Journal articles on the topic 'Suppression des poudres à lever'
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1
Zhou, Yue-Qing, Lan-Yuan Zhang, Zhi-Peng Yu, Xiao-Qin Zhang, Jie Shi, and Hao-Wei Shen. "Tropisetron Facilitates Footshock Suppression of Compulsive Cocaine Seeking." International Journal of Neuropsychopharmacology 22, no. 9 (May 24, 2019): 574–84. http://dx.doi.org/10.1093/ijnp/pyz023.
Abstract:
AbstractBackgroundThe hallmark characteristics of the murine model of drug addiction include the escalation of cocaine consumption and compulsive punishment-resistant drug seeking. In this study, we evaluated the motivation for drug seeking in cocaine self-administering rats exposed to an escalated dosing regimen that endeavored to mimic the characteristic of escalating drug intake in human addicts. Tropisetron is a 5-HT3 receptor antagonist and α7-nicotinic receptor partial agonist. Utilizing rats trained on the escalated-dosing regimen, we examined the effects of tropisetron on control over compulsive drug-seeking behavior that was defined as footshock-resistant lever pressing.MethodsRats were trained to self-administer cocaine with incremental-infusion doses (from 0.6 to 2.4 mg/kg/infusion) across training sessions (3 h/session) or with a long-access paradigm (i.e., 0.6 mg/kg/infusion, 6 h/d training session). The drug-seeking motivations of 2 groups were estimated by the patterns of drug intake and progressive-ratio schedule. The compulsivity for drug seeking of the group with an escalated dose was further evaluated using the footshock-associated seeking-taking chain task.ResultsThe rats trained on the dose-escalated protocol achieved the same levels of motivated drug seeking as those subjected to a long-access paradigm, as indicated by cocaine intake per training session and breakpoints on a progressive ratio schedule. Tropisetron attenuated compulsive behavior of rats when pressing of the seeking lever potentially led to footshock. Intriguingly, tropisetron did not change the motivation to seek cocaine when footshock was absent. Tropisetron had no effect on locomotor activities or saccharin self-administration.ConclusionsThese results demonstrate that tropisetron restored control over compulsive cocaine seeking, and they indicate that 5-HT3/α7-nicotinic receptors may be potential therapeutic targets for relieving compulsive drug seeking.
2
Hou, Qun, Ya Ping Jin, and Yi Fan Zhou. "Electromagnetic Interference Testing and Suppression Methods for Automotive Window Lifter Motor." Applied Mechanics and Materials 433-435 (October 2013): 940–44. http://dx.doi.org/10.4028/www.scientific.net/amm.433-435.940.
Abstract:
Window lifter motor is one of the potential electromagnetic interference (EMI) sources in automobile. Based on the research on the principle of Window lifter motor and the generation mechanism of EMI, its EMI characteristics are tested and analyzed. The EMI suppression methods are proposed. By comparing two filters methods,it shows that the designed filter suppresses the electromagnetic interference more effectively. Its conducted emission and radiated emission are lower than the second lever limits of CISPR 25-2007+.
3
Liu, Xia, Tongyu Wang, Jinlong Liu, Jun Hou, Houjun Gai, Jie Yang, Zhenwen Sun, and Xiaochao Tian. "Design of a Flexible Hinged Piezoelectric Viscous Slip Actuator with Retraction Suppression." Journal of Nanoelectronics and Optoelectronics 18, no. 5 (May 1, 2023): 582–93. http://dx.doi.org/10.1166/jno.2023.3433.
Abstract:
In order to solve the displacement regression phenomenon of piezoelectric viscous-slip actuators, this paper proposes a lever-type flexible hinge mechanism that uses two sets of piezoelectric stacks to move the slider in both directions and efficiently suppress the displacement regression phenomenon. First, the overall dimensional parameters of the drive are designed, the device is modeled using 3D software, and the driving principle is analyzed. Then a theoretical model is built based on the lever amplification principle to derive the relevant expressions for the piezoelectric viscous slip actuator under sawtooth wave type voltage signals. The piezoelectric stack is simulated and analyzed with COMSOL Multiphysics to obtain the modal and stress-displacement clouds of the flexible hinges. Finally, a prototype was built for experimental testing, and the slider in the device was able to achieve smooth motion and effectively suppress the displacement regression phenomenon. The input voltage of piezo stack A is 100 V, the input voltage of piezo stack D is 150 V, the input frequency is 212 Hz, the maximum output displacement of single-step drive is 46.6 μm, and the amplification ratio of flexible hinge input to output is 2.59. The piezoelectric viscous-slip actuator was verified to be able to achieve effective drive and suppress back-off.
4
MITANI, KEIICHI. "Suppression of lever-pressing behavior in rats reared in differentially enriched environment." Japanese Psychological Research 35, no. 3 (1993): 119–28. http://dx.doi.org/10.4992/psycholres1954.35.119.
5
Sheng, Meng-jun, Di Lu, Zhi-ming Shen, and Mu-ming Poo. "Emergence of stable striatal D1R and D2R neuronal ensembles with distinct firing sequence during motor learning." Proceedings of the National Academy of Sciences 116, no. 22 (May 9, 2019): 11038–47. http://dx.doi.org/10.1073/pnas.1901712116.
Abstract:
The dorsolateral striatum (DLS) is essential for motor and procedure learning, but the role of DLS spiny projection neurons (SPNs) of direct and indirect pathways, as marked, respectively, by D1 and D2 receptor (D1R and D2R) expression, remains to be clarified. Long-term two-photon calcium imaging of the same neuronal population during mouse learning of a cued lever-pushing task revealed a gradual emergence of distinct D1R and D2R neuronal ensembles that reproducibly fired in a sequential manner, with more D1R and D2R neurons fired during the lever-pushing period and intertrial intervals (ITIs), respectively. This sequential firing pattern was specifically associated with the learned motor behavior, because it changed markedly when the trained mice performed other cued motor tasks. Selective chemogenetic silencing of D1R and D2R neurons impaired the initiation of learned motor action and suppression of erroneous lever pushing during ITIs, respectively. Thus, motor learning involves reorganization of DLS neuronal activity, forming stable D1R and D2R neuronal ensembles that fired sequentially to regulate different aspects of the learned behavior.
6
Aly Sayed Ahmed, A. M., Alberto Zasso, and Ferruccio Resta. "Proposed Configurations for the Use of Smart Dampers with Bracings in Tall Buildings." Smart Materials Research 2012 (February 6, 2012): 1–16. http://dx.doi.org/10.1155/2012/251543.
Abstract:
This paper presents wind-induced response reduction in a very slender building using smart dampers with proposed bracings-lever mechanism system. The building presents a case study of an engineered design that is instructive. The paper shows that shear response and flexural response of tall buildings present two very different cases for vibration suppression. Smart dampers are implemented optimally in the building to reduce its response in the lateral directions for both structural safety and occupant comfort concerns. New bracings-lever mechanism configurations are proposed for the dampers to improve their performance. The study shows how the proposed configurations can enable application to flexural response and scenarios where the interstory drift is not enough for dampers to work effectively. In addition, a decentralized bang-bang controller improved the performance of the smart dampers.
7
Liu, Chunchuan, Xingjian Jing, and Zhaobo Chen. "Band stop vibration suppression using a passive X-shape structured lever-type isolation system." Mechanical Systems and Signal Processing 68-69 (February 2016): 342–53. http://dx.doi.org/10.1016/j.ymssp.2015.07.018.
