or accessible designs. Providing older adults with specific universal design options (e.g., lever handle faucets) has the potential to increase the ease of completing activities of daily living, which promotes a continual engagement in life. Literature regarding universal design is promising; however, its theory requires further attention from professionals designing the built environment, evidence of the significance of its application from academics, and the embracement of its core principles from society. Overall, universal design has the potential to provide a stepping stone toward successful aging. PMID:23431446
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The power dynamics perpetuating unsafe abortion in Africa: a feminist perspective.
Braam, Tamara; Hessini, Leila
2004-04-01
Tens of thousands of African women die every year because societies and governments either ignore the issue of unsafe abortion or actively refuse to address it. This paper explores the issue of abortion from a feminist perspective, centrally arguing that finding appropriate strategies to reclaim women's power at an individual and social level is a central lever for developing effective strategies to increase women's access to safe abortion services. The paper emphasises the central role of patriarchy in shaping the ways power plays itself out in individual relationships, and at social, economic and political levels. The ideology of male superiority denies abortion as an important issue of status and frames the morality, legality and socio-cultural attitudes towards abortion. Patriarchy sculpts unequal gender power relationships and takes power away from women in making decisions about their bodies. Other forms of power such as economic inequality, discourse and power within relationships are also explored. Recommended solutions to shifting the power dynamics around the issue include a combination of public health, rights-based, legal reform and social justice approaches.
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(-)Ephedrine and caffeine mutually potentiate one another's amphetamine-like stimulus effects.
Young, R; Gabryszuk, M; Glennon, R A
1998-10-01
Using rats trained to discriminate 1 mg/kg of (+)amphetamine (ED50 = 0.4 mg/kg) from saline vehicle in a two-lever drug discrimination procedure, it was shown that (-)ephedrine (ED50 = 4.5 mg/kg), but not (+)ephedrine, substitutes for the (+)AMPH stimulus. It was also shown that caffeine (ED50 = 12.9 mg/kg) can substitute for (+)amphetamine in a dose-related fashion. Doses of (-)ephedrine and caffeine, which produced < or = 1% drug-appropriate responding when administered alone, were able to enhance each other's stimulus effects when administered in combination such that there was a twofold leftward shift in their respective dose-response curves. Furthermore, stimulus generalization occurred when a dose of caffeine that produced saline-appropriate responding when administered alone was administered in combination with (+)ephedrine. It would appear that low doses of (-)ephedrine and caffeine may mutually potentiate one another's stimulus effects in (+)AMPH-trained rats, and that a combination of caffeine and (+)ephedrine result in altered stimulus character when compared to comparable doses of either agent administered alone.
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Disrupting reconsolidation: memory erasure or blunting of emotional/motivational value?
Cogan, Elizabeth S; Shapses, Mark A; Robinson, Terry E; Tronson, Natalie C
2018-05-03
When memories are retrieved they become labile, and subject to alteration by a process known as reconsolidation. Disruption of memory reconsolidation decreases the performance of learned responses, which is often attributed to erasure of the memory; in the case of Pavlovian learning, to a loss of the association between a conditioned stimulus (CS) and unconditioned stimulus (US). However, an alternative interpretation is that disrupting reconsolidation does not erase memories, but blunts their emotional/motivational impact. It is difficult to parse the predictive vs. emotional/motivational value of CSs in non-human animals, but studies on variation in the form of conditioned responses (CRs) in a Pavlovian conditioned approach task suggest a way to do this. In this task a lever-CS paired with a food reward (US) acquires predictive value in all rats, but is attributed with emotional/motivational value to a greater extent in some rats (sign-trackers) than others (goal-trackers). We report that the post-retrieval administration of propranolol selectively attenuates a sign-tracking CR, and the associated neural activation of brain "motive circuits", while having no effect on conditioned orienting behavior in sign-trackers, or on goal-tracking CRs evoked by either a lever-CS or a tone-CS. We conclude that the disruption of reconsolidation by post-retrieval propranolol degrades the emotional/motivational impact of the CS, required for sign-tracking, but leaves the CS-US association intact. The possibility that post-retrieval interventions can reduce the emotional/motivational aspects of memories, without actually erasing them, has important implications for treating maladaptive memories that contribute to some psychiatric disorders.
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Anterior cingulate cortex supports effort allocation towards a qualitatively preferred option.
Hart, Evan E; Gerson, Julian O; Zoken, Yael; Garcia, Marisella; Izquierdo, Alicia
2017-07-01
The anterior cingulate cortex (ACC) is known to be involved in effortful choice, yet its role in cost-benefit evaluation of qualitatively different rewards (more/less preferred), beyond magnitude differences (larger/smaller), is poorly understood. Selecting between qualitatively different options is a decision type commonly faced by humans. Here, we assessed the role of ACC on a task that has primarily been used to probe striatal function in motivation. Rats were trained to stable performance on a progressive ratio schedule for sucrose pellets and were then given sham surgeries (control) or excitotoxic NMDA lesions of ACC. Subsequently, a choice was introduced: chow was concurrently available while animals could work for the preferred sucrose pellets. ACC lesions produced a significant decrease in lever presses for sucrose pellets compared to control, whereas chow consumption was unaffected. Lesions had no effect on sucrose pellet preference when both options were freely available. When laboratory chow was not concurrently available, ACC-lesioned rats exhibited similar lever pressing as controls. During a test under specific satiety for sucrose pellets, ACC-lesioned rats also showed intact devaluation effects. The effects of ACC lesions in our task are not mediated by decreased appetite, a change in food preference, a failure to update value or a learning deficit. Taken together, we found that ACC lesions decreased effort for a qualitatively preferred option. These results are discussed with reference to effects of striatal manipulations and our recent report of a role for basolateral amygdala in effortful choice. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.
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Morphologic Variability of the Shoulder between the Populations of North American and East Asian
Cabezas, Andres F.; Krebes, Kristi; Hussey, Michael M.; Santoni, Brandon G.; Kim, Hyuong Sik
2016-01-01
Background The aim of this study was to determine if there were significant differences in glenohumeral joint morphology between North American and East Asian populations that may influence sizing and selection of shoulder arthroplasty systems. Methods Computed tomography reconstructions of 92 North American and 58 East Asian patients were used to perform 3-dimensional measurements. The proximal humeral position was normalized in all patients by aligning it with the scapular plane utilizing anatomic landmarks. Measurements were performed on the humerus and scapula and included coronal and axial humeral head radius, humeral neck shaft and articular arc angles, glenoid height and width, and critical shoulder angle. Glenohumeral relationships were also measured and included lateral distance to the greater tuberosity and acromion, abduction lever arm, and acromial index. Parametric and nonparametric statistical analyses were used to compare population metrics. Results East Asian glenohumeral measurements were significantly smaller for all linear metrics (p < 0.05), with the exception of acromial length, which was greater than in the North American cohort (p < 0.001). The increase in acromial length affected all measurements involving the acromion including abduction lever arms. No difference was found between the neck shaft and articular angular measurements. Conclusions The East Asian population exhibited smaller shoulder morphometrics than their North American cohort, with the exception of an extended acromial overhang. The morphologic data can provide some additional factors to consider when choosing an optimal shoulder implant for the East Asian population, in addition to creating future designs that may better accommodate this population. PMID:27583111
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Caspari, Natalie; Arsenault, John T; Vandenberghe, Rik; Vanduffel, Wim
2018-06-01
We continually shift our attention between items in the visual environment. These attention shifts are usually based on task relevance (top-down) or the saliency of a sudden, unexpected stimulus (bottom-up), and are typically followed by goal-directed actions. It could be argued that any species that can covertly shift its focus of attention will rely on similar, evolutionarily conserved neural substrates for processing such shift-signals. To address this possibility, we performed comparative fMRI experiments in humans and monkeys, combining traditional, and novel, data-driven analytical approaches. Specifically, we examined correspondences between monkey and human brain areas activated during covert attention shifts. When "shift" events were compared with "stay" events, the medial (superior) parietal lobe (mSPL) and inferior parietal lobes showed similar shift sensitivities across species, whereas frontal activations were stronger in monkeys. To identify, in a data-driven manner, monkey regions that corresponded with human shift-selective SPL, we used a novel interspecies beta-correlation strategy whereby task-related beta-values were correlated across voxels or regions-of-interest in the 2 species. Monkey medial parietal areas V6/V6A most consistently correlated with shift-selective human mSPL. Our results indicate that both species recruit corresponding, evolutionarily conserved regions within the medial superior parietal lobe for shifting spatial attention.
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Oscillator circuit for use with high loss quartz resonator sensors
Wessendorf, Otto
1995-01-01
The disclosure is directed to a Lever oscillator for use in high resistance resonator applications, especially for use with quartz resonator sensors. The oscillator is designed to operate over a wide dynamic range of resonator resistance due to damping of the resonator in mediums such as liquids. An oscillator design is presented that allows both frequency and loss (R.sub.m) of the resonator to be determined over a wide dynamic range of resonator loss. The Lever oscillator uses negative feedback in a differential amplifier configuration to actively and variably divide (or leverage) the resonator impedance such that the oscillator can maintain the phase and gain of the loop over a wide range of resonator resistance.
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Hand sanitizer dispensers and associated hospital-acquired infections: friend or fomite?
Eiref, Simon D; Leitman, I Michael; Riley, William
2012-06-01
Waterless alcohol-based hand sanitizers are an increasingly popular method of hand hygiene and help prevent hospital-acquired infection (HAI). Whether hand sanitizer dispensers (HSDs) may themselves harbor pathogens or act as fomites has not been reported. All HSDs in the surgical intensive care unit of an urban teaching hospital were cultured at three sites: The dispenser lever, the rear underside, and the area surrounding the dispensing nozzle. All HSDs yielded one or more bacterial species, including commensal skin flora and enteric gram-negative bacilli. Colonization was greatest on the lever, where there is direct hand contact. Hand sanitizer dispensers can become contaminated with pathogens that cause HAI and thus are potential fomites.
