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

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

A self‐consistent model of helium in the thermosphere

We have found that consideration of neutral helium as a major species leads to a more complete physics‐based modeling description of the Earth's upper thermosphere. An augmented version of the composition equation employed by the Thermosphere‐Ionosphere‐Electrodynamic General Circulation Model (TIE‐GCM) is presented, enabling the inclusion of helium as the fourth major neutral constituent. Exospheric transport acting above the upper boundary of the model is considered, further improving the local time and latitudinal distributions of helium. The new model successfully simulates a previously observed phenomenon known as the “winter helium bulge,” yielding behavior very similar to that of an empirical model based on mass spectrometer observations. This inclusion has direct consequence on the study of atmospheric drag for low‐Earth‐orbiting satellites, as well as potential implications on exospheric and topside ionospheric research.Key PointsTIE‐GCM has been modified to account for neutral heliumSeasonal behavior is successfully capturedNeutral densities from the new model agree well with previous observationsPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/113723/1/jgra51979.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/113723/2/jgra51979_am.pd

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

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

Platinum Group Metal-Doped Tungsten Phosphates for Selective C-H Activation of Lower Alkanes

Platinum group metal (PGM)-based catalysts are known to be highly active in the total combustion of lower hydrocarbons. However, through an alternative catalyst design reported in this paper by isolating PGM-based active sites in a tungsten phosphate matrix, we present a class of catalysts for selective oxidation of n-butane, propane, and propylene that do not contain Mo or V as redox-active elements. Two different catalyst concepts have been pursued. Concept A: isolating Ru-based active sites in a tungsten phosphate matrix coming upon as ReO3-type structure. Concept B: dilution of PGM-based active sites through the synthesis of X-ray amorphous Ru tungsten phosphates supported on SiO2. Using a high-throughput screening approach, model catalysts over a wide compositional range were evaluated for C3 and C4 partial oxidation. Bulk crystalline and supported XRD amorphous phases with similar Ru/W/P compositions showed comparable performance. Hence, for these materials, composition is more crucial than the degree of crystallinity. Further studies for optimization on second-generation supported systems revealed even better results. High selectivity for n-butane oxidation to maleic anhydride and propane oxidation to an acrolein/acrylic acid has been achieved

The role of self-efficacy as an attribute of principals’ leadership effectiveness in K-12 private and public institutions in Lebanon

© 2018, © 2018 Informa UK Limited, trading as Taylor & Francis Group. The aim of this study is to explore the role of K-12 school principals’ self-efficacy as an attribute for their leadership effectiveness in Lebanon. The Norwegian principal self-efficacy scale (NPSES) instrument was translated into Arabic and used to collect quantitative data from participants. Internal consistency of factors within this study was checked (24 items; α = 0.73). By comparing private and public schools in Lebanon, all located in the governorate of Mount Lebanon, the researchers revealed the extent to which principals’ self-efficacy plays a role in their leadership. In addition, while no statistical difference was found between self-efficacy levels of private and public principals, females reported higher scores on the majority of the dimensions than their male counterparts in both types of schools. This study highlights the importance of the interaction effect of age and gender on self-efficacy levels. Moreover, it offers knowledge and practice to policy makers when recruiting principals or designing training programs. It also suggests the implementation of an in-house mentoring program to create school-school partnerships. Finally, this paper offers a platform for future researchers interested in principal self-efficacy in similar conflict-affected places with high economic depression. Limitations are further mentioned

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

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

Estimation of cold plasma outflow during geomagnetic storms

Low-energy ions of ionospheric origin constitute a significant contributor to the magnetospheric plasma population. Measuring cold ions is difficult though. Observations have to be done at sufficiently high altitudes and typically in regions of space where spacecraft attain a positive charge due to solar illumination. Cold ions are therefore shielded from the satellite particle detectors. Furthermore, spacecraft can only cover key regions of ion outflow during segments of their orbit, so additional complications arise if continuous longtime observations, such as during a geomagnetic storm, are needed. In this paper we suggest a new approach, based on a combination of synoptic observations and a novel technique to estimate the flux and total outflow during the various phases of geomagnetic storms. Our results indicate large variations in both outflow rates and transport throughout the storm. Prior to the storm main phase, outflow rates are moderate, and the cold ions are mainly emanating from moderately sized polar cap regions. Throughout the main phase of the storm, outflow rates increase and the polar cap source regions expand. Furthermore, faster transport, resulting from enhanced convection, leads to a much larger supply of cold ions to the near-Earth region during geomagnetic storms. ©2015. The Authors

Micro-Ethical Decision Making Among Baccalaureate Nursing Students: A Qualitative Investigation

Nursing students frequently encounter micro-ethical nursing practice problems during their clinical experience. The purpose of this study was to understand the lived experiences of senior-level baccalaureate students faced with making micro-ethical clinical decisions in practice settings. A descriptive qualitative design was used, and five central themes emerged. A dominant finding was the experience of unapplied and forgotten ethics education revealing a mismatch between what faculty perceived was taught and students’ experiences of that education. When faced with micro-ethical decisions, participants trusted and deferred to staff nurse recommendations, even if the advice contradicted best-practice standards. Contextual naivete was brought out of concealment, contributing to the experience of moral disequilibrium (i.e., students felt conflicted about what they learned in school as best practice and what they observed being role modeled in the clinical environment). This study resulted in theory-guided implications for nursing education and recommendations for future study