8
王, 海舟. "Transverse Vibration Suppression of Laminated Composite Beams with a Lever-Type Nonlinear Energy Sink." Open Journal of Acoustics and Vibration 12, no. 02 (2024): 63–75. http://dx.doi.org/10.12677/ojav.2024.122006.
9
Yamaguchi, Taku, Shigenori Watanabe, and Tsuneyuki Yamamoto. "Participation in arachidonic acid cascade of cannabinoid-induced suppression on lever-pressing behaviour in rats." Japanese Journal of Pharmacology 82 (2000): 61. http://dx.doi.org/10.1016/s0021-5198(19)47712-3.
10
Ó Drisceoil, Donal. "Keeping disloyalty within bounds? British media control in Ireland, 1914–19." Irish Historical Studies 38, no. 149 (May 2012): 52–69. http://dx.doi.org/10.1017/s0021121400000626.
Abstract:
Control over the media is a key lever of state power. During the First World War and immediate post-war period, British officials in Ireland exercised this power as they attempted to curtail radical Irish nationalism. While state control over the media can be wielded in direct form (usually through suppression), it frequently manifests itself more subtly and indirectly, through moderate censorship for example, especially when the state in question has a democratic dimension and liberal traditions or pretensions. In Ireland in the period covered by this article state interference with the media was both direct and indirect, partially mirroring the dual policy of coercion and conciliation that marked the final years of British governance over the whole island. Neither strategy succeeded in hobbling republican political advance, however, and censorship and suppression came to be regarded by radicals as irritants and obstacles that could be overcome.
11
Liesner, Marvin, and Wilfried Kunde. "Suppression of mutually incompatible proprioceptive and visual action effects in tool use." PLOS ONE 15, no. 11 (November 18, 2020): e0242327. http://dx.doi.org/10.1371/journal.pone.0242327.
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Movements of a tool typically diverge from the movements of the hand manipulating that tool, such as when operating a pivotal lever where tool and hand move in opposite directions. Previous studies suggest that humans are often unaware of the position or movements of their effective body part (mostly the hand) in such situations. It has been suggested that this might be due to a “haptic neglect” of bodily sensations to decrease the interference of representations of body and tool movements. However, in principle this interference could also be decreased by neglecting sensations regarding the tool and focusing instead on body movements. While in most tool use situations the tool-related action effects are task-relevant and thus suppression of body-related rather than tool-related sensations is more beneficial for successful goal achievement, we manipulated this task-relevance in a controlled experiment. The results showed that visual, tool-related effect representations can be suppressed just as proprioceptive, body-related ones in situations where effect representations interfere, given that task-relevance of body-related effects is increased relative to tool-related ones.
12
Ahlenius, Sven, and Jörgen Engel. "Potentiation by α-Methyltyrosine of the Suppression of Food-Reinforced Lever-Pressing Behaviour Induced by Antipsychotic Drugs." Acta Pharmacologica et Toxicologica 40, no. 1 (March 13, 2009): 115–25. http://dx.doi.org/10.1111/j.1600-0773.1977.tb02059.x.
13
Sawaguchi, T., I. Yamane, and K. Kubota. "Application of the GABA antagonist bicuculline to the premotor cortex reduces the ability to withhold reaching movements by well-trained monkeys in visually guided reaching task." Journal of Neurophysiology 75, no. 5 (May 1, 1996): 2150–56. http://dx.doi.org/10.1152/jn.1996.75.5.2150.
Abstract:
1. A gamma-aminobutyric acid (GABA) antagonist, bicuculline methiodide (BMI, 10 micrograms/microliters, 1 microliter), was locally injected into a total of 32 sites in the right premotor cortex (PM) of two rhesus monkeys that had been well-trained in a visually guided reaching task (VR) for approximately 3 yr. The monkey initiated the task by pressing a central hold lever with its left hand, and this was followed by waiting (1 s), warning (central green square on a computer monitor, 0.5 s), cue (right, upper, or left square), delay (2-5 s), and go (central green square changes to red, < 1.2 s) periods. In the go period, the monkey released the hold lever and reached out to one of three target levers (left, upper, or right) that had been indicated 2-5 s previously in the cue period. 2. At three sites in the dorsal part of the PM, after the local application of BMI, reaching movements of the left forelimb, which were not part of the trained-reaching, occurred 200-300 ms after the onset of a burst of neuronal activity at the BMI injection site. This induced-reaching, which was designated a "forced-reaching" movement, occurred while the monkeys were pressing the hold lever before the cue appeared-i.e., during the waiting or waiting period. No reaching occurred when the burst did not appear. Furthermore, trajectories and electromyograms of the forelimbs during the forced-reaching movements were similar to those in the trained-reaching movements in the VR task. 3. These results suggest that restricted sites in the dorsal PM of monkeys are involved in the initiation and/or execution of trained-reaching movements and that GABAergic inhibition at these sites normally suppresses this initiation/execution unless it is required. By relaxing GABAergic suppression, the dorsal PM might send a command to a neuronal system that is associated with trained reaching to recruit the system, thereby initiating and/or executing the trained reaching.
14
Trevitt, Jennifer. "SUBSTANTIA NIGRA PARS RETICULATA IS A VERY POTENT SITE FOR SUPPRESSION OF LEVER PRESSING AND LOCOMOTION BY SCH 23390." Behavioural Pharmacology 10, SUPPLEMENT 1 (August 1999): S94. http://dx.doi.org/10.1097/00008877-199908001-00240.
15
Zhang, Quan, Zhan Jiang, Xingfeng Yin, Liping Zhou, Xingyuan Li, Long Li, and Sicheng Yi. "Modelling and simulation of a novel secretary bird-inspired vibration isolator." Journal of Physics: Conference Series 2787, no. 1 (June 1, 2024): 012036. http://dx.doi.org/10.1088/1742-6596/2787/1/012036.
Abstract:
Abstract In this article, a novel secretary bird-inspired vibration isolator (SBIVI) is presented and investigated. The vibration isolator consists of an X-shaped stiffness adjustment mechanism and a lever arm structure that mimics the leg and wing of the secretary bird respectively. The biodynamics of the secretary bird is briefly introduced. The structure mapping from the body of the secretary bird to the scheme of the proposed SBIVI is analyzed. For the purpose of confirming the isolation performance of the SBIVI, the theoretical dynamics model is built while the virtual prototype simulation is carried out. By adjusting the values of the inertial mass and spring stiffness, the SBIVI can be easily installed with optimal operating conditions. From the simulation results, it is concluded that the vibration suppression ability of the SBIVI surpasses the traditional X-shaped structure within the interest of the frequency bandwidth.
16
Sato, T. "Effects of attention and stimulus interaction on visual responses of inferior temporal neurons in macaque." Journal of Neurophysiology 60, no. 1 (July 1, 1988): 344–64. http://dx.doi.org/10.1152/jn.1988.60.1.344.
