Allosteric interactions of gaba- and glycine-gated chloride channels from rat brain.

The allosteric interactions of the GABAA receptor were investigated through the actions of drugs on [3H]-flunitrazepam binding. The effects of varying incubation temperature revealed that pentobarbitone is more efficacious a potentiator at low temperatures than at high. In contrast, the general anaesthetics propofol and alphaxalone did not show a variation in efficacy with temperature. These results argue against a membrane site of action for propofol and alphaxalone. Differences in the dependence of potentiation upon anions were also noted. All three drugs gave increased potentiation with increasing concentrations of anions which can permeate the GABAA receptor. However, whilst the potency of propofol increased with chloride concentration, its efficacy did not. Pentobarbitone showed an increase in both potency and efficacy but whilst alphaxalone's efficacy increased, its potency did not. These results indicate different sites and modes of interaction for propofol, alphaxalone and pentobarbitone. Interactions of the steroid epipregnanolone with the receptor were also characterised. It antagonised competitively the potentiation produced by its isomers pregnanolone and allopregnanolone whilst having little direct effect upon flunitrazepam binding or on potentiation by pentobarbitone and GABA. Epipregnanolone also antagonized the potentiating effect of alphaxalone but the mode of inhibition was different to that seen against pregnanolone, indicating more than one class of binding site for neurosteroids at the GABAA receptor. [3H]-flunitrazepam binding to GABAA receptors immunopurified according to a subunit content was also examined. No potentiation by alphaxalone or pentobarbitone was seen but differences in flunitrazepam affinity and EC50 for potentiation by GABA were noted. In an electrophysiological study, the interaction of steroids with the strychnine-sensitive glycine receptor was examined. Certain corticosteroids were shown to be potent enhancers of the actions of glycine and strychnine at this receptor, but steroids which are active on the GABAA receptor showed no effects

Research in cosmic and gamma ray astrophysics

Discussed here is research in cosmic ray and gamma ray astrophysics at the Space Radiation Laboratory (SRL) of the California Institute of Technology. The primary activities discussed involve the development of new instrumentation and techniques for future space flight. In many cases these instrumentation developments were tested in balloon flight instruments designed to conduct new investigations in cosmic ray and gamma ray astrophysics. The results of these investigations are briefly summarized. Specific topics include a quantitative investigation of the solar modulation of cosmic ray protons and helium nuclei, a study of cosmic ray positron and electron spectra in interplanetary and interstellar space, the solar modulation of cosmic rays, an investigation of techniques for the measurement and interpretation of cosmic ray isotopic abundances, and a balloon measurement of the isotopic composition of galactic cosmic ray boron, carbon, and nitrogen

Of the Necessity of a Censorship of the Press, 1808

2 pages, correspondenceMetternich argues to Count Stadion that, in order to effectively thwart revolutionary activity, the government must censor the press (1808)

A ship in harbour is safe, but that is not what ships are built for: an overview of outdoor studies at St Martin's College

Sea-going vessels come in all shapes and sizes with different hulls and rigging. Different people view them through different eyes. The vessel that is Outdoor Studies at St Martinʼs College is one of those well-loved craft of indeterminate class that has been so constantly trimmed and re-fitted, it isnʼt the vessel it was. However it handles well in most conditions and the crews pass through happily enough. The keel was laid over thirty years ago by Colin Mortlock, and was designed for small crews and high performance, an Advanced Certificate in Adventure Education. She sailed far and wide and the crews weathered well, sailing demanding courses under a strong navigator. The strengths of this approach were soon recognised and offers came to add a new dimension to Initial Teacher Training at Charlotte Mason College, developing in student teachers those characteristics that constitute a well-rounded crewmember

Mechanism of Tacrine Block at Adult Human Muscle Nicotinic Acetylcholine Receptors

