Phosphorylation of the voltage-gated potassium channel Kv2.1 by AMP-activated protein kinase regulates membrane excitability

Firing of action potentials in excitable cells accelerates ATP turnover. The voltage-gated potassium channel Kv2.1 regulates action potential frequency in central neurons, whereas the ubiquitous cellular energy sensor AMP-activated protein kinase (AMPK) is activated by ATP depletion and protects cells by switching off energy-consuming processes. We show that treatment of HEK293 cells expressing Kv2.1 with the AMPK activator A-769662 caused hyperpolarizing shifts in the current-voltage relationship for channel activation and inactivation. We identified two sites (S440 and S537) directly phosphorylated on Kv2.1 by AMPK and, using phosphospecific antibodies and quantitative mass spectrometry, show that phosphorylation of both sites increased in A-769662-treated cells. Effects of A-769662 were abolished in cells expressing Kv2.1 with S440A but not with S537A substitutions, suggesting that phosphorylation of S440 was responsible for these effects. Identical shifts in voltage gating were observed after introducing into cells, via the patch pipette, recombinant AMPK rendered active but phosphatase-resistant by thiophosphorylation. Ionomycin caused changes in Kv2.1 gating very similar to those caused by A-769662 but acted via a different mechanism involving Kv2.1 dephosphorylation. In cultured rat hippocampal neurons, A-769662 caused hyperpolarizing shifts in voltage gating similar to those in HEK293 cells, effects that were abolished by intracellular dialysis with Kv2.1 antibodies. When active thiophosphorylated AMPK was introduced into cultured neurons via the patch pipette, a progressive, time-dependent decrease in the frequency of evoked action potentials was observed. Our results suggest that activation of AMPK in neurons during conditions of metabolic stress exerts a protective role by reducing neuronal excitability and thus conserving energy.

Transient climate change simulations with a coupled atmosphere–ocean GCM including the tropospheric sulfur cycle

The time-dependent climate response to changing concentrations of greenhouse gases and sulfate aerosols is studied using a coupled general circulation model of the atmosphere and the ocean (ECHAM4/OPYC3). The concentrations of the well-mixed greenhouse gases like CO2, CH4, N2O, and CFCs are prescribed for the past (1860–1990) and projected into the future according to International Panel on Climate Change (IPCC) scenario IS92a. In addition, the space–time distribution of tropospheric ozone is prescribed, and the tropospheric sulfur cycle is calculated within the coupled model using sulfur emissions of the past and projected into the future (IS92a). The radiative impact of the aerosols is considered via both the direct and the indirect (i.e., through cloud albedo) effect. It is shown that the simulated trend in sulfate deposition since the end of the last century is broadly consistent with ice core measurements, and the calculated radiative forcings from preindustrial to present time are within the uncertainty range estimated by IPCC. Three climate perturbation experiments are performed, applying different forcing mechanisms, and the results are compared with those obtained from a 300-yr unforced control experiment. As in previous experiments, the climate response is similar, but weaker, if aerosol effects are included in addition to greenhouse gases. One notable difference to previous experiments is that the strength of the Indian summer monsoon is not fundamentally affected by the inclusion of aerosol effects. Although the monsoon is damped compared to a greenhouse gas only experiment, it is still more vigorous than in the control experiment. This different behavior, compared to previous studies, is the result of the different land–sea distribution of aerosol forcing. Somewhat unexpected, the intensity of the global hydrological cycle becomes weaker in a warmer climate if both direct and indirect aerosol effects are included in addition to the greenhouse gases. This can be related to anomalous net radiative cooling of the earth’s surface through aerosols, which is balanced by reduced turbulent transfer of both sensible and latent heat from the surface to the atmosphere.

Using paleo-climate comparisons to constrain future projections in CMIP5

We present a description of the theoretical framework and "best practice" for using the paleo-climate model component of the Coupled Model Intercomparison Project (Phase 5) (CMIP5) to constrain future projections of climate using the same models. The constraints arise from measures of skill in hindcasting paleo-climate changes from the present over 3 periods: the Last Glacial Maximum (LGM) (21 thousand years before present, ka), the mid-Holocene (MH) (6 ka) and the Last Millennium (LM) (850–1850 CE). The skill measures may be used to validate robust patterns of climate change across scenarios or to distinguish between models that have differing outcomes in future scenarios. We find that the multi-model ensemble of paleo-simulations is adequate for addressing at least some of these issues. For example, selected benchmarks for the LGM and MH are correlated to the rank of future projections of precipitation/temperature or sea ice extent to indicate that models that produce the best agreement with paleoclimate information give demonstrably different future results than the rest of the models. We also find that some comparisons, for instance associated with model variability, are strongly dependent on uncertain forcing timeseries, or show time dependent behaviour, making direct inferences for the future problematic. Overall, we demonstrate that there is a strong potential for the paleo-climate simulations to help inform the future projections and urge all the modeling groups to complete this subset of the CMIP5 runs.