Abstract:
1. Extracellular discharges were recorded from neurons in the inferior temporal cortex (area TE) of three macaque monkeys while they performed visual fixation and pattern discrimination tasks. For the pattern discrimination task, monkey was trained to release the lever quickly at the onset of one of two pattern stimuli and to release the lever at the dimming of the other pattern. During this task, neutral light stimulus (light bar) to which the monkey was not required to respond was presented once a trial either prior to the onset of the discriminandum or during presentation of the pattern that dimmed later. The neuronal activities evoked by the neutral stimulus under these two conditions were compared. 2. When the discriminanda were located at the center or at 5 degrees in the contralateral visual field, one-half of the neurons showed significantly smaller responses to the neutral stimulus when it was presented during presentation of the dimming pattern than when it was presented prior to the onset of the discriminandum. 3. The suppressive effect depended on the location of the two stimuli. When the neutral stimulus was located in the ipsilateral visual field and the pattern was located in the contralateral visual field, the response to the neutral stimulus was suppressed. However, when the pattern was located in the ipsilateral visual field (5 degrees visual angle), still within the receptive field for many neurons, the suppressive effect of the pattern on the response to the neutral stimulus in the contralateral visual field was almost undetectable. 4. When the pattern was located nearer the fovea than was the neutral stimulus, the suppressive effect was greater than when the pattern was located more peripherally to the neutral stimulus. Different from the receptive field of more primary visual neurons, this suppressive effect did not appear to be related to the neuron's responsiveness to the patterns nor to precise stimulus location in the receptive field. 5. The magnitude of suppression by the attended pattern on the visual response during the pattern discrimination task correlated with the suppression noted in the presence of a fixation spot during the fixation tasks, while the animals did not fixate on the attended pattern. The response of some neurons to the neutral stimulus prior to pattern presentation during the pattern discrimination task was enhanced slightly compared with the response recorded during the simple fixation task.(ABSTRACT TRUNCATED AT 400 WORDS)
17
Ren, Yixin, Hoku West-Foyle, Alexandra Surcel, Christopher Miller, and Douglas N. Robinson. "Genetic suppression of a phosphomimic myosin II identifies system-level factors that promote myosin II cleavage furrow accumulation." Molecular Biology of the Cell 25, no. 25 (December 15, 2014): 4150–65. http://dx.doi.org/10.1091/mbc.e14-08-1322.
Abstract:
How myosin II localizes to the cleavage furrow in Dictyostelium and metazoan cells remains largely unknown despite significant advances in understanding its regulation. We designed a genetic selection using cDNA library suppression of 3xAsp myosin II to identify factors involved in myosin cleavage furrow accumulation. The 3xAsp mutant is deficient in bipolar thick filament assembly, fails to accumulate at the cleavage furrow, cannot rescue myoII-null cytokinesis, and has impaired mechanosensitive accumulation. Eleven genes suppressed this dominant cytokinesis deficiency when 3xAsp was expressed in wild-type cells. 3xAsp myosin II's localization to the cleavage furrow was rescued by constructs encoding rcdBB, mmsdh, RMD1, actin, one novel protein, and a 14-3-3 hairpin. Further characterization showed that RMD1 is required for myosin II cleavage furrow accumulation, acting in parallel with mechanical stress. Analysis of several mutant strains revealed that different thresholds of myosin II activity are required for daughter cell symmetry than for furrow ingression dynamics. Finally, an engineered myosin II with a longer lever arm (2xELC), producing a highly mechanosensitive motor, could also partially suppress the intragenic 3xAsp. Overall, myosin II accumulation is the result of multiple parallel and partially redundant pathways that comprise a cellular contractility control system.
18
Moorman, David E., and Gary Aston-Jones. "Prefrontal neurons encode context-based response execution and inhibition in reward seeking and extinction." Proceedings of the National Academy of Sciences 112, no. 30 (July 13, 2015): 9472–77. http://dx.doi.org/10.1073/pnas.1507611112.
Abstract:
The prefrontal cortex (PFC) guides execution and inhibition of behavior based on contextual demands. In rodents, the dorsal/prelimbic (PL) medial PFC (mPFC) is frequently considered essential for execution of goal-directed behavior (“go”) whereas ventral/infralimbic (IL) mPFC is thought to control behavioral suppression (“stop”). This dichotomy is commonly seen for fear-related behaviors, and for some behaviors related to cocaine seeking. Overall, however, data for reward-directed behaviors are ambiguous, and few recordings of PL/IL activity have been performed to demonstrate single-neuron correlates. We recorded neuronal activity in PL and IL during discriminative stimulus driven sucrose seeking followed by multiple days of extinction of the reward-predicting stimulus. Contrary to a generalized PL-go/IL-stop hypothesis, we found cue-evoked activity in PL and IL during reward seeking and extinction. Upon analyzing this activity based on resultant behavior (lever press or withhold), we found that neurons in both areas encoded contextually appropriate behavioral initiation (during reward seeking) and withholding (during extinction), where context was dictated by response–outcome contingencies. Our results demonstrate that PL and IL signal contextual information for regulation of behavior, irrespective of whether that involves initiation or suppression of behavioral responses, rather than topographically encoding go vs. stop behaviors. The use of context to optimize behavior likely plays an important role in maximizing utility-promoting exertion of activity when behaviors are rewarded and conservation of energy when not.
19
Arizzi, M. N., K. M. Cervone, J. E. Aberman, A. Betz, Q. Liu, S. Lin, A. Makriyannis, and J. D. Salamone. "Behavioral effects of inhibition of cannabinoid metabolism: The amidase inhibitor AM374 enhances the suppression of lever pressing produced by exogenously administered anandamide." Life Sciences 74, no. 8 (January 2004): 1001–11. http://dx.doi.org/10.1016/j.lfs.2003.07.024.
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Behera, Swagat Ranjan, Riya Pandey, Krisanu Golui, Swapnashree Sahoo, Riya Jakhwal, and Riti Pal. "Application of Panchagavya, a Cow-based Liquid Formulation, as a Lever for Sustainable and Enhanced Vegetable Crop Production: A Review." International Journal of Environment and Climate Change 14, no. 5 (May 18, 2024): 214–32. http://dx.doi.org/10.9734/ijecc/2024/v14i54183.
Abstract:
Panchagavya, a fermented liquid bio-formulation derived from cow-based products such as dung, urine, milk, curd and ghee, has recently gained importance in agricultural practices due to its reported effectiveness in enhancing vegetable crop production. Its formulation involves a fermentation process that harnesses the diverse microbial communities present in cow-derived substances, resulting in a potent nutrient-rich solution that is believed to possess plant growth-promoting properties. One of the primary mechanisms underlying its efficacy lies in the diverse array of microorganisms present in the formulation. These microorganisms, including beneficial bacteria, fungi and actinomycetes, play crucial roles in nutrient cycling, disease suppression and soil conditioning. Additionally, Panchagavya contains plant growth-promoting substances such as hormones, enzymes, vitamins and amino acids, which contribute to enhanced nutrient uptake, root development and overall plant vigour. Furthermore, application of Panchagavya has been shown to improve soil health by enhancing microbial activity, increasing organic matter content and improving soil properties. These soil improvements not only benefit the current crop but also have long-term positive implications for soil fertility and sustainability. This multifaceted approach to crop management offers a holistic solution to enhance crop productivity while reducing reliance on synthetic inputs. This review aims to comprehensively analyse the literature on the effects of Panchagavya on vegetable crops, highlighting its mechanisms of action and potential benefits for increased vegetable crop production.
21
Yoshida, Keitaro, Michael R. Drew, Anna Kono, Masaru Mimura, Norio Takata, and Kenji F. Tanaka. "Chronic social defeat stress impairs goal-directed behavior through dysregulation of ventral hippocampal activity in male mice." Neuropsychopharmacology 46, no. 9 (March 10, 2021): 1606–16. http://dx.doi.org/10.1038/s41386-021-00990-y.
