780 research outputs found

    Electrophysiological characterization of activation state-dependent Cav2 channel antagonist TROX-1 in spinal nerve injured rats

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    AbstractPrialt, a synthetic version of Cav2.2 antagonist ω-conotoxin MVIIA derived from Conus magus, is the first clinically approved voltage-gated calcium channel blocker for refractory chronic pain. However, due to the narrow therapeutic window and considerable side effects associated with systemic dosing, Prialt is only administered intrathecally. N-triazole oxindole (TROX-1) is a novel use-dependent and activation state-selective small-molecule inhibitor of Cav2.1, 2.2 and 2.3 calcium channels designed to overcome the limitations of Prialt. We have examined the neurophysiological and behavioral effects of blocking calcium channels with TROX-1. In vitro, TROX-1, in contrast to state-independent antagonist Prialt, preferentially inhibits Cav2.2 currents in rat dorsal root ganglia (DRG) neurons under depolarized conditions. In vivo electrophysiology was performed to record from deep dorsal horn lamina V/VI wide dynamic range neurons in non-sentient spinal nerve-ligated (SNL) and sham-operated rats. In SNL rats, spinal neurons exhibited reduced responses to innocuous and noxious punctate mechanical stimulation of the receptive field following subcutaneous administration of TROX-1, an effect that was absent in sham-operated animals. No effect was observed on neuronal responses evoked by dynamic brushing, heat or cold stimulation in SNL or sham rats. The wind-up response of spinal neurons following repeated electrical stimulation of the receptive field was also unaffected. Spinally applied TROX-1 dose dependently inhibited mechanically evoked neuronal responses in SNL but not sham-operated rats, consistent with behavioral observations. This study confirms the pathological state-dependent actions of TROX-1 through a likely spinal mechanism and reveals a modality selective change in calcium channel function following nerve injury

    Bounds on the basic physical parameters for anisotropic compact general relativistic objects

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    We derive upper and lower limits for the basic physical parameters (mass-radius ratio, anisotropy, redshift and total energy) for arbitrary anisotropic general relativistic matter distributions in the presence of a cosmological constant. The values of these quantities are strongly dependent on the value of the anisotropy parameter (the difference between the tangential and radial pressure) at the surface of the star. In the presence of the cosmological constant, a minimum mass configuration with given anisotropy does exist. Anisotropic compact stellar type objects can be much more compact than the isotropic ones, and their radii may be close to their corresponding Schwarzschild radii. Upper bounds for the anisotropy parameter are also obtained from the analysis of the curvature invariants. General restrictions for the redshift and the total energy (including the gravitational contribution) for anisotropic stars are obtained in terms of the anisotropy parameter. Values of the surface redshift parameter greater than two could be the main observational signature for anisotropic stellar type objects.Comment: 18 pages, no figures, accepted for publication in CQ

    In-Class Versus At-Home Quizzes: Which is Better? A Flipped Learning Study in a Two-Site Synchronously-Broadcast Organic Chemistry Course

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    We recently shared our design of a two-semester flipped organic chemistry course, in which we gave students in-class quizzes to incentivize attendance and watching the lecture videos in advance. With a second iteration, we planned to make the video-watching experience more engaging. We accordingly hypothesized that if students completed short at-home quizzes while watching the videos, then attentiveness, engagement, and learning would increase. We tested this with a later section of the course, dividing the material into 13 units. For units 1-6, we gave in-class quizzes; for 7-13, quizzes were at home. Although units 1-6 and 7-13 covered different material, we were nonetheless surprised when students’ average quiz scores decreased for the take-home quizzes, because they did not have a time limit and were open-book, unlike the in-class quizzes. Anonymous survey feedback showed a strong preference for quizzes in class and indications that take-home quizzes demotivated attendance and pre-class watching of the videos. Thus, for analogous flipped course designs in chemistry, we recommend an in-class quizzing strategy over take-home quizzes to positively affect engagement, learning, and attendance. Of note, this course was synchronously delivered to two groups of students at geographically-distinct satellite locations

    Effect of temperature anisotropy on various modes and instabilities for a magnetized non-relativistic bi-Maxwellian plasma

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    Using kinetic theory for homogeneous collisionless magnetized plasmas, we present an extended review of the plasma waves and instabilities and discuss the anisotropic response of generalized relativistic dielectric tensor and Onsager symmetry properties for arbitrary distribution functions. In general, we observe that for such plasmas only those electromagnetic modes whose magnetic field perturbations are perpendicular to the ambient magneticeld, i.e.,B1 \perp B0, are effected by the anisotropy. However, in oblique propagation all modes do show such anisotropic effects. Considering the non-relativistic bi-Maxwellian distribution and studying the relevant components of the general dielectric tensor under appropriate conditions, we derive the dispersion relations for various modes and instabilities. We show that only the electromagnetic R- and L- waves, those derived from them and the O-mode are affected by thermal anisotropies, since they satisfy the required condition B1\perpB0. By contrast, the perpendicularly propagating X-mode and the modes derived from it (the pure transverse X-mode and Bernstein mode) show no such effect. In general, we note that the thermal anisotropy modifies the parallel propagating modes via the parallel acoustic effect, while it modifies the perpendicular propagating modes via the Larmor-radius effect. In oblique propagation for kinetic Alfven waves, the thermal anisotropy affects the kinetic regime more than it affects the inertial regime. The generalized fast mode exhibits two distinct acoustic effects, one in the direction parallel to the ambient magnetic field and the other in the direction perpendicular to it. In the fast-mode instability, the magneto-sonic wave causes suppression of the firehose instability. We discuss all these propagation characteristics and present graphic illustrations

    Self-Regulation in a Web-Based Course: A Case Study

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    Little is known about how successful students in Web-based courses self-regulate their learning. This descriptive case study used a social cognitive model of self-regulated learning (SRL) to investigate how six graduate students used and adapted traditional SRL strategies to complete tasks and cope with challenges in a Web-based technology course; it also explored motivational and environmental influences on strategy use. Primary data sources were three transcribed interviews with each of the students over the course of the semester, a transcribed interview with the course instructor, and the students’ reflective journals. Archived course documents, including transcripts of threaded discussions and student Web pages, were secondary data sources. Content analysis of the data indicated that these students used many traditional SRL strategies, but they also adapted planning, organization, environmental structuring, help seeking, monitoring, record keeping, and self-reflection strategies in ways that were unique to the Web-based learning environment. The data also suggested that important motivational influences on SRL strategy use—self-efficacy, goal orientation, interest, and attributions—were shaped largely by student successes in managing the technical and social environment of the course. Important environmental influences on SRL strategy use included instructor support, peer support, and course design. Implications for online course instructors and designers, and suggestions for future research are offered

    Modeling Polar Cap \u3ci\u3eF\u3c/i\u3e-Region Patches Using Time Varying Convection

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    Creation of polar cap F‐region patches are simulated for the first time using two independent physical models of the high latitude ionosphere. The patch formation is achieved by temporally varying the magnetospheric electric field (ionospheric convection) input to the models. The imposed convection variations are comparable to changes in the convection that result from changes in the By IMF component for southward interplanetary magnetic field (IMF). Solar maximum‐winter simulations show that simple changes in the convection pattern lead to significant changes in the polar cap plasma structuring. Specifically, in winter, as enhanced dayside plasma convects into the polar cap to form the classic tongue‐of‐ionization (TOI) the convection changes produce density structures that are indistinguishable from the observed patches
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