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Viscous cavity damping of a microlever in a simple fluid.
Siria, A; Drezet, A; Marchi, F; Comin, F; Huant, S; Chevrier, J
2009-06-26
We consider the problem of oscillation damping in air of a thermally actuated microlever as it gradually approaches an infinite wall in parallel geometry. As the gap is decreased from 20 microm down to 400 nm, we observe the increasing damping of the lever Brownian motion in the fluid laminar regime. This manifests itself as a linear decrease in the lever quality factor accompanied by a dramatic softening of its resonance, and eventually leads to the freezing of the CL oscillation. We are able to quantitatively explain this behavior by analytically solving the Navier-Stokes equation with perfect slip boundary conditions. Our findings may have implications for microfluidics and micro- and nanoelectromechanical applications.
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39. CLOSE UP DETAIL OF THE FEEDER AND STAMP CONNECTION. ...
39. CLOSE UP DETAIL OF THE FEEDER AND STAMP CONNECTION. THE STAMP AN MORTAR BOX ARE ON THE LEFT AND THE FEEDER WITH ITS FEEDER DISK IS ON THE RIGHT. NOTE THE COLLAR ON THE CENTER STAMP STEM (UPPER LEFT CORNER OF THE IMAGE) THAT ACTIVATES THE LEVER IN THE CENTER OF THE PHOTO. THE COLLAR IS POSITIONED SUCH THAT WHEN THE LEVEL OF THE MATERIAL REACHES A LOW POINT IN THE MORTAR BOX IT PUSHES DOWN ON THE LEVER WHICH IN TURN ACTIVATES THE AUTOMATIC FEEDER DRIVE MECHANISM WHICH THEM DELIVERS ORE INTO THE BACKSIDE OF THE MORTAR BOX. - Standard Gold Mill, East of Bodie Creek, Northeast of Bodie, Bodie, Mono County, CA
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Long-range coupling between ATP-binding and lever-arm regions in myosin via dielectric allostery
NASA Astrophysics Data System (ADS)
Sato, Takato; Ohnuki, Jun; Takano, Mitsunori
2017-12-01
A protein molecule is a dielectric substance, so the binding of a ligand is expected to induce dielectric response in the protein molecule, considering that ligands are charged or polar in general. We previously reported that binding of adenosine triphosphate (ATP) to molecular motor myosin actually induces such a dielectric response in myosin due to the net negative charge of ATP. By this dielectric response, referred to as "dielectric allostery," spatially separated two regions in myosin, the ATP-binding region and the actin-binding region, are allosterically coupled. In this study, from the statistically stringent analyses of the extensive molecular dynamics simulation data obtained in the ATP-free and the ATP-bound states, we show that there exists the dielectric allostery that transmits the signal of ATP binding toward the distant lever-arm region. The ATP-binding-induced electrostatic potential change observed on the surface of the main domain induced a movement of the converter subdomain from which the lever arm extends. The dielectric response was found to be caused by an underlying large-scale concerted rearrangement of the electrostatic bond network, in which highly conserved charged/polar residues are involved. Our study suggests the importance of the dielectric property for molecular machines in exerting their function.
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A Conformational Transition in the Myosin VI Converter Contributes to the Variable Step Size
Ovchinnikov, V.; Cecchini, M.; Vanden-Eijnden, E.; Karplus, M.
2011-01-01
Myosin VI (MVI) is a dimeric molecular motor that translocates backwards on actin filaments with a surprisingly large and variable step size, given its short lever arm. A recent x-ray structure of MVI indicates that the large step size can be explained in part by a novel conformation of the converter subdomain in the prepowerstroke state, in which a 53-residue insert, unique to MVI, reorients the lever arm nearly parallel to the actin filament. To determine whether the existence of the novel converter conformation could contribute to the step-size variability, we used a path-based free-energy simulation tool, the string method, to show that there is a small free-energy difference between the novel converter conformation and the conventional conformation found in other myosins. This result suggests that MVI can bind to actin with the converter in either conformation. Models of MVI/MV chimeric dimers show that the variability in the tilting angle of the lever arm that results from the two converter conformations can lead to step-size variations of ∼12 nm. These variations, in combination with other proposed mechanisms, could explain the experimentally determined step-size variability of ∼25 nm for wild-type MVI. Mutations to test the findings by experiment are suggested. PMID:22098742
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Effects of exposure to 56Fe particles or protons on fixed-ratio operant responding in rats
NASA Technical Reports Server (NTRS)
Rabin, Bernard M.; Buhler, Lynn L.; Joseph, James A.; Shukitt-Hale, Barbara; Jenkins, Daniel G.
2002-01-01
On long-duration trips outside of the magnetosphere, astronauts will be exposed to protons and to heavy particles which can affect their performance of required tasks. It is essential to determine the range of behaviors that might be affected by exposure to these types of radiation in order to understand the nature of behavioral deficits and to develop effective countermeasures. The present experiment examined the ability of rats to make an operant response following exposure to protons (250 MeV, 4 Gy) or 56Fe particles (1 GeV/n, 1 or 2 Gy). Following irradiation, rats were trained to press a lever in order to obtain food reinforcement. They were then placed on an ascending fixed-ratio schedule from FR-1 (each lever press rewarded with a food pellet) through FR-35 (35 lever presses required for 1 food pellet). Rats exposed to 4 Gy of protons or 1 Gy of 56Fe particles responded similarly to controls, increasing their rate of responding as the ratio increased. However, rats exposed to 2 Gy of 56Fe particles failed to increase their rate of responding at ratios greater than FR-20, indicating that rats exposed to 2 Gy of 56Fe particles cannot respond appropriately to increasing work requirements.
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Corticospinal signals recorded with MEAs can predict the volitional forearm forces in rats.
Guo, Yi; Mesut, Sahin; Foulds, Richard A; Adamovich, Sergei V
2013-01-01
We set out to investigate if volitional components in the descending tracts of the spinal cord white matter can be accessed with multi-electrode array (MEA) recording technique. Rats were trained to press a lever connected to a haptic device with force feedback to receive sugar pellets. A flexible-substrate multi-electrode array was chronically implanted into the dorsal column of the cervical spinal cord. Field potentials and multi-unit activities were recorded from the descending axons of the corticospinal tract while the rat performed a lever pressing task. Forelimb forces, recorded with the sensor attached to the lever, were reconstructed using the hand position data and the neural signals through multiple trials over three weeks. The regression coefficients found from the trial set were cross-validated on the other trials recorded on same day. Approximately 30 trials of at least 2 seconds were required for accurate model estimation. The maximum correlation coefficient between the actual and predicted force was 0.7 in the test set. Positional information and its interaction with neural signals improved the correlation coefficient by 0.1 to 0.15. These results suggest that the volitional information contained in the corticospinal tract can be extracted with multi-channel neural recordings made with parenchymal electrodes.
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Unrevealed part of myosin's powerstroke accounts for high efficiency of muscle contraction.
Bibó, András; Károlyi, György; Kovács, Mihály
2017-09-01
Myosin II, the motor protein driving muscle contraction, uses energy of ATP hydrolysis to produce movement along actin. The key step of energy transduction is the powerstroke, involving rotation of myosin's lever while myosin is attached to actin. Macroscopic measurements indicated high thermodynamic efficiency for energy conversion. However, single-molecule experiments indicated lower efficiency, provoking a long-standing discrepancy. Based on the Fluctuation-Dissipation Theorem, we built a sufficiently detailed but low degree-of-freedom model reconstructing the entire mechanoenzymatic cycle. We show that a high axial stiffness of the lever during an initial, experimentally yet unrevealed part of the powerstroke results in a short-time, ratchet-like Kramers effect, and is responsible for the missing efficiency. The second part of the powerstroke is an Eyring-like relaxation that dominantly contributes to lever rotation, but produces only a minor part of the work. The model reveals the structural background of myosin's capability to function as a robust molecular engine and a very precise load sensor as well. Our model also suggests an explanation for the malfunction of myosins harboring mutations that lead to hypertrophic cardiomyopathies with most severe clinical prognosis. The model explains how a force-transmitting device within a biological motor can enable high energetic efficiency. Copyright © 2017 Elsevier B.V. All rights reserved.
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See, R E; Grimm, J W; Kruzich, P J; Rustay, N
1999-11-01
Previous studies have demonstrated that conditioned stimuli can increase responding on a drug-associated lever after extinction from drug self-administration. The present study investigated singular stimuli (tone or light) or a compound stimulus (tone + light) for their ability to increase extinguished responding following chronic cocaine self-administration. Rats self-administered cocaine for 2 weeks on a fixed ratio (FR1) schedule of reinforcement, in which lever responding resulted in varied presentation of a tone, light, or tone + light combination. The rats were then exposed to 1 week of daily extinction sessions. Presentation of the tone + light on day 8 of extinction in the absence of cocaine reinforcement resulted in a significant increase in responding, while either stimulus component alone was much weaker or failed to produce any changes from extinction rates of responding. In addition, changing the duration of the single elements of the compound did not affect the magnitude of increased responding to the compound. Following three final extinction sessions, robust lever responding for cocaine infusions on day 12 of extinction was seen across all groups. These findings suggest that compound stimuli may be critical to fully activate drug-seeking behavior in conditions of craving and relapse following prolonged extinction.