Terahertz pulse imaging of stratified architectural materials for cultural heritage studies

Terahertz pulse imaging (TPI) is a novel noncontact, nondestructive technique for the examination of cultural heritage artifacts. It has the advantage of broadband spectral range, time-of-flight depth resolution, and penetration through optically opaque materials. Fiber-coupled, portable, time-domain terahertz systems have enabled this technique to move out of the laboratory and into the field. Much like the rings of a tree, stratified architectural materials give the chronology of their environmental and aesthetic history. This work concentrates on laboratory models of stratified mosaics and fresco paintings, specimens extracted from a neolithic excavation site in Catalhoyuk, Turkey, and specimens measured at the medieval Eglise de Saint Jean-Baptiste in Vif, France. Preparatory spectroscopic studies of various composite materials, including lime, gypsum and clay plasters are presented to enhance the interpretation of results and with the intent to aid future computer simulations of the TPI of stratified architectural material. The breadth of the sample range is a demonstration of the cultural demand and public interest in the life history of buildings. The results are an illustration of the potential role of TPI in providing both a chronological history of buildings and in the visualization of obscured wall paintings and mosaics.

The formation of ice in a long-lived supercooled layer cloud

This article focuses on the characteristics of persistent thin single-layer mixed-phase clouds. We seek to answer two important questions: (i) how does ice continually nucleate and precipitate from these clouds, without the available ice nuclei becoming depleted? (ii) how do the supercooled liquid droplets persist in spite of the net flux of water vapour to the growing ice crystals? These questions are answered quantitatively using in situ and radar observations of a long-lived mixed-phase cloud layer over the Chilbolton Observatory. Doppler radar measurements show that the top 500 m of cloud (the top 250 m of which is mixed-phase, with ice virga beneath) is turbulent and well-mixed, and the liquid water content is adiabatic. This well-mixed layer is bounded above and below by stable layers. This inhibits entrainment of fresh ice nuclei into the cloud layer, yet our in situ and radar observations show that a steady flux of ≈100 m−2s−1 ice crystals fell from the cloud over the course of ∼1 day. Comparing this flux to the concentration of conventional ice nuclei expected to be present within the well-mixed layer, we find that these nuclei would be depleted within less than 1 h. We therefore argue that nucleation in these persistent supercooled clouds is strongly time-dependent in nature, with droplets freezing slowly over many hours, significantly longer than the few seconds residence time of an ice nucleus counter. Once nucleated, the ice crystals are observed to grow primarily by vapour deposition, because of the low liquid water path (21 g m−2) yet vapour-rich environment. Evidence for this comes from high differential reflectivity in the radar observations, and in situ imaging of the crystals. The flux of vapour from liquid to ice is quantified from in situ measurements, and we show that this modest flux (3.3 g m−2h−1) can be readily offset by slow radiative cooling of the layer to space.

Comparison of the open-closed separatrix in a global magnetospheric simulation with observations: the role of the ring current

The development of global magnetospheric models, such as Space Weather Modeling Framework (SWMF), which can accurately reproduce and track space weather processes has high practical utility. We present an interval on 5 June 1998, where the location of the polar cap boundary, or open-closed field line boundary (OCB), can be determined in the ionosphere using a combination of instruments during a period encompassing a sharp northward to southward interplanetary field turning. We present both point- and time-varying comparisons of the observed and simulated boundaries in the ionosphere and find that when using solely the coupled ideal magnetohydrodynamic magnetosphere-ionosphere model, the rate of change of the OCB to a southward turning of the interplanetary field is significantly faster than that computed from the observational data. However, when the inner magnetospheric module is incorporated, the modeling framework both qualitatively, and often quantitatively, reproduces many elements of the studied interval prior to an observed substorm onset. This result demonstrates that the physics of the inner magnetosphere is critical in shaping the boundary between open and closed field lines during periods of southward interplanetary magnetic field (IMF) and provides significant insight into the 3-D time-dependent behavior of the Earth's magnetosphere in response to a northward-southward IMF turning. We assert that during periods that do not include the tens of minutes surrounding substorm expansion phase onset, the coupled SWMF model may provide a valuable and reliable tool for estimating both the OCB and magnetic field topology over a wide range of latitudes and local times.