Abstract:
AbstractChronic stress is a risk factor for a variety of psychiatric disorders, including depression. Although impairments to motivated behavior are a major symptom of clinical depression, little is known about the circuit mechanisms through which stress impairs motivation. Furthermore, research in animal models for depression has focused on impairments to hedonic aspects of motivation, whereas patient studies suggest that impairments to appetitive, goal-directed motivation contribute significantly to motivational impairments in depression. Here, we characterized goal-directed motivation in repeated social defeat stress (R-SDS), a well-established mouse model for depression in male mice. R-SDS impaired the ability to sustain and complete goal-directed behavior in a food-seeking operant lever-press task. Furthermore, stress-exposed mice segregated into susceptible and resilient subpopulations. Interestingly, susceptibility to stress-induced motivational impairments was unrelated to stress-induced social withdrawal, another prominent effect of R-SDS in mouse models. Based on evidence that ventral hippocampus (vHP) modulates sustainment of goal-directed behavior, we monitored vHP activity during the task using fiber photometry. Successful task completion was associated with suppression of ventral hippocampal neural activity. This suppression was diminished after R-SDS in stress-susceptible but not stress-resilient mice. The serotonin selective reuptake inhibitor (SSRI) escitalopram and ketamine both normalized vHP activity during the task and restored motivated behavior. Furthermore, optogenetic vHP inhibition was sufficient to restore motivated behavior after stress. These results identify vHP hyperactivity as a circuit mechanism of stress-induced impairments to goal-directed behavior and a putative biomarker that is sensitive to antidepressant treatments and that differentiates susceptible and resilient individuals.
22
Fujii, Masaya, Mitsuyo Asada, Nanae Takata, Akira Yamano, and Hiroshi Imada. "Measurement of emotional reactivity and association ability of the Tsukuba emotional strains of rats (Rattus norvegicus) in licking and lever-pressing conditioned suppression situations." Journal of Comparative Psychology 103, no. 1 (1989): 100–108. http://dx.doi.org/10.1037/0735-7036.103.1.100.
23
Li, Jianying, Lingbing Kong, Heng Liang, Weidong Li, and Saad Aldosary. "Enhancing Electro-Hydraulic Load Simulator Performance Through Variable Arm Length and Particle Swarm-Optimized Controllers." Journal of Nanoelectronics and Optoelectronics 18, no. 9 (September 1, 2023): 1085–99. http://dx.doi.org/10.1166/jno.2023.3490.
Abstract:
This study presents a novel approach to improve the loading characteristics of an electro-hydraulic load simulator by introducing a variable arm length mechanism and employing advanced control strategies rooted in Particle Swarm Optimization (PSO). The design enhancements focus on optimizing the physical connection between the steering gear system and the load system, resulting in an electro-hydraulic load simulator equipped with adjustable arm length. Through a meticulous analysis of the ideal pivot position for the rocker lever, a fuzzy Proportional-Integral-Derivative (PID) controller based on PSO has been developed for the steering gear system. In recognition of the PSO algorithm’s susceptibility to local optima convergence, a fuzzy PID controller employing Single-Particle Random Search (SSPSO) has also been devised for the load system. To assess the effectiveness of this innovative hardware configuration and controller implementation in mitigating over-suppression, comprehensive joint simulation experiments were conducted. The results unequivocally indicate that the incorporation of the variable arm length structure, along with the PSO-based fuzzy PID controller optimized using binding factors, substantially enhances the dynamic loading performance of the electro-hydraulic load simulator. This enhancement translates into superior loading accuracy and overall performance metrics, establishing this research as a valuable reference for future investigations in this field.
24
Sakaguchi, Masakiyo, Hitoshi Murata, Hiroyuki Sonegawa, Yoshihiko Sakaguchi, Jun-ichiro Futami, Midori Kitazoe, Hidenori Yamada, and Nam-ho Huh. "Truncation of Annexin A1 Is a Regulatory Lever for Linking Epidermal Growth Factor Signaling with Cytosolic Phospholipase A2 in Normal and Malignant Squamous Epithelial Cells." Journal of Biological Chemistry 282, no. 49 (October 10, 2007): 35679–86. http://dx.doi.org/10.1074/jbc.m707538200.
Abstract:
Regulation of cell growth and apoptosis is one of the pleiotropic functions of annexin A1 (ANXA1). Although previous reports on the overexpression of ANXA1 in many human cancers and on growth suppression and/or induction of apoptosis by ANXA1 may indicate the tumor-suppressive nature of ANXA1, molecular mechanisms of the function of ANXA1 remain largely unknown. Here we provide evidence that ANXA1 mechanistically links the epidermal growth factor-triggered growth signal pathway with cytosolic phospholipase A2 (cPLA2), an initiator enzyme of the arachidonic acid cascade, through interaction with S100A11 in normal human keratinocytes (NHK). Ca2+-dependent binding of S100A11 to ANXA1 facilitated the binding of the latter to cPLA2, resulting in inhibition of cPLA2 activity, which is essential for the growth of NHK. On exposure of NHK to epidermal growth factor, ANXA1 was cleaved solely at Trp12, and this cleavage was executed by cathepsin D. In squamous cancer cells, this pathway was shown to be constitutively activated. The newly found mechanistic intersection may be a promising target for establishing new measures against human cancer and other cell growth disorders.
25
Presby, Rose E., Renee A. Rotolo, Erin M. Hurley, Sarah M. Ferrigno, Cayla E. Murphy, Haley P. McMullen, Pranally A. Desai, et al. "Sex differences in lever pressing and running wheel tasks of effort-based choice behavior in rats: Suppression of high effort activity by the serotonin transport inhibitor fluoxetine." Pharmacology Biochemistry and Behavior 202 (March 2021): 173115. http://dx.doi.org/10.1016/j.pbb.2021.173115.
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Scott, Karen A., and Timothy H. Moran. "The GLP-1 agonist exendin-4 reduces food intake in nonhuman primates through changes in meal size." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 293, no. 3 (September 2007): R983—R987. http://dx.doi.org/10.1152/ajpregu.00323.2007.
Abstract:
Exendin-4 (Ex4), a long-acting glucagon-like peptide-1 (GLP-1) receptor agonist, has been shown to reduce food intake and suppress gastric emptying in rodents and humans. In this study we investigated the effects of peripheral administration of Ex4 on food intake and meal patterns in adult male rhesus macaques. Rhesus macaques ( n = 4) that had been trained to lever press for food pellets were injected intramuscularly 15 min before the start of their 6-h daily feeding period. Ex4 was given at doses of 0.10, 0.32, 0.56, 1.0, and 3.0 μg/kg. Ex4 suppressed food intake in a dose-dependent manner, with the 3.0 μg/kg dose completely preventing feeding during the 6-h period and the 0.10 μg/kg dose suppressing intake by 17%. Doses of 0.32, 0.56, 1.0, and 3.0 μg/kg caused significant reductions in cumulative intake at all six hourly time points. Ex4 inhibited food intake through a specific effect on meal size. Meal size was significantly reduced in a dose-dependent manner with significant reductions at the 0.32 and 1.0 μg/kg doses ( P < 0.05). Day 2 and 3intakes returned to baseline levels with no compensation for Ex4-induced feeding suppression. Administration of doses of 0.32 and 0.56 μg/kg Ex4 over 5 consecutive days led to sustained reductions in intake with no evidence of compensation. Again, these reductions were due to specific effects on meal size. These results demonstrate that activation of GLP-1 pathways has potent effects on the controls of meal size and overall food intake in a nonhuman primate model.
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Hosseini Rad, A., G. Min Yi Tan, A. Poudel, and A. McLellan. "P06.02 Enhancing CAR T cell persistence and memory through modulating mitochondrial function." Journal for ImmunoTherapy of Cancer 8, Suppl 2 (October 2020): A42.1—A42. http://dx.doi.org/10.1136/jitc-2020-itoc7.81.