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Visualizing Key Hinges and a Potential Major Source of Compliance in the Lever Arm of Myosin
DOE Office of Scientific and Technical Information (OSTI.GOV)
J Brown; V Senthil Kumar; E ONeall-Hennessey
2011-12-31
We have determined the 2.3-{angstrom}-resolution crystal structure of a myosin light chain domain, corresponding to one type found in sea scallop catch ('smooth') muscle. This structure reveals hinges that may function in the 'on' and 'off' states of myosin. The molecule adopts two different conformations about the heavy chain 'hook' and regulatory light chain (RLC) helix D. This conformational change results in extended and compressed forms of the lever arm whose lengths differ by 10 {angstrom}. The heavy chain hook and RLC helix D hinges could thus serve as a potential major and localized source of cross-bridge compliance during themore » contractile cycle. In addition, in one of the molecules of the crystal, part of the RLC N-terminal extension is seen in atomic detail and forms a one-turn alpha-helix that interacts with RLC helix D. This extension, whose sequence is highly variable in different myosins, may thus modulate the flexibility of the lever arm. Moreover, the relative proximity of the phosphorylation site to the helix D hinge suggests a potential role for conformational changes about this hinge in the transition between the on and off states of regulated myosins.« less
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Visualizing key hinges and a potential major source of compliance in the lever arm of myosin
DOE Office of Scientific and Technical Information (OSTI.GOV)
Brown, J.H.; Robinson, H.; Senthil Kumar, V. S.
2011-01-04
We have determined the 2.3-{angstrom}-resolution crystal structure of a myosin light chain domain, corresponding to one type found in sea scallop catch ('smooth') muscle. This structure reveals hinges that may function in the 'on' and 'off' states of myosin. The molecule adopts two different conformations about the heavy chain 'hook' and regulatory light chain (RLC) helix D. This conformational change results in extended and compressed forms of the lever arm whose lengths differ by 10 {angstrom}. The heavy chain hook and RLC helix D hinges could thus serve as a potential major and localized source of cross-bridge compliance during themore » contractile cycle. In addition, in one of the molecules of the crystal, part of the RLC N-terminal extension is seen in atomic detail and forms a one-turn alpha-helix that interacts with RLC helix D. This extension, whose sequence is highly variable in different myosins, may thus modulate the flexibility of the lever arm. Moreover, the relative proximity of the phosphorylation site to the helix D hinge suggests a potential role for conformational changes about this hinge in the transition between the on and off states of regulated myosins.« less
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Krank, Marvin D
2003-10-01
Conditioned incentive theories of addictive behavior propose that cues signaling a drug's reinforcing effects activate a central motivational state. Incentive motivation enhances drug-taking and drug-seeking behavior. We investigated the behavioral response to cues associated with ethanol and their interaction with operant self-administration of ethanol. In two experiments, rats received operant training to press a lever for a sweetened ethanol solution. After operant training, the animals were given Pavlovian pairings of a brief and localized cue light with the sweetened ethanol solution (no lever present). Lever pressing for ethanol was then re-established, and the behavioral effects of the cue light were tested during an ethanol self-administration session. The conditioned responses resulting from pairing cue lights with the opportunity to ingest ethanol had three main effects: (1) induction of operant behavior reinforced by ethanol, (2) stimulation of ethanol-seeking behavior (magazine entries), and (3) signal-directed behavior (i.e., autoshaping, or sign-tracking). Signal-directed behavior interacted with the other two effects in a manner predicted by the location of the cue light. These conditioned responses interact with operant responding for ethanol reinforcement. These findings demonstrate the importance of Pavlovian conditioning effects on ethanol self-administration and are consistent with conditioned incentive theories of addictive behavior.
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Natsubori, Akiyo; Tsutsui-Kimura, Iku; Nishida, Hiroshi; Bouchekioua, Youcef; Sekiya, Hiroshi; Uchigashima, Motokazu; Watanabe, Masahiko; de Kerchove d'Exaerde, Alban; Mimura, Masaru; Takata, Norio; Tanaka, Kenji F
2017-03-08
The ventral striatum is involved in motivated behavior. Akin to the dorsal striatum, the ventral striatum contains two parallel pathways: the striatomesencephalic pathway consisting of dopamine receptor Type 1-expressing medium spiny neurons (D1-MSNs) and the striatopallidal pathway consisting of D2-MSNs. These two genetically identified pathways are thought to encode opposing functions in motivated behavior. It has also been reported that D1/D2 genetic selectivity is not attributed to the anatomical discrimination of two pathways. We wanted to determine whether D1- and D2-MSNs in the ventral striatum functioned in an opposing manner as previous observations claimed, and whether D1/D2 selectivity corresponded to a functional segregation in motivated behavior of mice. To address this question, we focused on the lateral portion of ventral striatum as a region implicated in food-incentive, goal-directed behavior, and recorded D1 or D2-MSN activity by using a gene-encoded ratiometric Ca 2+ indicator and by constructing a fiberphotometry system, and manipulated their activities via optogenetic inhibition during ongoing behaviors. We observed concurrent event-related compound Ca 2+ elevations in ventrolateral D1- and D2-MSNs, especially at trial start cue-related and first lever press-related times. D1 or D2 selective optogenetic inhibition just after the trial start cue resulted in a reduction of goal-directed behavior, indicating a shared coding of motivated behavior by both populations at this time. Only D1-selective inhibition just after the first lever press resulted in the reduction of behavior, indicating D1-MSN-specific coding at that specific time. Our data did not support opposing encoding by both populations in food-incentive, goal-directed behavior. SIGNIFICANCE STATEMENT An opposing role of dopamine receptor Type 1 or Type 2-expressing medium spiny neurons (D1-MSNs or D2-MSNs) on striatum-mediated behaviors has been widely accepted. However, this idea has been questioned by recent reports. In the present study, we measured concurrent Ca 2+ activity patterns of D1- and D2-MSNs in the ventrolateral striatum during food-incentive, goal-directed behavior in mice. According to Ca 2+ activity patterns, we conducted timing-specific optogenetic inhibition of each type of MSN. We demonstrated that both D1- and D2-MSNs in the ventrolateral striatum commonly and positively encoded action initiation, whereas only D1-MSNs positively encoded sustained motivated behavior. These findings led us to reconsider the prevailing notion of a functional segregation of MSN activity in the ventral striatum. Copyright © 2017 the authors 0270-6474/17/372724-11$15.00/0.
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Maccioni, Paola; Colombo, Giancarlo; Lorrai, Irene; Zaru, Alessandro; Carai, Mauro A M; Gessa, Gian Luigi; Brizzi, Antonella; Mugnaini, Claudia; Corelli, Federico
2017-09-01
COR659 [methyl2-(4-chlorophenylcarboxamido)-4-ethyl-5-methylthiophene-3-carboxylate] is a new, positive allosteric modulator (PAM) of the GABA B receptor. This study evaluated whether COR659 shared with previously tested GABA B PAMs the capacity to reduce alcohol self-administration in rats. Treatment with non-sedative doses of COR659 (2.5, 5, and 10 mg/kg; i.p.) suppressed lever-responding for alcohol (15% v/v) in Sardinian alcohol-preferring (sP) rats under the fixed ratio (FR) 4 (FR4) and progressive ratio (PR) schedules of reinforcement; COR659 was more potent and effective than the reference GABA B PAM, GS39783. Treatment with COR659, but not GS39783, suppressed (a) lever-responding for a sucrose solution (1-3% w/v) in sP rats under the FR4 and PR schedules, (b) lever-responding for a chocolate solution [5% (w/v) Nesquik®] in Wistar rats under the FR10 and PR schedules, and (c) cue-induced reinstatement of chocolate seeking in Wistar rats. Treatment with COR659 was completely ineffective on lever-responding (FR10) for regular food pellets in food-deprived Wistar rats. Pretreatment with the GABA B receptor antagonist, SCH50911, partially blocked COR659-induced reduction of alcohol self-administration, being ineffective on reduction of chocolate self-administration. Pretreatment with the cannabinoid CB 1 receptor antagonist, AM4113, fully blocked COR659-induced reduction of chocolate self-administration, being ineffective on reduction of alcohol self-administration. COR659 might exert its behavioral effects via a composite mechanism: (i) positive allosteric modulation of the GABA B receptor, responsible for a large proportion of reduction of alcohol self-administration; (ii) an action at other receptor system(s), including the cannabinoid CB 1 receptor, through which COR659 affects seeking and consumption of highly palatable foods.
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Piantadosi, Patrick T; Yeates, Dylan C M; Wilkins, Mathew; Floresco, Stan B
2017-04-01
The involvement of different nodes within meso-cortico-limbic-striatal circuitry in mediating reward-seeking has been well described, yet comparatively less is known about how such circuitry may regulate appetitively-motivated behaviors that may be punished. The basolateral amygdala (BLA) is one nucleus that has been implicated in suppressing punished reward-seeking, and this structure can modulate goal-directed behavior via projections to subregions of the nucleus accumbens (NAc). Here, we examined the effects of reversible inactivations of the BLA, NAc Shell (NAcS), and core (NAcC) on performance of a "Conflict" task where rats pressed a lever for sucrose reinforcement during three distinct 5min phases. During the first and last phases of a session, rats lever-pressed for food reward delivered on a VI-15/FR5 schedule. In between these phases was a signaled "Conflict" period, where each lever-press yielded food, but 50% of presses were also punished with foot-shock. Under control conditions, well-trained rats responded vigorously during the two "safe" VI-15/FR5 periods, but reduced responding during the punished Conflict period. Inactivation of either the BLA or the NAcS via infusions of baclofen/muscimol disinhibited punished seeking, increasing lever-pressing during the conflict period, while attenuating pressing during VI-15/FR5 phases. In contrast, NAcC inactivation markedly decreased responding across all three phases. Similar inactivation of the BLA or NAcS did not alter responding in a separate control experiment where rats pressed for food on schedules identical to the Conflict task in the absence of any punishment, while NAcC inactivation again suppressed responding. These results imply that BLA and NAcS are part of a circuit that suppresses reward-seeking in the face of danger, which in turn may have implications for disorders characterized by punishment resistance, including substance abuse and obsessive-compulsive disorder. Copyright © 2017 Elsevier Inc. All rights reserved.
