Chronic-moderate ethanol exposure of L(tk-) cells expressing ? 4? 3? GABAA receptors reduces potency of allopregnanolone potentiation of GABA-evoked inward currents: Possible role of PKC

Aim: To investigate the effect of chronic-moderate ethanol (CME) treatment upon direct activation and allosteric modulation of GABAA receptors, and to assess the sensitivity of these parameters to PKC inhibition in control and ethanol-treated cells. Methods: L(tk-) cells were exposed to 20mM ethanol in culture media for 14 days prior to induction of stable expression of human recombinant ?4?3? receptors using dexamethasone. Concentration-response curves for GABA (1nM - 100µM), and allopregnanolone (ALLO; 1nM - 30µM) co-applied with 200nM GABA were obtained using whole-cell patch-clamp electrophysiology at a holding voltage of -60 mV. 400nM calphostin C (CphC) or vehicle (DMSO) was administered to cells via the pipette solution, which was prepared with 2mM Mg.ATP. SDS-PAGE and western blotting were used to compare levels of whole-cell expression, quantified relative to ?-actin, of ?4 and ? GABAA receptor subunits, and several isoforms of PKC (?, ?, ?, and ?), in control and CME-treated cells. Data was reported as Mean ± SEM and significance determined by either one-way ANOVA with Newman-Keuls multiple comparison tests, or two-way, unpaired t-tests. Results: Expression of ?4 subunits was reduced 35% (P0.05) and pEC50 (control: 6.18±0.04, n=13, CME: 6.17±0.04, n=4, P>0.05) of GABA were unchanged. CphC increased the GABA pEC50 relative to control (6.62±0.08, n=3, P<0.001) but had no effect upon responses at pEC20 GABA. Following CME, the potency of GABA was unaltered in the presence of CphC. The magnitude of ALLO-induced potentiation in control cells (7.34±0.6 fold, n=19) was unchanged by CME (ATP: 7.39±1.0 fold, n=9, P>0.05), and CphC had no significant effect in control or CME-treated cells. The ALLO pEC50 in control cells (6.23±0.05, n=19) was unaffected by CphC. Following CME, the potency of ALLO was reduced (5.68±0.06, n=9, P<0.001) but was enhanced in the presence of CphC, which restored potency almost back to control levels (5.94±0.09, n=5, P<0.05 relative to control). Expression of the ?, ?, ?, and ? isoforms of PKC was detected in whole-cell lysates of L(tk-) cells but only PKC? was significantly altered by CME treatment, exhibiting a nearly 4-fold increase (3.9±0.47 fold P<0.01) when compared with that in controls. Discussion: CME of un-induced L(tk-) cells was sufficient to alter sensitivity of ?4?3? receptor function to alterations of the balance of phosphorylation induced by CphC. The increased expression of PKC? after CME may have been directly related to the absence of effect of CphC upon GABA potency. As direct interaction of GABAA receptors with PKC? has not been determined, the effects observed for potency and efficacy of ALLO following CME may be indicative of changes to the phosphorylation of accessory proteins or other PKC isoforms by PKC?

Reviews

Computers and Typography edited by Rosemary Sassoon, Oxford, Intellect, 1993. ISBN: 1–871516–23–4

Heavy Quarks and Heavy Quarkonia as Tests of Thermalization

We present here a brief summary of new results on heavy quarks and heavy quarkonia from the PHENIX experiment as presented at the "Quark Gluon Plasma Thermalization" Workshop in Vienna, Austria in August 2005, directly following the International Quark Matter Conference in Hungary.Comment: 8 pages, 5 figures, Quark Gluon Plasma Thermalization Workshop (Vienna August 2005) Proceeding

Velocity-space sensitivity of the time-of-flight neutron spectrometer at JET

The velocity-space sensitivities of fast-ion diagnostics are often described by so-called weight functions. Recently, we formulated weight functions showing the velocity-space sensitivity of the often dominant beam-target part of neutron energy spectra. These weight functions for neutron emission spectrometry (NES) are independent of the particular NES diagnostic. Here we apply these NES weight functions to the time-of-flight spectrometer TOFOR at JET. By taking the instrumental response function of TOFOR into account, we calculate time-of-flight NES weight functions that enable us to directly determine the velocity-space sensitivity of a given part of a measured time-of-flight spectrum from TOFOR

On the mechanisms governing gas penetration into a tokamak plasma during a massive gas injection

A new 1D radial fluid code, IMAGINE, is used to simulate the penetration of gas into a tokamak plasma during a massive gas injection (MGI). The main result is that the gas is in general strongly braked as it reaches the plasma, due to mechanisms related to charge exchange and (to a smaller extent) recombination. As a result, only a fraction of the gas penetrates into the plasma. Also, a shock wave is created in the gas which propagates away from the plasma, braking and compressing the incoming gas. Simulation results are quantitatively consistent, at least in terms of orders of magnitude, with experimental data for a D 2 MGI into a JET Ohmic plasma. Simulations of MGI into the background plasma surrounding a runaway electron beam show that if the background electron density is too high, the gas may not penetrate, suggesting a possible explanation for the recent results of Reux et al in JET (2015 Nucl. Fusion 55 093013)