The stability of a two-dimensional vorticity filament under uniform strain

The quantitative effects of uniform strain and background rotation on the stability of a strip of constant vorticity (a simple shear layer) are examined. The thickness of the strip decreases in time under the strain, so it is necessary to formulate the linear stability analysis for a time-dependent basic flow. The results show that even a strain rate γ (scaled with the vorticity of the strip) as small as 0.25 suppresses the conventional Rayleigh shear instability mechanism, in the sense that the r.m.s. wave steepness cannot amplify by more than a certain factor, and must eventually decay. For γ < 0.25 the amplification factor increases as γ decreases; however, it is only 3 when γ e 0.065. Numerical simulations confirm the predictions of linear theory at small steepness and predict a threshold value necessary for the formation of coherent vortices. The results help to explain the impression from numerous simulations of two-dimensional turbulence reported in the literature that filaments of vorticity infrequently roll up into vortices. The stabilization effect may be expected to extend to two- and three-dimensional quasi-geostrophic flows.

On the 'downward control' of extratropical diabatic circulations by eddy-induced mean zonal forces

The situation considered is that of a zonally symmetric model of the middle atmosphere subject to a given quasi-steady zonal force F̄, conceived to be the result of irreversible angular momentum transfer due to the upward propagation and breaking of Rossby and gravity waves together with any other dissipative eddy effects that may be relevant. The model's diabatic heating is assumed to have the qualitative character of a relaxation toward some radiatively determined temperature field. To the extent that the force F̄ may be regarded as given, and the extratropical angular momentum distribution is realistic, the extratropical diabatic mass flow across a given isentropic surface may be regarded as controlled exclusively by the F̄ distribution above that surface (implying control by the eddy dissipation above that surface and not, for instance, by the frequency of tropopause folding below). This “downward control” principle expresses a critical part of the dynamical chain of cause and effect governing the average rate at which photochemical products like ozone become available for folding into, or otherwise descending into, the extratropical troposphere. The dynamical facts expressed by the principle are also relevant, for instance, to understanding the seasonal-mean rate of upwelling of water vapor to the summer mesopause, and the interhemispheric differences in stratospheric tracer transport. The robustness of the principle is examined when F̄ is time-dependent. For a global-scale, zonally symmetric diabatic circulation with a Brewer-Dobson-like horizontal structure given by the second zonally symmetric Hough mode, with Rossby height HR = 13 km in an isothermal atmosphere with density scale height H = 7 km, the vertical partitioning of the unsteady part of the mass circulation caused by fluctuations in F̄ confined to a shallow layer LF̄ is always at least 84% downward. It is 90% downward when the force fluctuates sinusoidally on twice the radiative relaxation timescale and 95% if five times slower. The time-dependent adjustment when F̄ is changed suddenly is elucidated, extending the work of Dickinson (1968), when the atmosphere is unbounded above and below. Above the forcing, the adjustment is characterized by decay of the meridional mass circulation cell at a rate proportional to the radiative relaxation rate τr−1 divided by {1 + (4H2/HR2)}. This decay is related to the boundedness of the angular momentum that can be taken up by the finite mass of air above LF̄ without causing an ever-increasing departure from thermal wind balance. Below the forcing, the meridional mass circulation cell penetrates downward at a speed τr−1 HR2/H. For the second Hough mode, the time for downward penetration through one density scale height is about 6 days if the radiative relaxation time is 20 days, the latter being representative of the lower stratosphere. At any given altitude, a steady state is approached. The effect of a rigid lower boundary on the time-dependent adjustment is also considered. If a frictional planetary boundary layer is present then a steady state is ultimately approached everywhere, with the mass circulation extending downward from LF̄ and closing via the boundary layer. Satellite observations of temperature and ozone are used in conjunction with a radiative transfer scheme to estimate the altitudes from which the lower stratospheric diabatic vertical velocity is controlled by the effective F̄ in the real atmosphere. The data appear to indicate that about 80% of the effective control is usually exerted from below 40 km but with significant exceptions up to 70 km (in the high latitude southern hemispheric winter). The implications for numerical modelling of chemical transport are noted.