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Evans, Drew R; Craig, Vincent S J
2006-03-23
Cantilever beams, both microscopic and macroscopic, are used as sensors in a great variety of applications. An optical lever system is commonly employed to determine the deflection and thereby the profile of the cantilever under load. The sensitivity of the optical lever must be calibrated, and this is usually achieved by application of a known load or deflection to the free end of the cantilever. When the sensing operation involves a different type of load or a combination of types of loadings, the calibration and the deflection values derived from it become invalid. Here we develop a master equation that permits the true deflection of the cantilever to be obtained simply from the measurement of the apparent deflection for uniformly distributed loadings and end-moment loadings. These loadings are relevant to the uniform adsorption or application of material to the cantilever or the application of a surface stress to the cantilever and should assist experimentalists using the optical lever, such as in the atomic force microscope, to measure cantilever deflections in a great variety of sensing applications. We then apply this treatment to the experimental evaluation of surface stress. Three forms of Stoney's equation that relate the apparent deflection to the surface stress, which is valid for both macroscopic and microscopic experiments, are derived. Analysis of the errors arising from incorrect modeling of the loading conditions of the cantilever currently applied in experiments is also presented. It is shown that the reported literature values for surface stress in microscopic experiments are typically 9% smaller than their true value. For macroscopic experiments, we demonstrate that the added mass of the film or coating generally dominates the measured deflection and must be accounted for accurately if surface stress measurements are to be made. Further, the reported measurements generally use a form of Stoney's equation that is in error, resulting in an overestimation of surface stress by a factor >5.
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REINSTATEMENT OF ETHANOL AND SUCROSE SEEKING BY THE NEUROSTEROID ALLOPREGNANOLONE IN C57BL/6 MICE
Finn, Deborah A.; Mark, Gregory P.; Fretwell, Andrea M.; Gililland, Katherine R.; Strong, Moriah N.; Ford, Matthew M.
2016-01-01
Rationale Recent work in our laboratory documented that the “sipper” method of operant ethanol self-administration produced high ethanol intake and blood ethanol concentrations as well as the typical extinction “burst” in responding under non-reinforced conditions in male C57BL/6 mice. However, the neurochemical basis for reinstatement of responding following extinction has not been examined in mice with this model. Objectives Based on findings that the GABAergic neurosteroid allopregnanolone (ALLO) significantly increased the consummatory phase of ethanol self-administration, the present study determined the effect of ALLO on reinstatement of extinguished ethanol-seeking behavior and compared this effect to reinstatement of responding for sucrose reward. Methods Separate groups of male C57BL/6 mice were trained to lever press for access to a 10% ethanol (10E) or a 5% sucrose (5S) solution. A single response requirement of 16 presses (RR16) on an active lever resulted in 30 min of continuous access to the 10E or 5S solution. After the animals responded on the RR16 schedule for 14 weeks, mice were exposed to 30 min extinction sessions where responding had no scheduled consequence. Once responding stabilized below the pre-extinction baseline, mice received an IP injection of ALLO (0, 3.2, 5.6, 10 or 17 mg/kg) 15 min prior to the extinction session in a within-subjects design. Results ALLO produced a dose-dependent increase in responding under non-reinforced conditions in both the 10E and 5S groups. Additional work documented the ability of a conditioned cue light or a compound cue (light+lever retraction) to reinstate non-reinforced responding on the previously active lever. Conclusions These findings definitively show that conditioned cues and priming with ALLO are potent stimuli for reinstating both ethanol and sucrose seeking behavior in C57BL/6 mice. PMID:18758755
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Primary selection into shift work and change of cardiovascular risk profile.
Yong, Mei; Germann, Christina; Lang, Stefan; Oberlinner, Christoph
2015-05-01
A potential "healthy shift worker effect" may bias the studied effect of shift work on health. The observed differences among shift and day workers in health behavior and health outcomes can be caused by: (i) primary selection, (ii) the influence from the shift work-related environment, and (iii) the impact of shift work. We aimed to study these potential sources. A cohort of 4754 male trainees who had finished their professional training and started their career in production in a chemical company between 1995 and 2012 was identified. Among them, 1348 (28%) were involved in rotating shift work and 3406 (72%) in day work. Information on health behavior and risk factors for cardiovascular diseases was retrieved from the medical examinations. This information was then compared (i) at the beginning of training, (ii) at the end of training, and (iii) 3 years after the employment, in relation to the working time. At the beginning of the training, the prevalence of smokers was higher among future shift workers (26% versus 21%), from 1995 to 2012. During the training and the first three years of employment, a marginal decline of systolic blood pressure and an elevation of triglyceride were related with shift work. No difference was found with respect to other risk factors for cardiovascular diseases. Our findings do not support a primary selection in favor of shift workers. An impact of shift work on the risk profile of cardiovascular diseases was not indicated in the observation period.
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Simultaneous weak measurement of angular and spatial Goos-Hänchen and Imbert-Fedorov shifts
NASA Astrophysics Data System (ADS)
Prajapati, Chandravati; Viswanathan, Nirmal K.
2017-10-01
We propose and demonstrate the weak measurement scheme to simultaneously measure the amplified angular and spatial contributions to the Goos-Hänchen (GH) and Imbert-Fedorov (IF) shifts, due to transmission through a glass plate. We have studied two cases of post-selection using a polarizer in the first case and a quarter-wave plate (QWP)-polarizer combination in the second case. The two cases are analyzed theoretically using Jones calculus of polarization formalism and the results are verified experimentally. In the first case of post-selection, the projection of the polarizer at +/- {{Δ }} away from the crossed position amplifies the angular GH and IF shifts, while in the second case of post-selection, the projection of QWP at +/- {{Δ }} and polarizer kept fixed measures the polarization ellipticity in the beam and thus amplifies the spatial shift along with the angular shift simultaneously, for {{Δ }}\\ll 1.
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Xue, Ying; Intrator, Orna
2016-02-01
The evolving role of nurse practitioners (NPs) as primary care providers, especially for vulnerable populations, is central to the debate regarding strategies to address the growing need for primary care services. The current article provides policy recommendations for leveraging and expanding the historic role of NPs in caring for vulnerable populations, by focusing on three key policy levers: NP scope-of-practice regulation, distribution of the NP workforce, and NP education. These policy levers must go hand in hand to build a sufficient and equitably distributed NP workforce, to help meet the escalating need for primary care in an era of health-care reform. © The Author(s) 2016.
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Effects of extinction in multiple contexts on renewal of instrumental responses.
Bernal-Gamboa, Rodolfo; Nieto, Javier; Uengoer, Metin
2017-09-01
In two experiments with rats, we investigated the effects of using multiple contexts during extinction on renewal of lever-pressing behavior. During the first phase of both experiments, rats were reinforced to press a lever for food in Context A. Then, responses underwent extinction. For half of the animals, extinction sessions were conducted in a single context, whereas the other half received extinction in three different contexts. In Experiment 1, we observed that extinction in multiple contexts eliminated ABC renewal, but had no detectable impact on ABA renewal. Experiment 2 revealed that conducting extended extinction training in multiple contexts attenuated ABA renewal. Theoretical and clinical implications of the present findings are discussed. Copyright © 2017 Elsevier B.V. All rights reserved.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Torun, H.; Torello, D.; Degertekin, F. L.
2011-08-15
The authors describe a method of actuation for atomic force microscope (AFM) probes to improve imaging speed and displacement range simultaneously. Unlike conventional piezoelectric tube actuation, the proposed method involves a lever and fulcrum ''seesaw'' like actuation mechanism that uses a small, fast piezoelectric transducer. The lever arm of the seesaw mechanism increases the apparent displacement range by an adjustable gain factor, overcoming the standard tradeoff between imaging speed and displacement range. Experimental characterization of a cantilever holder implementing the method is provided together with comparative line scans obtained with contact mode imaging. An imaging bandwidth of 30 kHz inmore » air with the current setup was demonstrated.« less
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High-temperature fiber-optic lever microphone
NASA Technical Reports Server (NTRS)
Zuckerwar, Allan J.; Cuomo, Frank W.; Nguyen, Trung D.; Rizzi, Stephen A.; Clevenson, Sherman A.
1995-01-01
The design and construction of a fiber-optic lever microphone, capable of operating continuously at temperatures up to 538 C (1000 F) are described. The design is based on the theoretical sensitivities of each of the microphone system components, namely, a cartridge containing a stretched membrane, an optical fiber probe, and an optoelectronic amplifier. Laboratory calibrations include the pistonphone sensitivity and harmonic distortion at ambient temperature, and frequency response, background noise, and optical power transmission at both ambient and elevated temperatures. A field test in the Thermal Acoustic Fatigue Apparatus at Langley Research Center, in which the microphone was subjected to overall sound-pressure levels in the range of 130-160 dB and at temperatures from ambient to 538 C, revealed good agreement with a standard probe microphone.