Abstract:
BackgroundCAR T cell therapy for solid tumours has achieved limited success compared to its application to B cell malignancies. One reason for this failure is the low differentiation rate to memory subsets and low persistence of CAR T cells due to activation-induced cell death (AICD) in lymphoid tissue and the tumour microenvironment. In this study, we have expressed the MCL1 gene within CAR T cells to overcome losses by AICD in adoptively transferred T cells. The MCL1 gene expresses two isoforms; the long isoform localises to the outer membrane of mitochondria and inhibits the CD95 signalling death pathway, while the short isoform localises to the inner membrane of mitochondria to enhance mitochondrial oxidation, phosphorylation and fusion. In addition, we have also utilized a microRNA (miR) 429 to promote memory T cell formation through the suppression of genes such as T-cell-restricted intracellular antigen-1 (TIA-1), T cell activation inhibitor, mitochondrial (TCAIM) and mitochondrial fission factor (MFF).Materials and MethodsOverexpression of MCL1 was confirmed at both mRNA and protein level by real time RT-PCR (qPCR) and western blot. Similarly, overexpression of miR-429 was measured by qPCR and specific binding of miR-429 to the 3′ UTR of target genes was confirmed by luciferase reporter assay. Mitochondrial depolarization and cell viability were assessed by TMRE mitochondrial membrane potential assay (flow-cytometry) and resazurin assay. The effect of MCL1 or miR429 overexpression on HER2-CAR T cells was determined by flow cytometry. Soluble leucine-zipper CD95L (https://www.addgene.org/104349/) was expressed and purified from Expi293 cells.ResultsOverexpression of MCL1 in both Jurkat T cells and primary human T cells protected cells against mitochondria depolarization as well as the loss of cell viability in response to CD95L-triggering. Expression of miR429 downregulated TIA1, TCAIM and MFF. A HER2-CAR construct with either MCL1 or miR429 in a lentiviral system was successfully designed and transduced into primary T cells. Mitochondria in transduced T demonstrated enlarged and fusion morphology - a classic feature of memory T cells.ConclusionsOverexpressing MCL1 or miR429 significantly improves mitochondrial function in T cells. This approach will be used to increase persistence of adoptively transferred CAR T cells.Disclosure InformationA. Hosseini Rad: None. G. Min Yi Tan: None. A. Poudel: None. A. McLellan: None.
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Sukhodoev, V. N. "Rail Track with Rail Compression." Science & Technique 20, no. 3 (June 3, 2021): 234–42. http://dx.doi.org/10.21122/2227-1031-2021-20-3-234-242.
Abstract:
The problem of damping the noise on the track, arising from the movement of the train, is solved sufficiently but it is simple, if the rail with spacers is laid inside the longitudinally located band sleeper-mechanism. The result is a layered rail thread, consisting of belts: a rail tape with elastic spacers on three sides, a tie-mechanism tape and a ballast layer. The unity of the layers is carried out due to their own mass. This is the static track without external load. Rail compression is an effective property of rail tracks. It is formed in the sleeper mechanism under the influence of vertical forces with displacements and their horizontal derivatives. When loading the track, the compression is carried out repeatedly with subsequent unloading.n this case, each previous changes in the conditions in work of the track are taken into account in the subsequent cycle of loading and unloading. A rail track with a rail compression is a kind of self-adapting linear system, which is necessary with frequent changes in load and operating conditions for silent performance of a functional purpose. The specificity of this path is that the movement of the wheel creates rail vibration and noise, which are immediately damped by compression with damping. The balance between the occurrence of noise and its suppression is achieved by the ratio of the lengths of half-sleeper shoulders as a lever. The condition for the appearance of a shift of the compression forces in the direction from vertical shoulder of the half-sleepers is the unequal settlements of the horizontal shoulder of the L-shaped half-sleepers and its eccentric loading. As a result of the research, the advantages of a rail track with rail compression have been revealed, which is a guarantor of the stability of the design parameters during long-term operation of the track. The cost of a rail track with rail reduction is halved as a result of steel savings, lower labor costs and operational needs.
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Poudel, A., SM Rad, G. Tan, and AD McLellan. "P06.04 Enhancing T cell function for cancer immunotherapy by microRNA mediated knockdown of PRKAR1A." Journal for ImmunoTherapy of Cancer 8, Suppl 2 (October 2020): A43.1—A43. http://dx.doi.org/10.1136/jitc-2020-itoc7.83.
Abstract:
BackgroundProtein Kinase A (PKA) is a heterotetramer holoenzyme that consists of two regulatory and catalytic subunits. During T cell activation, one of the regulatory subunits (PRKAR1A) localizes to the immune synapse, inhibiting several central proteins in the T-cell signalling cascade and leading to T cell inactivation. Previously, the disruption of localisation of PKA type I R1α (PRKAR1A) to the immune synapse using disruptor peptides has been shown to improve chimeric antigen receptor (CAR) T cell function.1 2 However, the effect of PRKAR1A knockdown in T cells (including CAR T cells) has not been studied yet. In this study, we have utilized microRNAs (miR); miR96/183 or miR155 to knockdown PRKAR1A and explored the advantages of PRKAR1A knockdown on T cell activation and function.Materials and MethodsMicroRNAs (miR); miR96/183 or miR155 were cloned from human genomic DNA into a sleeping beauty system under a doxycycline inducible promoter (TCE). Overexpression of miRNA and target knockdown was assessed at both transcript level (by real time RT-PCR) and/or protein level (by western blot) respectively while target validation was done by luciferase assay. The fate of PRKAR1A knockdown on Jurkat T cells activated with anti-CD3 and anti-CD28 antibodies were determined by measuring IL-2 production (ELISA) and CD69 surface expression (flow cytometry). The effect of miR96/183 or miR155 overexpression in primary T cells expressing HER2-CAR were also compared.ResultsWe efficiently overexpressed both miRNAs and downregulated PRKAR1A expression in HEK293 cells at both mRNA and protein level. Luciferase assay confirmed miRNA mediated specific knockdown of PRKAR1A; mutated 3’UTR of PRKAR1A was used as negative control. Overexpression of miRNAs also downregulated PRKAR1A expression in Jurkat cells which resulted in enhanced activation (CD69 expression) and IL-2 production following anti-CD3/CD28 stimulation compared to untransfected controls (with normal PRKAR1A expression). Additionally, miRNA 96/183 and miRNA155 were found to target inhibitory proteins of TCR signalling such as CTLA4, Foxo3 and ptpn2 and resulted in superior T cell function. A third-generation lentiviral system has been optimised to express either miR96/183 or miR155 and HER2-CAR in the same vector and currently we are assessing the effect of PRKAR1A knockdown on primary CAR T cells.ConclusionsOverexpressing miRNA for knockdown of inhibitory proteins could be an efficient way of enhancing T cell function against solid tumours. Additionally, co-expressing CAR and miRNAs using lentiviral system would benefit such approaches for cancer immunotherapy.ReferencesNewick K, O’ Brien S, Sun J, Kappor V, Maceyko S, Lo A, Pure E, Moon E, Albelda SM. Augmentation of CAR T cell trafficking and antitumour efficacy by blocking protein kinase A (PKA) localization. Cancer Immunol Res 2016; 4(6): 541–551Hussain M, Shah Z, Abbas N, Javeed A, Mukhtar MM, Zhang J. Targeting tumour-associated immune suppression with selective protein kinase A type I (PKAI) inhibitors may enhance cancer immunotherapy. Medical Hypotheses 2016;86: 56–59Disclosure InformationA. Poudel: None. S.M. Rad: None. G. Tan: None. A.D. McLellan: None.