Consequences of various landscape-scale ecosystem management strategies and fire cycles on age-class structure and harvest in boreal forests

At the landscape scale, one of the key indicators of sustainable forest management is the age-class distribution of stands, since it provides a coarse synopsis of habitat potential, structural complexity, and stand volume, and it is directly modified by timber extraction and wildfire. To explore the consequences of several landscape-scale boreal forest management strategies on age-class structure in the Mauricie region of Quebec, we used spatially explicit simulation modelling. Our study investigated three different harvesting strategies (the one currently practiced and two different strategies to maintain late seral stands) and interactions between fire and harvesting on stand age-class distribution. We found that the legacy of initial forested age structure and its spatial configuration can pose short- (<50 years) to medium-term (150-300 years) challenges to balancing wood supply and ecological objectives. Also, ongoing disturbance by fire, even at relatively long cycles in relation to historic levels, can further constrain the achievement of both timber and biodiversity goals. For example, when fire was combined with management, harvest shortfalls occurred in all scenarios with a fire cycle of 100 years and most scenarios with a fire cycle of 150 years. Even a fire cycle of 500 years led to a reduction in older forest when its maintenance was not a primary constraint. Our results highlight the need to consider the broad-scale effects of natural disturbance when developing ecosystem management policies and the importance of prioritizing objectives when planning for multiple resource use

Percolating granular superconductors

We investigate diamagnetic fluctuations in percolating granular superconductors. Granular superconductors are known to have a rich phase diagram including normal, superconducting and spin glass phases. Focusing on the normal-superconducting and the normal-spin glass transition at low temperatures, we study he diamagnetic susceptibility $\chi^{(1)}$ and the mean square fluctuations of the total magnetic moment $\chi^{(2)}$ of large clusters. Our work is based on a random Josephson network model that we analyze with the powerful methods of renormalized field theory. We investigate the structural properties of the Feynman diagrams contributing to the renormalization of $\chi^{(1)}$ and $\chi^{(2)}$. This allows us to determine the critical behavior of $\chi^{(1)}$ and $\chi^{(2)}$ to arbitrary order in perturbation theory.Comment: 18 pages, 2 figure

Relationship of edge localized mode burst times with divertor flux loop signal phase in JET

A phase relationship is identified between sequential edge localized modes (ELMs) occurrence times in a set of H-mode tokamak plasmas to the voltage measured in full flux azimuthal loops in the divertor region. We focus on plasmas in the Joint European Torus where a steady H-mode is sustained over several seconds, during which ELMs are observed in the Be II emission at the divertor. The ELMs analysed arise from intrinsic ELMing, in that there is no deliberate intent to control the ELMing process by external means. We use ELM timings derived from the Be II signal to perform direct time domain analysis of the full flux loop VLD2 and VLD3 signals, which provide a high cadence global measurement proportional to the voltage induced by changes in poloidal magnetic flux. Specifically, we examine how the time interval between pairs of successive ELMs is linked to the time-evolving phase of the full flux loop signals. Each ELM produces a clear early pulse in the full flux loop signals, whose peak time is used to condition our analysis. The arrival time of the following ELM, relative to this pulse, is found to fall into one of two categories: (i) prompt ELMs, which are directly paced by the initial response seen in the flux loop signals; and (ii) all other ELMs, which occur after the initial response of the full flux loop signals has decayed in amplitude. The times at which ELMs in category (ii) occur, relative to the first ELM of the pair, are clustered at times when the instantaneous phase of the full flux loop signal is close to its value at the time of the first ELM

A multi-country test of brief reappraisal interventions on emotions during the COVID-19 pandemic

The COVID-19 pandemic has increased negative emotions and decreased positive emotions globally. Left unchecked, these emotional changes might have a wide array of adverse impacts. To reduce negative emotions and increase positive emotions, we tested the effectiveness of reappraisal, an emotion-regulation strategy that modifies how one thinks about a situation. Participants from 87 countries and regions (n = 21,644) were randomly assigned to one of two brief reappraisal interventions (reconstrual or repurposing) or one of two control conditions (active or passive). Results revealed that both reappraisal interventions (vesus both control conditions) consistently reduced negative emotions and increased positive emotions across different measures. Reconstrual and repurposing interventions had similar effects. Importantly, planned exploratory analyses indicated that reappraisal interventions did not reduce intentions to practice preventive health behaviours. The findings demonstrate the viability of creating scalable, low-cost interventions for use around the world