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Simple force feedback for small virtual environments
NASA Astrophysics Data System (ADS)
Schiefele, Jens; Albert, Oliver; van Lier, Volker; Huschka, Carsten
1998-08-01
In today's civil flight training simulators only the cockpit and all its interaction devices exist as physical mockups. All other elements such as flight behavior, motion, sound, and the visual system are virtual. As an extension to this approach `Virtual Flight Simulation' tries to subsidize the cockpit mockup by a 3D computer generated image. The complete cockpit including the exterior view is displayed on a Head Mounted Display (HMD), a BOOM, or a Cave Animated Virtual Environment. In most applications a dataglove or virtual pointers are used as input devices. A basic problem of such a Virtual Cockpit simulation is missing force feedback. A pilot cannot touch and feel buttons, knobs, dials, etc. he tries to manipulate. As a result, it is very difficult to generate realistic inputs into VC systems. `Seating Bucks' are used in automotive industry to overcome the problem of missing force feedback. Only a seat, steering wheel, pedal, stick shift, and radio panel are physically available. All other geometry is virtual and therefore untouchable but visible in the output device. In extension to this concept a `Seating Buck' for commercial transport aircraft cockpits was developed. Pilot seat, side stick, pedals, thrust-levers, and flaps lever are physically available. All other panels are simulated by simple flat plastic panels. They are located at the same location as their real counterparts only lacking the real input devices. A pilot sees the entire photorealistic cockpit in a HMD as 3D geometry but can only touch the physical parts and plastic panels. In order to determine task performance with the developed Seating Buck, a test series was conducted. Users press buttons, adapt dials, and turn knobs. In a first test, a complete virtual environment was used. The second setting had a plastic panel replacing all input devices. Finally, as cross reference the participants had to repeat the test with a complete physical mockup of the input devices. All panels and physical devices can be easily relocated to simulate a different type of cockpit. Maximal 30 minutes are needed for a complete adaptation. So far, an Airbus A340 and a generic cockpit are supported.
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Early Visual Cortex Dynamics during Top-Down Modulated Shifts of Feature-Selective Attention.
Müller, Matthias M; Trautmann, Mireille; Keitel, Christian
2016-04-01
Shifting attention from one color to another color or from color to another feature dimension such as shape or orientation is imperative when searching for a certain object in a cluttered scene. Most attention models that emphasize feature-based selection implicitly assume that all shifts in feature-selective attention underlie identical temporal dynamics. Here, we recorded time courses of behavioral data and steady-state visual evoked potentials (SSVEPs), an objective electrophysiological measure of neural dynamics in early visual cortex to investigate temporal dynamics when participants shifted attention from color or orientation toward color or orientation, respectively. SSVEPs were elicited by four random dot kinematograms that flickered at different frequencies. Each random dot kinematogram was composed of dashes that uniquely combined two features from the dimensions color (red or blue) and orientation (slash or backslash). Participants were cued to attend to one feature (such as color or orientation) and respond to coherent motion targets of the to-be-attended feature. We found that shifts toward color occurred earlier after the shifting cue compared with shifts toward orientation, regardless of the original feature (i.e., color or orientation). This was paralleled in SSVEP amplitude modulations as well as in the time course of behavioral data. Overall, our results suggest different neural dynamics during shifts of attention from color and orientation and the respective shifting destinations, namely, either toward color or toward orientation.
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Davy, Jonathan; Göbel, Matthias
2013-01-01
This study compared the effects of a 1 h self-selected recovery period to those of a standard night shift arrangement (with a total break time of 1-h) over a simulated three-day night shift schedule in a laboratory setting. Results showed that the inclusion of the flexible nap scheme resulted in higher performance output, improvements in physiological strain responses and reduced sleepiness during each night shift and generally over the three-night cycle. Certain variables also revealed the impact of napping compared with the standard rest break condition on the circadian rhythm. The sleep diary records show that the inclusion of the current intervention did not significantly reduce daytime recovery sleep. The results suggest that the potential benefits of flexible napping may outweigh the logistical effort it requires in a workplace environment. Consensus on appropriate napping strategies for shift work remains a challenge. This simulated night shift laboratory study sought to determine the effects of a 1-h self-selected nap opportunity relative to a normal shift set-up. The nap improved performance and decreased sleepiness, without affecting daytime sleep.
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R(+)-Baclofen, but Not S(-)-Baclofen, Alters Alcohol Self-Administration in Alcohol-Preferring Rats.
Lorrai, Irene; Maccioni, Paola; Gessa, Gian Luigi; Colombo, Giancarlo
2016-01-01
Racemic baclofen [(±)-baclofen] has repeatedly been reported to suppress several -alcohol-motivated behaviors, including alcohol drinking and alcohol -self-administration, in rats and mice. Recent data suggested that baclofen may have bidirectional, stereospecific effects, with the more active enantiomer, R(+)-baclofen, suppressing alcohol intake and the less active enantiomer, S(-)-baclofen, stimulating alcohol intake in mice. The present study was designed to investigate whether this enantioselectivity of baclofen effects may also extend to the reinforcing properties of alcohol in rats. To this end, selectively bred Sardinian alcohol-preferring (sP) rats were initially trained to lever respond on a fixed ratio 4 (FR4) schedule of reinforcement for alcohol (15%, v/v) in daily 30-min sessions. Once responding had stabilized, rats were tested with vehicle, (±)-baclofen (3 mg/kg), R(+)-baclofen (0.75, 1.5, and 3 mg/kg), and S(-)-baclofen (6, 12, and 24 mg/kg) under the FR4 schedule of reinforcement. Treatment with 3 mg/kg (±)-baclofen reduced the number of lever responses for alcohol and estimated amount of self-administered alcohol by approximately 60% in comparison to vehicle treatment. R(+)-baclofen was approximately twice as active as (±)-baclofen: treatment with 1.5 mg/kg R(+)-baclofen decreased both variables to an extent similar to that of the decreasing effect of 3 mg/kg (±)-baclofen. Conversely, treatment with all doses of S(-)-baclofen failed to affect alcohol self administration. These results (a) confirm that non-sedative doses of (±)-baclofen effectively suppressed the reinforcing properties of alcohol in sP rats and (b) apparently do not extend to operant alcohol self-administration in sP rats the capability of S(-)-baclofen to stimulate alcohol drinking in mice.
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Silenieks, Leo B; Koch, Egon; Higgins, Guy A
2013-01-15
Recently, an essential oil of selected quality produced from the flowering tops of Lavandula angustifolia Mill. by steam distillation (Silexan) has been approved in Germany for the treatment of restlessness in case of anxious mood. Based on the observed clinical effects, it has been speculated that lavender oil may exert benzodiazepine-like action including the known dependence and abuse potential of this class of drugs. Although no evidence for such an activity was generated during the long-standing medicinal use of lavender oil, further preclinical investigations were now conducted to evaluate this potential side effect in more detail. Twelve adult, male, Sprague-Dawley rats were trained to discriminate the benzodiazepine drug diazepam (2 mg/kg i.p.) from saline using a two-lever operant procedure. After approximately 40 training sessions the majority of rats learned the discrimination and pre-treatment with ascending doses of diazepam (0.3-2 mg/kg i.p.) produced a dose related generalization to the diazepam cue. In these same animals Silexan was administered to see if animals recognized the drug as "diazepam-like" i.e. generalized to diazepam or "saline-like". Silexan tested at doses 3-30 mg/kg i.p. produced almost exclusively (>90%) saline-like responding. Also there was no effect of Silexan on response rate, i.e. rate of lever pressing, at any dose suggesting that the test article is well tolerated and does not exert a sedating effect. In sum, Silexan has no diazepam-like interoceptive property in adult, male rats. This suggests that Silexan does not share the potential of benzodiazepines to induce the development of tolerance, dependence and addiction. Copyright © 2012 Elsevier GmbH. All rights reserved.
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Winstanley, Catharine A; Cocker, Paul J; Rogers, Robert D
2011-01-01
Cognitive accounts of gambling suggest that the experience of almost winning—so-called ‘near-misses'—encourage continued play and accelerate the development of pathological gambling (PG) in vulnerable individuals. One explanation for this effect is that near-misses signal imminent winning outcomes and heighten reward expectancy, galvanizing further play. Determining the neurochemical processes underlying the drive to gamble could facilitate the development of more effective treatments for PG. With this aim in mind, we evaluated rats' performance on a novel model of slot machine play, a form of gambling in which near-miss events are particularly salient. Subjects responded to a series of three flashing lights, loosely analogous to the wheels of a slot machine, causing the lights to set to ‘on' or ‘off'. A winning outcome was signaled if all three lights were illuminated. At the end of each trial, rats chose between responding on the ‘collect' lever, resulting in reward on win trials, but a time penalty on loss trials, or starting a new trial. Rats showed a marked preference for the collect lever when both two and three lights were illuminated, indicating heightened reward expectancy following near-misses similar to wins. Erroneous collect responses were increased by amphetamine and the D2 receptor agonist quinpirole, but not by the D1 receptor agonist SKF 81297 or receptor subtype selective antagonists. These data suggest that dopamine modulates reward expectancy following the experience of almost winning during slot machine play, via activity at D2 receptors, and this may result in an enhancement of the near-miss effect and facilitate further gambling. PMID:21209612
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Winstanley, Catharine A; Cocker, Paul J; Rogers, Robert D
2011-04-01
Cognitive accounts of gambling suggest that the experience of almost winning-so-called 'near-misses'-encourage continued play and accelerate the development of pathological gambling (PG) in vulnerable individuals. One explanation for this effect is that near-misses signal imminent winning outcomes and heighten reward expectancy, galvanizing further play. Determining the neurochemical processes underlying the drive to gamble could facilitate the development of more effective treatments for PG. With this aim in mind, we evaluated rats' performance on a novel model of slot machine play, a form of gambling in which near-miss events are particularly salient. Subjects responded to a series of three flashing lights, loosely analogous to the wheels of a slot machine, causing the lights to set to 'on' or 'off'. A winning outcome was signaled if all three lights were illuminated. At the end of each trial, rats chose between responding on the 'collect' lever, resulting in reward on win trials, but a time penalty on loss trials, or starting a new trial. Rats showed a marked preference for the collect lever when both two and three lights were illuminated, indicating heightened reward expectancy following near-misses similar to wins. Erroneous collect responses were increased by amphetamine and the D(2) receptor agonist quinpirole, but not by the D(1) receptor agonist SKF 81297 or receptor subtype selective antagonists. These data suggest that dopamine modulates reward expectancy following the experience of almost winning during slot machine play, via activity at D(2) receptors, and this may result in an enhancement of the near-miss effect and facilitate further gambling.
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A novel approach to determine primary stability of acetabular press-fit cups.