We used single-channel kinetic analysis to study the inhibitory effects of tacrine on human adult nicotinic receptors (nAChRs) transiently expressed in HEK 293 cells. Single channel recording from cell-attached patches revealed concentration- and voltage-dependent decreases in mean channel open probability produced by tacrine (IC50 4.6 μM at −70 mV, 1.6 μM at −150 mV). Two main effects of tacrine were apparent in the open- and closed-time distributions. First, the mean channel open time decreased with increasing tacrine concentration in a voltage-dependent manner, strongly suggesting that tacrine acts as an open-channel blocker. Second, tacrine produced a new class of closings whose duration increased with increasing tacrine concentration. Concentration dependence of closed-times is not predicted by sequential models of channel block, suggesting that tacrine blocks the nAChR by an unusual mechanism. To probe tacrine's mechanism of action we fitted a series of kinetic models to our data using maximum likelihood techniques. Models incorporating two tacrine binding sites in the open receptor channel gave dramatically improved fits to our data compared with the classic sequential model, which contains one site. Improved fits relative to the sequential model were also obtained with schemes incorporating a binding site in the closed channel, but only if it is assumed that the channel cannot gate with tacrine bound. Overall, the best description of our data was obtained with a model that combined two binding sites in the open channel with a single site in the closed state of the receptor

COMPLETED RESEARCH: PRELIMINARY INSIGHTS INTO THE IMPACT OF DIGITAL PLATFORMS FOR MUSIC

In this study, we investigated the perception of a musician who sells his music on a digital platform in Ghana. We specifically examined the motivations for choosing that digital platform, the benefits being derived, and what could make him stop using that platform. We adopted a qualitative research approach and conducted in-depth interviews with the musician, and the owner of our target digital platform, Aftown.com. We found that the digital platform extends a musician’s reach to an audience beyond her geographical boundary, generates increased sales, and removes intermediaries between her and the customer. Digital platforms, especially a local one also helps overcome digital payment constraints because it is equipped with solutions like mobile money that enables local purchases, and not restricted to just popular international payment systems. The originality of this study lies in the fact that, it is one of the few scholarly investigations focusing on digital platforms from of a sub-Saharan country perspective

The Influence of Religion on Capital Structure Decision among Small and Medium Enterprises in Ghana

This paper examines the influence of religion on capital structure decisions of small and medium enterprises (SMEs) in Ghana. The issue is very relevant considering the meritorious contributions SMEs offer to growth of the Ghanaian economy. Exploratory- descriptive of its kind, this study adopts quantitative and quota sampling approaches to select 200 SMEs owned and manage being Christians and Moslems. Statistically, the results of the study suggest that religion has a significantly weak influence as far as decisions on capital structure are concern. The direction of the study revealed that relative to Muslims, SME operators being Christians greatly accounted to the significant influence religion had on total capital structure of SME businesses. Since most SMEs owners value full ownership of their business, any capital structure that risk their full control may not be entertain. Keywords: Capital Structure, Religion, Small and medium enterprise (SME

Autonomous Aerobraking: A Design, Development, and Feasibility Study

Aerobraking has been used four times to decrease the apoapsis of a spacecraft in a captured orbit around a planetary body with a significant atmosphere utilizing atmospheric drag to decelerate the spacecraft. While aerobraking requires minimum fuel, the long time required for aerobraking requires both a large operations staff, and large Deep Space Network resources. A study to automate aerobraking has been sponsored by the NASA Engineering and Safety Center to determine initial feasibility of equipping a spacecraft with the onboard capability for autonomous aerobraking, thus saving millions of dollars incurred by a large aerobraking operations workforce and continuous DSN coverage. This paper describes the need for autonomous aerobraking, the development of the Autonomous Aerobraking Development Software that includes an ephemeris estimator, an atmospheric density estimator, and maneuver calculation, and the plan forward for continuation of this study

Comparisons Of Proctored Versus Non-Proctored Testing Strategies In Graduate Distance Education Curriculum

The authors studied the testing pattern grades in four e-campus courses at Troy University with 76 graduate students. In their research, the authors found significant differences in average test grade scores between tests taken electronically without a proctor as compared to those administered using a live or a remote proctor overall. To control for differences among courses, a statistical test was solely conducted on the courses which had the same instructor, same text, and similar tests with comparable results; students scored significantly lower on proctored exams versus non-proctored exams. To enhance the quality of courses in the online environment, the researchers recommend several “best practices” pedagogical strategies based on their findings and an extensive literature review