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Bushnell, Philip J. "Styrene Impairs Serial Spatial Reversal Learning in Rats." Journal of the American College of Toxicology 13, no. 4 (August 1994): 279–300. http://dx.doi.org/10.3109/10915819409140600.
Abstract:
To evaluate the effects of styrene exposure on learning, adult male Long-Evans rats learned repeated reversals of a spatial discrimination task. Styrene monomer (50% vol/vol in corn oil) was administered by gavage to groups of eight rats at 500 mg/kg/day, 5 days/week, for 8 weeks in Experiments (Exps) I and II (total dose = 20.0 g/kg) or for 1,3,5, or 8 weeks in Exp III (total dose = 2.5, 7.5, 12.5, or 20.0 g/kg). Control rats received corn oil vehicle for 8 weeks. Reversal training began 8 (Exp I), 10 (Exp II), or 32 (Exp III) weeks after termination of dosing. In Exp I, an instrumental (IN) schedule was used, under which rats received food after each presentation of a “positive” response lever (S+ ) only if they had made at least one response during that presentation of S+. In Exps II and III, an automaintenance (AU) schedule was used, under which rats received food after every presentation of S+, regardless of responding. In all experiments, a second manipulandum (S°) was presented randomly in time with respect to S + and food delivery. A discrimination ratio (DR) was calculated as the proportion of total responses on S+ in each block of 10 trials. A reversal involved switching the reward values of S+ and S°. Serial reversal learning was quantified in terms of trials to criterion. Reversal learning improved similarly in control and treated rats trained under the IN schedule, whereas treated rats trained under the AU schedule failed to improve as much as controls. Reversal learning of some styrene-treated AU rats in Exp III continued to be impaired for > 1 year after treatment. Increased responding on S° featured prominently in the behavioral effect of styrene. An IN schedule requiring suppression of S° responses for food in Exp III revealed a clear deficit in rats exposed to styrene. Not all treated rats were affected by styrene; nevertheless, changes in the affected individuals were as large as those previously observed after trimethyltin-induced lesions of the CNS. The incidence of impairment was not related to the total dose of styrene given, suggesting the action of other, undetermined factors affecting individual sensitivity to styrene.
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Budiarto, Hairil, Vivi Triwidyaningrum, Faikul Umam, and Ach Dafid. "Implementation of Automatic DC Motor Braking PID Control System on (Disc Brakes)." Journal of Robotics and Control (JRC) 4, no. 3 (June 6, 2023): 371–87. http://dx.doi.org/10.18196/jrc.v4i3.18505.
Abstract:
The vital role of an automated braking system in ensuring the safety of motorized vehicles and their passengers cannot be overstated. It simplifies the braking process during driving, enhancing control and reducing the chances of accidents. This study is centered on the design of an automatic braking device for DC motors utilizing disc brakes. The instrument employed in this study was designed to accelerate the vehicle in two primary scenarios - before the collision with an obstacle and upon crossing the safety threshold. It achieves this by implementing the Proportional Integral Derivative (PID) control method. A significant part of this system comprises ultrasonic sensors, used for detecting the distance to obstructions, and rotary encoder sensors, which are utilized to measure the motor's rotational speed. These distance and speed readings serve as essential reference points for the braking process. The system is engineered to initiate braking when the distance value equals or falls below 60cm or when the speed surpasses 8000rpm. During such events, the disc brake is activated to reduce the motor's rotary motion. The suppression of the disc brake lever is executed pneumatically, informed by the sensor readings. Applying the PID method to the automatic braking system improved braking outcomes compared to a system without the PID method. This was proven by more effective braking results when the sensors detected specific distance and speed values. Numerous PID tuning tests achieved optimal results with K_p = 5, K_i = 1, and K_d = 3. These values can be integrated into automatic braking systems for improved performance. The PID method yielded more responsive braking outcomes when applied in distance testing. On the contrary, the braking results were largely unchanged in the absence of PID. Regarding speed testing, the PID method significantly improved the slowing down of the motor speed when it exceeded the maximum speed limit of 8000 rpm. This eliminates the possibility of sudden braking, thus maintaining the system within a safe threshold. The average time taken by the system to apply braking was 01.09 seconds, an indication of its quick responsiveness. This research is a valuable addition to control science, applying the PID control method to automatic DC motor braking. It provides valuable insights and concrete applications of PID control to complex mechatronic systems. It is also noteworthy for its development and optimization of suitable PID parameters to achieve responsive and stable braking. The study, therefore, offers a profound understanding of how PID control can be employed to manage braking systems on automatic DC motors, thereby advancing knowledge and application of control in control science and mechatronics.
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Mayer, Paulo César Morales, and Marcus Bentes De Carvalho Neto. "A SYSTEMATIC REPLICATION OF SKINNER (1938) USING A HOT AIR BLAST AS THE PUNISHER." Revista Brasileira de Análise do Comportamento 12, no. 2 (May 23, 2017). http://dx.doi.org/10.18542/rebac.v12i2.4405.
Abstract:
The present study was a systematic replication of the classic study by Skinner (1938) using a hot air blast (HAB) as the punisher. After lever press training, six rats underwent two extinction sessions. During the initial 10 min of extinction in the first session, half of the subjects received a HAB for every lever press (punishment). Subjects that received punishment made fewer lever presses during first extinction session, but the total number of responses in both groups was equivalent by the end of the second extinction session. The present data corroborate the findings of Skinner (1938) that the punishment may have partial and temporary effects in certain contexts. We discuss the ways in which the elicitation of competitive responses, the intensity and nature of the stimulus, and the duration of exposure to the aversive contingency are important factors that may explain the divergent results in the literature.Keywords: punishment, replication, competitive responses, suppression, rats, hot air blast
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Bertolus, Julie Boulanger, Jeroen Knippenberg, Anna Verschueren, Pascale Le Blanc, Bruce L. Brown, Anne-Marie Mouly, and Valérie Doyère. "Temporal Behavior in Auditory Fear Conditioning: Stimulus Property Matters." International Journal of Comparative Psychology 28 (2015). http://dx.doi.org/10.46867/ijcp.2015.28.02.04.
Abstract:
The accuracy of time judgments depends upon many factors, including the sensory properties of the to-be-timed stimulus. In auditory Pavlovian fear conditioning, an initially neutral tone (conditioned stimulus, CS) predicts the arrival of an aversive event (unconditioned stimulus, US) at a fixed time interval. The temporal relation between the CS and US events is encoded, leading to the development of a temporal pattern of responding. Little attention has been paid to the potential impact of the characteristics of the CS tone on the development of this temporal pattern. Here we compared the acquisition of the temporal pattern of conditioned responses of rats to different CS tone frequencies. Rats were first conditioned to lever press for food. Then, while lever pressing for food, they were presented with 60-s tones of two very different frequencies 1kHz or 11kHz, each paired with a foot-shock given 30s after tone onset. This fear conditioning led to the appearance of conditioned suppression of the lever pressing. On probe trials the tone duration was 60 s, and the reinforcer was omitted. With training, a pattern of suppression evolved during the probe trials, showing a maximum of suppression near the programmed time of the shock US, however the 11kHz CS tone yielded better temporal control than did the 1kHz tone. A second experiment investigated rats’ abilities to discriminate between two times of shock arrival (10s or 30s) predicted by the different tone frequencies (1kHz or 11kHz), In this experiment, rats showed poorer discriminative timing performance when the lower frequency (1kHz) was associated with the longer duration (30s). Our results suggest a strong impact of the CS sensory properties on the expression of temporal learning within the context of auditory fear conditioning in rats.