Weißmann, Volker; Boss, Christian; Bader, Rainer; Hansmann, Harald
2018-04-01
Today hip cups are used in a large variety of design variants and in increasing numbers of units. Their development is steadily progressing. In addition to conventional manufacturing methods for hip cups, additive methods, in particular, play an increasingly important role as development progresses. The present paper describes a modified cup model developed based on a commercially available press-fit cup (Allofit 54/JJ). The press-fit cup was designed in two variants and manufactured using selective laser melting (SLM). Variant 1 (Ti) was modeled on the Allofit cup using an adapted process technology. Variant 2 (Ti-S) was provided with a porous load bearing structure on its surface. In addition to the typical (complete) geometry, both variants were also manufactured and tested in a reduced shape where only the press-fit area was formed. To assess the primary stability of the press-fit cups in the artificial bone cavity, pull-out and lever-out tests were carried out. Exact fit conditions and two-millimeter press-fit were investigated. The closed-cell PU foam used as an artificial bone cavity was mechanically characterized to exclude any influence on the results of the investigation. The pull-out forces of the Ti-variant (complete-526 N, reduced-468 N) and the Ti-S variant (complete-548 N, reduced-526 N) as well as the lever-out moments of the Ti-variant (complete-10 Nm, reduced-9.8 Nm) and the Ti-S variant (complete-9 Nm, reduced-7.9 N) show no significant differences in the results between complete and reduced cups. The results show that the use of reduced cups in a press-fit design is possible within the scope of development work. Copyright © 2018 Elsevier Ltd. All rights reserved.
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Effects of delay to reinforcement on the choice between cocaine and food in rhesus monkeys.
Woolverton, William L; Anderson, Karen G
2006-05-01
Although a delay between behavior and reinforcer has been shown to weaken behavior, little is known about the effects of delay on drug choice. The present study examined effects of delay between lever press and reinforcer presentation on the choice between a drug and non-drug reinforcer and between different drug doses. Monkeys (n=4) were allowed to choose 32 times/day between cocaine and four food pellets. The delay between lever press and a preferred dose of cocaine (0.05 mg/kg/injection) was increased systematically from 0 to 240 s, while the delay to food remained at 0 s. A second group of monkeys (n=4) was allowed to choose between 0.05 mg/kg/injection and a lower dose of cocaine (0.025 mg/kg/injection). Next, a delay that resulted in less than 20% choice of 0.05 mg/kg/injection cocaine was selected and delay to the alternative was varied. Results were similar across groups. The choice of 0.05 mg/kg/injection approximated 100% at 0 delay and decreased to near 0 as delay increased. As the delay to alternative was subsequently increased from 0 to 240 s, choice of 0.05 mg/kg/injection increased, though full cocaine choice was not generally restored. The delay estimated to maintain 50% choice (indifference point) was lower for the cocaine-food choice (mean=64 s) than for the cocaine-cocaine choice (mean=207 s). This experiment demonstrates that the choice between cocaine and a non-drug or drug alternative can be modified by increasing the interval between behavior and drug injection. Overall, the results are consistent with a temporal discounting model of drug choice.
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Gresch, Paul J; Barrett, Robert J; Sanders-Bush, Elaine; Smith, Randy L
2007-02-01
d-Lysergic acid diethylamide (LSD), an indoleamine hallucinogen, produces profound alterations in mood, thought, and perception in humans. The brain site(s) that mediates the effects of LSD is currently unknown. In this study, we combine the drug discrimination paradigm with intracerebral microinjections to investigate the anatomical localization of the discriminative stimulus of LSD in rats. Based on our previous findings, we targeted the anterior cingulate cortex (ACC) to test its involvement in mediating the discriminative stimulus properties of LSD. Rats were trained to discriminate systemically administered LSD (0.085 mg/kg s.c.) from saline. Following acquisition of the discrimination, bilateral cannulae were implanted into the ACC (AP, +1.2 mm; ML, +/-1.0 mm; DV, -2.0 mm relative to bregma). Rats were tested for their ability to discriminate varying doses of locally infused LSD (0.1875, 0.375, and 0.75 microg/side) or artificial cerebrospinal fluid (n = 3-7). LSD locally infused into ACC dose-dependently substituted for systemically administered LSD, with 0.75 microg/side LSD substituting completely (89% correct). Systemic administration of the selective 5-hydroxytryptamine (serotonin) (5-HT)(2A) receptor antagonist R-(+)-alpha-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenylethyl)]-4-piperidine-methanol (M100907; 0.4 mg/kg) blocked the discriminative cue of LSD (0.375 microg/side) infused into ACC (from 68 to 16% drug lever responding). Furthermore, M100907 (0.5 microg/microl/side) locally infused into ACC completely blocked the stimulus effects of systemic LSD (0.04 mg/kg; from 80 to 12% on the LSD lever). Taken together, these data indicate that 5-HT(2A) receptors in the ACC are a primary target mediating the discriminative stimulus properties of LSD.
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Characterization of the discriminative stimulus produced by the dopamine antagonist tiapride.
Cohen, C; Sanger, D J; Perrault, G
1997-11-01
The ability of tiapride, a selective D2/D3 dopamine receptor antagonist, to exert discriminative stimulus control of responding was investigated by training rats to discriminate this drug (30 mg/kg) from saline in a two-lever, food-reinforcement procedure. Acquisition of tiapride discrimination required a relatively lengthy training period (mean of 76 sessions) but stable performance was maintained throughout the 18- month study. The dose of tiapride eliciting 50% tiapride-lever choice (ED50) was 2.2 mg/kg. After determination of the dose-effect curve with tiapride, substitution tests with several dopamine antagonists and other reference compounds were performed. All dopamine antagonists, including amisulpride (ED50 4 mg/kg), sulpiride (18 mg/kg), sultopride (1.5 mg/kg), clebopride (0.13 mg/kg), raclopride (0.16 mg/kg), metoclopramide (1.4 mg/kg), remoxipride (4.8 mg/kg), pimozide (2.7 mg/kg), thioridazine (3.4 mg/kg), olanzapine (0.97 mg/kg), chlorpromazine (1.9 mg/kg), risperidone (0.22 mg/kg) and haloperidol (0.14 mg/kg), except clozapine (>10 mg/kg), produced dose-dependent substitution for tiapride. Tiapride-like stimulus effects were observed at doses that decreased response rates. However, ED50 values for substitution by tiapride, amisulpride, sulpiride, sultopride, pimozide, clebopride and thioridazine were lower than ED50 values for decreasing responding. Additional studies were conducted to evaluate the ability of direct and indirect dopamine agonists to attenuate the tiapride discriminative stimulus. Pretreatment with d-amphetamine and nomifensine antagonized the discriminative stimulus effects of tiapride. Quinpirole, 7-OH-DPAT, bromocriptine and apomorphine partially blocked the stimulus effects of tiapride whereas SKF 38393 did not affect the discrimination. These results from substitution and antagonism tests indicated that the discriminative effects of tiapride are mediated by activity at D2/D3 dopamine receptors.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Nadeau, Jeremy S.; Wright, Bob W.; Synovec, Robert E.
2010-04-15
A critical comparison of methods for correcting severely retention time shifted gas chromatography-mass spectrometry (GC-MS) data is presented. The method reported herein is an adaptation to the Piecewise Alignment Algorithm to quickly align severely shifted one-dimensional (1D) total ion current (TIC) data, then applying these shifts to broadly align all mass channels throughout the separation, referred to as a TIC shift function (SF). The maximum shift varied from (-) 5 s in the beginning of the chromatographic separation to (+) 20 s toward the end of the separation, equivalent to a maximum shift of over 5 peak widths. Implementing themore » TIC shift function (TIC SF) prior to Fisher Ratio (F-Ratio) feature selection and then principal component analysis (PCA) was found to be a viable approach to classify complex chromatograms, that in this study were obtained from GC-MS separations of three gasoline samples serving as complex test mixtures, referred to as types C, M and S. The reported alignment algorithm via the TIC SF approach corrects for large dynamic shifting in the data as well as subtle peak-to-peak shifts. The benefits of the overall TIC SF alignment and feature selection approach were quantified using the degree-of-class separation (DCS) metric of the PCA scores plots using the type C and M samples, since they were the most similar, and thus the most challenging samples to properly classify. The DCS values showed an increase from an initial value of essentially zero for the unaligned GC-TIC data to a value of 7.9 following alignment; however, the DCS was unchanged by feature selection using F-Ratios for the GC-TIC data. The full mass spectral data provided an increase to a final DCS of 13.7 after alignment and two-dimensional (2D) F-Ratio feature selection.« less
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The effects of response cost and species-typical behaviors on a daily time-place learning task.
Deibel, Scott H; Thorpe, Christina M
2013-03-01
Two theories that have been hypothesized to mediate acquisition in daily time-place learning (TPL) tasks were investigated in a free operant daily TPL task: the response cost hypothesis and the species-typical behavior hypothesis. One lever at the end of one of the choice arms of a T-maze provided food in the morning, and 6 h later, a lever in the other choice arm provided food. Four groups were used to assess the effect of two possible sources of response cost: physical effort of the task and costs associated with foraging ecology. One group was used to assess the effect of explicitly allowing for species-typical behaviors. If only first arm choice data were considered, there was little evidence of learning. However, both first press and percentage of presses on the correct lever prior to the first reinforcement revealed evidence of TPL in most rats tested. Unexpectedly, the high response cost groups for both of the proposed sources did not perform better than the low response cost groups. The groups that allowed animals to display species-typical behaviors performed the worst. Skip session probe trials confirmed that the majority of the rats that acquired the task were using a circadian timing strategy. The results from the present study suggest that learning in free operant daily TPL tasks might not be dependent on response cost.
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Controllable molecular motors engineered from myosin and RNA
NASA Astrophysics Data System (ADS)
Omabegho, Tosan; Gurel, Pinar S.; Cheng, Clarence Y.; Kim, Laura Y.; Ruijgrok, Paul V.; Das, Rhiju; Alushin, Gregory M.; Bryant, Zev
2018-01-01
Engineering biomolecular motors can provide direct tests of structure-function relationships and customized components for controlling molecular transport in artificial systems1 or in living cells2. Previously, synthetic nucleic acid motors3-5 and modified natural protein motors6-10 have been developed in separate complementary strategies to achieve tunable and controllable motor function. Integrating protein and nucleic-acid components to form engineered nucleoprotein motors may enable additional sophisticated functionalities. However, this potential has only begun to be explored in pioneering work harnessing DNA scaffolds to dictate the spacing, number and composition of tethered protein motors11-15. Here, we describe myosin motors that incorporate RNA lever arms, forming hybrid assemblies in which conformational changes in the protein motor domain are amplified and redirected by nucleic acid structures. The RNA lever arm geometry determines the speed and direction of motor transport and can be dynamically controlled using programmed transitions in the lever arm structure7,9. We have characterized the hybrid motors using in vitro motility assays, single-molecule tracking, cryo-electron microscopy and structural probing16. Our designs include nucleoprotein motors that reversibly change direction in response to oligonucleotides that drive strand-displacement17 reactions. In multimeric assemblies, the controllable motors walk processively along actin filaments at speeds of 10-20 nm s-1. Finally, to illustrate the potential for multiplexed addressable control, we demonstrate sequence-specific responses of RNA variants to oligonucleotide signals.
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NASA Astrophysics Data System (ADS)
Daakir, M.; Pierrot-Deseilligny, M.; Bosser, P.; Pichard, F.; Thom, C.; Rabot, Y.
2016-03-01
Nowadays, Unmanned Aerial Vehicle (UAV) on-board photogrammetry knows a significant growth due to the democratization of using drones in the civilian sector. Also, due to changes in regulations laws governing the rules of inclusion of a UAV in the airspace which become suitable for the development of professional activities. Fields of application of photogrammetry are diverse, for instance: architecture, geology, archaeology, mapping, industrial metrology, etc. Our research concerns the latter area. Vinci-Construction- Terrassement is a private company specialized in public earthworks that uses UAVs for metrology applications. This article deals with maximum accuracy one can achieve with a coupled camera and GPS receiver system for direct-georeferencing of Digital Surface Models (DSMs) without relying on Ground Control Points (GCPs) measurements. This article focuses specially on the lever-arm calibration part. This proposed calibration method is based on two steps: a first step involves the proper calibration for each sensor, i.e. to determine the position of the optical center of the camera and the GPS antenna phase center in a local coordinate system relative to the sensor. A second step concerns a 3d modeling of the UAV with embedded sensors through a photogrammetric acquisition. Processing this acquisition allows to determine the value of the lever-arm offset without using GCPs.
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Marquillier, Thomas; Trentesaux, Thomas; Gagnayre, Rémi
2017-01-01
Over recent years, therapeutic patient education has become part of dental medicine. Management of early childhood caries, known to be a very common chronic disease, has evolved to include an educational dimension. The objective of this study was to identify the levers and barriers to the development of formalized therapeutic education programmes and alternatives. A comprehensive exploratory qualitative study was conducted between November 2015 and June 2016 on a targeted sample of 15 people aware of the problem of TPE in dentistry. The study showed that TPE training in dentistry is underdeveloped, despite its numerous benefits: change of the healthcare professional's approach, implementation of structured educational programmes, development of research, etc. There are many obstacles to the development of TPE programmes: insufficient resources, rigid legislation or lack of knowledge of TPE practices. The dental profession is an obstacle itself because of its lack of understanding and variable degrees of integration the medical community. There are multiple levers, but the main ones are changing attitudes of the profession and the provision of resources to develop TPE. Although alternatives to TPE programmes exist (accompanying measures, short educational strategies, connected health), they cannot replace TPE. More educational strategies must be developed in the field of dentistry. However, the framework of TPE must be adapted to the profession to ensure good uptake.
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Bridger, R S; Cabion, N; Goedecke, J; Rickard, S; Schabort, E; Westgarth-Taylor, C; Lambert, M I
1997-11-01
Previous studies have suggested that the two-handled (levered) shovel is advantageous over the conventional spade from a biomechanical point of view. The aim of this experiment was to determine whether less energy was consumed while shovelling a load of sand with this shovel compared to a conventional tool. Accordingly, an experiment was designed in which subjects (n = 10) shovelled 1815 kg sand under laboratory conditions using either a conventional or a levered shovel. Heart rate and oxygen consumption were measured continuously during the trial and subjective data on perceived exertion, general fatigue and body discomfort were recorded after the trial. Although total energy expenditure was similar under both conditions (120 +/- 20 and 125 +/- 25 kcal; conventional versus two-handled spade), average heart rate was 4% higher when the two-handled shovel was used (p < 0.05). In addition, the mass of sand per scoop was 4% less with the two-handled shovel (p < 0.05). In conclusion, subjects used similar energy expenditure to shovel 1815 kg sand with the conventional shovel and the two-handled tool despite lower mass of sand per scoop with the latter. This can be explained by the fact that the increased mass of the additional handle compensated for the lower mass of sand per scoop. The higher average heart rate while shovelling with the two-handled shovel can be explained by the more erect posture.
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Ghrelin enhances cue-induced bar pressing for high fat food.
St-Onge, Veronique; Watts, Alexander; Abizaid, Alfonso
2016-02-01
Ghrelin is an orexigenic hormone produced by the stomach that acts on growth hormone secretagogue receptors (GHSRs) both peripherally and centrally. The presence of GHSRs in the ventral tegmental area (VTA) suggests that ghrelin signaling at this level may increase the incentive value of palatable foods as well as other natural and artificial rewards. The present investigation sought to determine if ghrelin plays a role in relapse to such foods following a period of abstinence. To achieve this, thirty-six male Long Evans rats were trained to press a lever to obtain a high fat chocolate food reward on a fixed ratio schedule of 1. Following an extinction period during which lever presses were not reinforced, rats were implanted with a cannula connected to a minipump that continuously delivered ghrelin, a GHSR antagonist ([d-Lys-3]-GHRP-6), or saline in the VTA for 14days. One week later, food reward-associated cues, food reward priming, and an overnight fast were used to induce reinstatement of the lever pressing response. Our results indicate that intra-VTA ghrelin enhances cue-induced reinstatement of responses for palatable food pellets. To the extent that the reinstatement paradigm is considered a valid model of relapse in humans, this suggests that ghrelin signaling facilitates relapse to preferred foods in response to food cues through GHSR signaling in the VTA. Copyright © 2015 Elsevier Inc. All rights reserved.
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Shiflett, Michael W; Riccie, Meaghan; DiMatteo, RoseMarie
2013-11-01
Psychostimulant sensitization heightens behavioral and motivational responses to reward-associated stimuli; however, its effects on stimuli associated with reward absence are less understood. We examined whether amphetamine sensitization alters performance during Pavlovian-instrumental transfer (PIT) to conditioned excitors and inhibitors. We further sought to characterize the effects of amphetamine sensitization on learning versus performance by exposing rats to amphetamine prior to Pavlovian training or between training and test. Adult male Long-Evans rats were given conditioned inhibition (A+/AX-) and Pavlovian (B+) training, followed by variable-interval instrumental conditioning. Rats were sensitized to D-amphetamine (2 mg/kg daily injections for 7 days) or served as non-exposed controls. Rats were given a PIT test, in which they were presented with stimulus B alone or in compound with the conditioned inhibitor (BX). During the PIT test, control rats significantly reduced instrumental responding on BX trials (to approximately 50 % of responding to B). Amphetamine sensitization prior to Pavlovian conditioning increased lever pressing on BX trials and reduced lever pressing on B trials compared to controls. Amphetamine sensitization between training and test increased lever pressing on B and BX trials compared to controls. No effects of sensitization were observed on conditioned food cup approach. Amphetamine sensitization increases instrumental responding during PIT to a conditioned inhibitor by enhancing the excitation of conditioned stimuli and reducing the inhibition of conditioned inhibitors.
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NASA Astrophysics Data System (ADS)
Moksnes, Nandi; Taliotis, Constantinos; Broad, Oliver; de Moura, Gustavo; Howells, Mark
2017-04-01
Developing a set of scenarios to assess a proposed policy or future development pathways requires a certain level of information, as well as establishing the socio-economic context. As the future is difficult to predict, great care in defining the selected scenarios is needed. Even so it can be difficult to assess if the selected scenario is covering the possible solution space. Instead, this paper's methodology develops a large set of scenarios (324) in OSeMOSYS using the SAMBA 2.0 (South America Model Base) model to assess long-term electricity supply scenarios and applies a scenario-discovery statistical data mining algorithm, Patient Rule Induction Method (PRIM). By creating a multidimensional space, regions related to high and low cost can be identified as well as their key driver. The six key drivers are defined a priori in three (high, medium, low) or two levers (high, low): 1) Demand projected from GDP, population, urbanization and transport, 2) Fossil fuel price, 3) Climate change impact on hydropower, 4) Renewable technology learning rate, 5) Discount rate, 6) CO2 emission targets.