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Florczynski, Matthew. "4. Differential Impairments in Incentive Learning Caused by First‐ and Second‐ Generation Antipsychotic Drugs." Inquiry@Queen's Undergraduate Research Conference Proceedings, February 5, 2016. http://dx.doi.org/10.24908/iqurcp.8466.
Abstract:
Schizophrenia is a neuropsychiatric disorder characterized by increased function of dopamine in the brain. Dopamine release is a natural response to reward. It promotes incentive learning (IL), a process by which neutral stimuli acquire the ability to elicit approach and other responses. A recent model characterizes dopamine‐mediated IL as a progressive process with early and late stages accompanied by a shift in neural control from the nucleus accumbens (NAc) to the dorsolateral striatum (DLS). A parallel can be drawn to differences in regionally specific neural responses generated by first‐ and second‐generation antipsychotic drugs (APDs) used to treat schizophrenia. APDs are dopamine receptor antagonists, but first‐generation APDs affect the NAc and DLS while second‐generation APDs affect primarily the NAc. We compared the effects of APDs on IL. Rats (N = 48) were trained to press a lever for food pellets in an operant chamber. Intraperitoneal injections (1 hr before testing) of the first‐generation APD haloperidol (0,0.05,0.10,0.20 mg/kg) or of the second‐generation APD risperidone (0,0.20,0.40,0.80 mg/kg) induced dose‐dependent suppression of lever pressing on days 1‐4, with the highest dose groups failing to demonstrate any evidence of previous learning on day 5 when tested drug‐free. On days 16‐20, haloperidol induced a day‐to‐day suppression not seen with risperidone. The results suggest that the effects of first‐ and second‐generation APDs on learning processes putatively mediated by the NAc and DLS can be differentiated experimentally. The findings imply that APDs may differentially affect IL inpatients with schizophrenia.
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Florczynski, Matthew. "Differential Impairments in Incentive Learning Caused by First‐ and Second‐ Generation Antipsychotic Drugs." Inquiry@Queen's Undergraduate Research Conference Proceedings, February 5, 2016. http://dx.doi.org/10.24908/iqurcp.8367.
Abstract:
Schizophrenia is a neuropsychiatric disorder characterized by increased function of dopamine in the brain. Dopamine release is a natural response to reward. It promotes incentive learning (IL), a process by which neutral stimuli acquire the ability to elicit approach and other responses. A recent model characterizes dopamine‐mediated IL as a progressive process with early and late stages accompanied by a shift in neural control from the nucleus accumbens (NAc) to the dorsolateral striatum (DLS). A parallel can be drawn to differences in regionally specific neural responses generated by first‐ and second‐generation antipsychotic drugs (APDs) used to treat schizophrenia. APDs are dopamine receptor antagonists, but first‐generation APDs affect the NAc and DLS while second‐generation APDs affect primarily the NAc. We compared the effects of APDs on IL. Rats (N = 48) were trained to press a lever forfood pellets in an operant chamber. Intraperitoneal injections (1 hr before testing) of the first‐generation APD haloperidol (0,0.05,0.10,0.20 mg/kg) or of the second‐generation APD risperidone (0,0.20,0.40,0.80 mg/kg) induced dose‐dependent suppression of lever pressing on days 1‐4, with the highest dose groups failing to demonstrate any evidence of previous learning on day 5 when tested drug‐free. On days 16‐20 haloperidol induced a day‐to‐day suppression not seen with risperidone. The results suggest that the effects of first‐ and second‐generation APDs on learning processes putatively mediated by the NAc and DLS can be differentiated experimentally. The findings imply that APDs may differentially affect IL inpatients with schizophrenia.
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Menalled, Uriel D., Sarah J. Pethybridge, Chris J. Pelzer, Richard G. Smith, Antonio DiTommaso, and Matthew R. Ryan. "High Seeding Rates and Low Soil Nitrogen Environments Optimize Weed Suppression and Profitability in Organic No-Till Planted Soybean." Frontiers in Agronomy 3 (May 7, 2021). http://dx.doi.org/10.3389/fagro.2021.678567.
Abstract:
No-till planting crops into rolled-crimped cover crops can improve soil health while reducing labor and fuel requirements compared with traditional tillage-based production. However, little information is available to help farmers optimize the management of organic no-till planted crops. Weed suppression, crop yield, and profitability were assessed across soybean [Glycine max (L.) Merr.] seeding rates and soil nitrogen environments in an experiment conducted at two sites in central New York. Soybeans were no-till planted into rolled-crimped cereal rye (Secale cereale L.) at 0, 185,000, 371,000, 556,000, and 741,000 seeds ha−1. Three rates (0, 63, or 125 kg ha−1) of sodium nitrate (15-0-2) were applied across seeding rates to create different soil nitrogen environments. When pooled over sites, the lowest weed biomass occurred at the highest soybean density in the lowest soil nitrogen environment. An interaction was observed between soybean seeding rate and nitrogen treatments on weed communities. Soybean yield increased asymptotically with crop density and was not affected by nitrogen or site treatments. When pooled over nitrogen treatments and sites, partial returns to the soybean seeding rates were maximized at $2,238 ha−1 with 527,800 seeds ha−1. Results suggest that crop density is an important lever for optimizing weed suppression and crop yield in organic no-till soybean, and that managing for low soil nitrogen conditions may further enhance weed suppression while maintaining high yields.
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Lu, Shen-zhao, Yue Wu, Yong-shun Guo, Pei-zhou Liang, Shu Yin, Yan-qing Yin, Xiu-li Zhang, et al. "Inhibition of astrocytic DRD2 suppresses CNS inflammation in an animal model of multiple sclerosis." Journal of Experimental Medicine 219, no. 9 (July 25, 2022). http://dx.doi.org/10.1084/jem.20210998.
Abstract:
Astrocyte activation is associated with progressive inflammatory demyelination in multiple sclerosis (MS). The molecular mechanisms underlying astrocyte activation remain incompletely understood. Recent studies have suggested that classical neurotransmitter receptors are implicated in the modulation of brain innate immunity. We investigated the role of dopamine signaling in the process of astrocyte activation. Here, we show the upregulation of dopamine D2 receptor (DRD2) in reactive astrocytes in MS brain and noncanonical role of astrocytic DRD2 in MS pathogenesis. Mice deficient in astrocytic Drd2 exhibit a remarkable suppression of reactive astrocytes and amelioration of experimental autoimmune encephalomyelitis (EAE). Mechanistically, DRD2 regulates the expression of 6-pyruvoyl-tetrahydropterin synthase, which modulates NF-κB activity through protein kinase C-δ. Pharmacological blockade of astrocytic DRD2 with a DRD2 antagonist dehydrocorybulbine remarkably inhibits the inflammatory response in mice lacking neuronal Drd2. Together, our findings reveal previously an uncharted role for DRD2 in astrocyte activation during EAE-associated CNS inflammation. Its therapeutic inhibition may provide a potent lever to alleviate autoimmune diseases.
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Duan, Ningyuan, Haiting Yu, Zhenguo Zhang, and Hongxing Hua. "Study on the hydraulic leveraged dynamic anti-resonance vibration isolator with nonlinear damping characteristics." Journal of Vibration and Control, February 8, 2022, 107754632110608. http://dx.doi.org/10.1177/10775463211060895.