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Dunovan, Kyle; Verstynen, Timothy
2016-01-01
The flexibility of behavioral control is a testament to the brain's capacity for dynamically resolving uncertainty during goal-directed actions. This ability to select actions and learn from immediate feedback is driven by the dynamics of basal ganglia (BG) pathways. A growing body of empirical evidence conflicts with the traditional view that these pathways act as independent levers for facilitating (i.e., direct pathway) or suppressing (i.e., indirect pathway) motor output, suggesting instead that they engage in a dynamic competition during action decisions that computationally captures action uncertainty. Here we discuss the utility of encoding action uncertainty as a dynamic competition between opposing control pathways and provide evidence that this simple mechanism may have powerful implications for bridging neurocomputational theories of decision making and reinforcement learning. PMID:27047328
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Dunovan, Kyle; Verstynen, Timothy
2016-01-01
The flexibility of behavioral control is a testament to the brain's capacity for dynamically resolving uncertainty during goal-directed actions. This ability to select actions and learn from immediate feedback is driven by the dynamics of basal ganglia (BG) pathways. A growing body of empirical evidence conflicts with the traditional view that these pathways act as independent levers for facilitating (i.e., direct pathway) or suppressing (i.e., indirect pathway) motor output, suggesting instead that they engage in a dynamic competition during action decisions that computationally captures action uncertainty. Here we discuss the utility of encoding action uncertainty as a dynamic competition between opposing control pathways and provide evidence that this simple mechanism may have powerful implications for bridging neurocomputational theories of decision making and reinforcement learning.
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[Influence of stress on learning and memory].
Ukai, M
2000-08-01
This paper describes the influence of stress on learning and memory. The mice receiving inescapable electroshock fail to perform the active conditioned avoidance response of lever-pressing. This is called learned helplessness, which is ameliorated by treatment with antidepressants including one of the selective serotonin reuptake inhibitors (SSRIs). It is of particular interest that posttraumatic stress disease (PTSD) accompanied by memory impairment could be improved by treatment with SSRIs. The different kinds of stress including ischemia, footshock, psychological stress, and forced swimming influence learning and memory as indexed by spontaneous alternation performance as well as passive avoidance learning. In addition, a variety of stresses influence the activity of hormones and neurotransmitters like monoamines, neuropeptides, and excitatory amino acids resulting in changes in learning and memory. Finally, the accumulation of data is necessary to clarify the exact mechanism of stress on learning and memory.
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Age differences in strategy shift: retrieval avoidance or general shift reluctance?
Frank, David J; Touron, Dayna R; Hertzog, Christopher
2013-09-01
Previous studies of metacognitive age differences in skill acquisition strategies have relied exclusively on tasks with a processing shift from an algorithm to retrieval strategy. Older adults' demonstrated reluctance to shift strategies in such tasks could reflect either a specific aversion to a memory retrieval strategy or a general, inertial resistance to strategy change. Haider and Frensch's (1999) alphabet verification task (AVT) affords a non-retrieval-based strategy shift. Participants verify the continuation of alphabet strings such as D E F G [4] L, with the bracketed digit indicating a number of letters to be skipped. When all deviations are restricted to the letter-digit-letter portion, participants can speed their responses by selectively attending to only that part of the stimulus. We adapted the AVT to include conditions that promoted shift to a retrieval strategy, a selective attention strategy, or both strategies. Item-level strategy reports were validated by eye movement data. Older adults shifted more slowly to the retrieval strategy but more quickly to the selective attention strategy than young adults, indicating a retrieval-strategy avoidance. Strategy confidence and perceived strategy difficulty correlated with shift to the two strategies in both age groups. Perceived speed of responses with each strategy specifically correlated with older adults' strategy choices, suggesting that some older adults avoid retrieval because they do not appreciate its efficiency benefits.
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Age Differences in Strategy Shift: Retrieval Avoidance or General Shift Reluctance?
Frank, David J.; Touron, Dayna R.; Hertzog, Christopher
2013-01-01
Previous studies of metacognitive age differences in skill acquisition strategies have relied exclusively on tasks with a processing shift from an algorithm to retrieval strategy. Older adults’ demonstrated reluctance to shift strategies in such tasks could reflect either a specific aversion to a memory retrieval strategy or a general, inertial resistance to strategy change. Haider and Frensch’s (1999) alphabet verification task (AVT) affords a non-retrieval-based strategy shift. Participants verify the continuation of alphabet strings such as D E F G [4] L, with the bracketed digit indicating a number of letters to be skipped. When all deviations are restricted to the letter-digit-letter portion, participants can speed their responses by selectively attend only to that part of the stimulus. We adapted the AVT to include conditions which promoted shift to a retrieval strategy, a selective attention strategy, or both strategies. Item-level strategy reports were validated by eye movement data. Older adults shifted more slowly to the retrieval strategy but more quickly to the selective attention strategy than young adults, indicating a retrieval-strategy avoidance. Strategy confidence and perceived strategy difficulty correlated with shift to the two strategies in both age groups. Perceived speed of responses with each strategy specifically correlated with older adults’ strategy choices, suggesting that some older adults avoid retrieval because they do not appreciate its efficiency benefits. PMID:23088195
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A progressive model for teaching children with autism to follow gaze shift.
Gunby, Kristin V; Rapp, John T; Bottoni, Melissa M
2018-06-06
Gunby, Rapp, Bottoni, Marchese and Wu () taught three children with autism spectrum disorder to follow an instructor's gaze shift to select a specific item; however, Gunby et al. used different types of prompts with each participant. To address this limitation, we used a progressive training model for increasing gaze shift for three children with autism spectrum disorder. Results show that each participant learned to follow an adult's shift in gaze to make a correct selection. In addition, two participants displayed the skill in response to a parent's gaze shift and with only social consequences; however, the third participant required verbal instruction and tangible reinforcement to demonstrate the skill outside of training sessions. © 2018 Society for the Experimental Analysis of Behavior.
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Tahara, Tatsuki; Otani, Reo; Omae, Kaito; Gotohda, Takuya; Arai, Yasuhiko; Takaki, Yasuhiro
2017-05-15
We propose multiwavelength in-line digital holography with wavelength-multiplexed phase-shifted holograms and arbitrary symmetric phase shifts. We use phase-shifting interferometry selectively extracting wavelength information to reconstruct multiwavelength object waves separately from wavelength-multiplexed monochromatic images. The proposed technique obtains systems of equations for real and imaginary parts of multiwavelength object waves from the holograms by introducing arbitrary symmetric phase shifts. Then, the technique derives each complex amplitude distribution of each object wave selectively and analytically by solving the two systems of equations. We formulate the algorithm in the case of an arbitrary number of wavelengths and confirm its validity numerically and experimentally in the cases where the number of wavelengths is two and three.
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Khatibi, Ali; Dehghani, Mohsen; Sharpe, Louise; Asmundson, Gordon J G; Pouretemad, Hamidreza
2009-03-01
Evidence that patients with chronic pain selectively attend to pain-related stimuli presented in modified Stroop and dot-probe paradigms is mixed. The pain-related stimuli used in these studies have been primarily verbal in nature (i.e., words depicting themes of pain). The purpose of the present study was to determine whether patients with chronic pain, relative to healthy controls, show selective attention for pictures depicting painful faces. To do so, 170 patients with chronic pain and 40 age- and education-matched healthy control participants were tested using a dot-probe task in which painful, happy, and neutral facial expressions were presented. Selective attention was denoted using the mean reaction time and the bias index. Results indicated that, while both groups shifted attention away from happy faces (and towards neutral faces), only the control group shifted attention away from painful faces. Additional analyses were conducted on chronic pain participants after dividing them into groups on the basis of fear of pain/(re)injury. The results of these analyses revealed that while chronic pain patients with high and low levels of fear both shifted attention away from happy faces, those with low fear shifted attention away from painful faces, whereas those with high fear shifted attention towards painful faces. These results suggest that patients with chronic pain selectively attend to facial expressions of pain and, importantly, that the tendency to shift attention towards such stimuli is positively influenced by high fear of pain/(re)injury. Implications of the findings and future research directions are discussed.
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... teeth and on the joint. In terms of physics, the jaw is the lever and the TMJ ... management of TMJ pain. Updated 12-10 Patient Health Home Copyright © 2018 American Academy of Otolaryngology–Head ...
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Blackouts Before the blackout... - If you have an electric garage door opener, locate the manual release lever and learn how to operate it. - Keep your car’s gas tank at least half full; gas stations ...
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Dose and elasticity of demand for self-administered cocaine in rats.
Kearns, David N; Silberberg, Alan
2016-04-01
The present experiment tested whether the elasticity of demand for self-administered cocaine in rats is dose-dependent. Subjects lever pressed for three different doses of intravenous cocaine - 0.11, 0.33, and 1.0 mg/kg/infusion - on a demand procedure where the number of lever presses required per infusion increased within a session. The main finding was that demand for the 0.11 mg/kg dose was more elastic than it was for the two larger doses. There was no difference in demand elasticity between the 0.33 and 1.0 mg/kg doses. These results parallel findings previously reported in monkeys. The present study also demonstrated that a within-session procedure can be used to generate reliable demand curves.
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Automation of Underground Cable Laying Equipment Using PLC and Hmi
NASA Astrophysics Data System (ADS)
Mal Kothari, Kesar; Samba, Vishweshwar; Tania, Kinza; Udayakumar, R., Dr; Karthikeyan, Ram, Dr
2018-04-01
Underground cable laying is an alternative for overhead cable laying of telecommunication and power transmission lines. It is becoming very popular in recent times because of some of its advantages over overhead cable laying. This type of cable laying is mostly practiced in developed countries because it is more expensive than overhead cable laying. Underground cable laying is more suitable when land is not available, and it also increases the aesthetics. This paper implements the automation on a manually operated cable pulling winch machine using programmable logic controller (PLC). Winch machines are useful in underground cable laying. The main aim of the project is to replace all the mechanical functions with electrical controls which are operated through a touch screen (HMI). The idea is that the machine should shift between parallel and series circuit automatically based on the pressure sensed instead of manually operating the solenoid valve. Traditional means of throttling the engine using lever and wire is replaced with a linear actuator. Sensors such as proximity, pressure and load sensor are used to provide the input to the system. The HMI used will display the speed, length and tension of the rope being winded. Ladder logic is used to program the PLC.