Abstract:
The hydraulic leveraged dynamic anti-resonance vibration isolator with nonlinear damping characteristics are analyzed under harmonic excitations. A nonlinear mathematical model is proposed considering both the nonlinear damping of the fluid resistance and the volumetric stiffness induced by the bulge effect. The harmonic balance method, combined with the arc-length continuation algorithm, is performed to investigate the steady-state response and vibration transmissibility quantitively. The optimization of isolator parameters are obtained using the fixed-point theory, which leads to the relation between the damping coefficients and isolation performance. Parametric studies are then carried out to investigate the effects of the volumetric stiffness, bellows stiffness, and lever ratio on the isolation performance. The results indicate the importance of the damping parameters on the design of the band-stop characteristics to achieve the anticipated performance of anti-resonance isolators. Furthermore, the inertia-amplification ratio of the anti-resonance isolator needs to be balanced against its stopband suppression performance for the fluid-type leveraged system.
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Kono, Anna, Yu Shikano, Kenji F. Tanaka, Katsunori Yamaura, and Iku Tsutsui‐Kimura. "Inhibition of the dorsomedial striatal direct pathway is essential for the execution of action sequences." Neuropsychopharmacology Reports, August 8, 2023. http://dx.doi.org/10.1002/npr2.12369.
Abstract:
AbstractContrary to the previous notion that the dorsomedial striatum (DMS) is crucial for acquiring new learning, accumulated evidence has suggested that the DMS also plays a role in the execution of already learned action sequences. Here, we examined how the direct and indirect pathways in the DMS regulate action sequences using a task that requires animals to press a lever consecutively. Cell‐type‐specific bulk Ca2+ recording revealed that the direct pathway was inhibited at the time of sequence execution. The sequence‐related response was blunted in trials where the sequential behaviors were disrupted. Optogenetic activation at the sequence start caused distraction of action sequences without affecting motor function or memory of the task structure. By contrast with the direct pathway, the indirect pathway was slightly activated at the start of the sequence, but the optogenetic suppression of such sequence‐related signaling did not impact the behaviors. These results suggest that the inhibition of the DMS direct pathway promotes sequence execution potentially by suppressing the formation of a new association.
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Fernandez-Leon, Jose A., Douglas S. Engelke, Guillermo Aquino-Miranda, Alexandria Goodson, Maria N. Rasheed, and Fabricio H. Do Monte. "Neural correlates and determinants of approach–avoidance conflict in the prelimbic prefrontal cortex." eLife 10 (December 16, 2021). http://dx.doi.org/10.7554/elife.74950.
Abstract:
The recollection of environmental cues associated with threat or reward allows animals to select the most appropriate behavioral responses. Neurons in the prelimbic (PL) cortex respond to both threat- and reward-associated cues. However, it remains unknown whether PL regulates threat-avoidance vs. reward-approaching responses when an animals’ decision depends on previously associated memories. Using a conflict model in which male Long–Evans rats retrieve memories of shock- and food-paired cues, we observed two distinct phenotypes during conflict: (1) rats that continued to press a lever for food (Pressers) and (2) rats that exhibited a complete suppression in food seeking (Non-pressers). Single-unit recordings revealed that increased risk-taking behavior in Pressers is associated with persistent food-cue responses in PL, and reduced spontaneous activity in PL glutamatergic (PLGLUT) neurons during conflict. Activating PLGLUT neurons in Pressers attenuated food-seeking responses in a neutral context, whereas inhibiting PLGLUT neurons in Non-pressers reduced defensive responses and increased food approaching during conflict. Our results establish a causal role for PLGLUT neurons in mediating individual variability in memory-based risky decision-making by regulating threat-avoidance vs. reward-approach behaviors.
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Simon, Lena, Thierry Langin, Benjamin Nowak, and Gaëlle Marliac. "Perennial soil characteristics are the main factor driving in vitro inhibition of the wheat fungal pathogen Fusarium graminearum in a French case study." Soil Use and Management, November 27, 2023. http://dx.doi.org/10.1111/sum.12998.
Abstract:
AbstractSoils are termed “suppressive” when they can limit the emergence and propagation of plant diseases. However, little is known regarding what factors determine suppressiveness and whether they could be improved for a given soil. Agricultural practices, such as tillage systems, influence the properties of the soil, and could be a lever to improve soil suppression of pathogens.In this study, we investigated the impact of soil type and crop management practices on soil suppressiveness towards Fusarium graminearum, a major winter wheat (Triticum aestivum) pathogen. As it is transmitted via crop residues left on soil, F. graminearum is susceptible to soil suppression.Soil suppressiveness has been evaluated in more than a hundred sampled fields in the Limagne plain (Puy‐de‐Dôme, France), to represent a great diversity of soil types (either calcisol, vertisol or fluvisol) and cropping systems (organic, reduced tillage or intensive cropping systems). The physicochemical composition of the sampled soils and crop management practices, identified through farmer surveys, were included in a generalized linear mixed‐effect model to explain soil fungistasis.A fungistasis test was performed by putting a plug of PDA‐agar inoculated with Fusarium in contact with the soil and measuring the area of fungal growth. This test revealed a wide variety of soil fungistatic properties, ranging from conducive soils (22% of soil covered by fungal growth) to very suppressive soils (1% of soil covered). Suppressiveness was related to soil perennial properties (p‐value < 0.001) rather than practices.Overall, these results show that soil type and composition play a key role in fungistasis, and that soil suppressiveness is a complex, multifactorial process.
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Bryant, Kathleen G., Mitchell A. Nothem, Lauren A. Buck, Binay Singh, Sana Amin, Christina M. Curran-Alfaro, and Jacqueline M. Barker. "A history of low-dose ethanol shifts the role of ventral hippocampus during reward seeking in male mice." eneuro, May 8, 2023, ENEURO.0087–23.2023. http://dx.doi.org/10.1523/eneuro.0087-23.2023.
Abstract:
Although casual drinkers are a majority of the alcohol drinking population, understanding of the long-term effects of chronic exposure to lower levels of alcohol is limited. Chronic exposure to lower doses of ethanol may facilitate the development of alcohol use disorders, potentially due to ethanol effects on reward learning and motivation. Indeed, our previously published findings showed that chronic low-dose ethanol exposure enhanced motivation for sucrose in male, but not female, mice. As the ventral hippocampus (vHPC) is sensitive to disruption by higher doses of chronic ethanol and tracks reward-related information, we hypothesized that this region is impacted by low-dose ethanol and, further, that manipulating vHPC activity would alter reward motivation.In vivoelectrophysiological recordings of vHPC population neural activity during progressive ratio testing revealed that vHPC activity was suppressed in the period immediately after reward seeking (lever press) in ethanol-naïve controls, whereas suppression of vHPC activity anticipated reward seeking in ethanol-exposed mice. In both ethanol-naïve and exposed mice, vHPC activity was suppressed prior to a reward magazine entry. Temporally selective inhibition of vHPC using optogenetics increased motivation for sucrose in ethanol-naïve controls, but not in ethanol-exposed mice. Further, regardless of exposure history, vHPC inhibition promoted checking of the reward magazine, indicating a role for vHPC in reward tracking. There was no effect of chemogenetic inhibition of the vHPC either during training or testing on sucrose reward motivation. These results reveal novel ethanol-induced alterations in vHPC neural activity that shift how vHPC activity is able to regulate reward seeking.Significance StatementA large portion of the population consumes alcohol at levels that are subthreshold for an alcohol use disorder. Low-dose ethanol exposure could help convey susceptibility to alcohol use disorders by disrupting activity in brain regions that are important in reward seeking and motivation like the ventral hippocampus. Here, we found that a history of low-dose ethanol exposure shifted ventral hippocampus encoding of actions in mice, such that it altered the role of ventral hippocampus in reward seeking. These findings further our understanding of the impacts of low-dose ethanol exposure on motivated behavior and reveal ethanol-induced modulations in neural correlates of reward motivation.