Money enhances memory consolidation – but only for boring material

Money’s ability to enhance memory has received increased attention in recent research. However, previous studies have not directly addressed the time-dependent nature of monetary effects on memory, which are suggested to exist by research in cognitive neuroscience, and the possible detrimental effects of monetary rewards on learning interesting material, as indicated by studies in motivational psychology. By utilizing a trivia question paradigm, the current study incorporated these perspectives and examined the effect of monetary rewards on immediate and delayed memory performance for answers to uninteresting and interesting questions. Results showed that monetary rewards promote memory performance only after a delay. In addition, the memory enhancement effect of monetary rewards was only observed for uninteresting questions. These results are consistent with both the hippocampus-dependent memory consolidation model of reward learning and previous findings documenting the ineffectiveness of monetary rewards on tasks that have intrinsic value.

Fireball models for flares in AE Aquarii

We examine the flaring behaviour of the cataclysmic variable AE Aqr in the context of the `magnetic propeller' model for this system. The flares are thought to arise from collisions between high-density regions in the material expelled from the system after interaction with the rapidly rotating magnetosphere of the white dwarf. We calculate the first quantitative models for the flaring and calculate the time-dependent emergent optical spectra from the resulting hot, expanding ball of gas. We compare the results under different assumptions to observations and derive values for the mass, length-scale and temperature of the material involved in the flare. We see that the fits suggest that the secondary star in this system has Population II composition.

REVIEW: Fireballs, Flares and Flickering

We review our understanding of the prototype ``Propeller'' system AE Aqr and we examine its flaring behaviour in detail. The flares are thought to arise from collisions between high density regions in the material expelled from the system after interaction with the rapidly rotating magnetosphere of the white dwarf. We show calculations of the time-dependent emergent optical spectra from the resulting hot, expanding ball of gas and derive values for the mass, lengthscale and temperature of the material involved. We see that the fits suggest that the secondary star in this system has reduced metal abundances and that, counter-intuitively, the evolution of the fireballs is best modelled as isothermal.

A moving mesh approach for modelling avascular tumour growth

A key step in many numerical schemes for time-dependent partial differential equations with moving boundaries is to rescale the problem to a fixed numerical mesh. An alternative approach is to use a moving mesh that can be adapted to focus on specific features of the model. In this paper we present and discuss two different velocity-based moving mesh methods applied to a two-phase model of avascular tumour growth formulated by Breward et al. (2002) J. Math. Biol. 45(2), 125-152. Each method has one moving node which tracks the moving boundary. The first moving mesh method uses a mesh velocity proportional to the boundary velocity. The second moving mesh method uses local conservation of volume fraction of cells (masses). Our results demonstrate that these moving mesh methods produce accurate results, offering higher resolution where desired whilst preserving the balance of fluxes and sources in the governing equations.

Coalescence of particles by differential sedimentation

We consider a three dimensional system consisting of a large number of small spherical particles, distributed in a range of sizes and heights (with uniform distribution in the horizontal direction). Particles move vertically at a size-dependent terminal velocity. They are either allowed to merge whenever they cross or there is a size ratio criterion enforced to account for collision efficiency. Such a system may be described, in mean field approximation, by the Smoluchowski kinetic equation with a differential sedimentation kernel. We obtain self-similar steady-state and time-dependent solutions to the kinetic equation, using methods borrowed from weak turbulence theory. Analytical results are compared with direct numerical simulations (DNS) of moving and merging particles, and a good agreement is found.

Bridge-localized HOMO-binding character of divinylanthracene-bridged dinuclear ruthenium carbonyl complexes: spectroscopic, spectroelectrochemical, and computational studies

The electronic properties of four divinylanthracene-bridged diruthenium carbonyl complexes [{RuCl(CO)(PMe3)3}2(μ[BOND]CH[DOUBLE BOND]CHArCH[DOUBLE BOND]CH)] (Ar=9,10-anthracene (1), 1,5-anthracene (2), 2,6-anthracene (3), 1,8-anthracene (4)) obtained by molecular spectroscopic methods (IR, UV/Vis/near-IR, and EPR spectroscopy) and DFT calculations are reported. IR spectroelectrochemical studies have revealed that these complexes are first oxidized at the noninnocent bridging ligand, which is in line with the very small ν(C[TRIPLE BOND]O) wavenumber shift that accompanies this process and also supported by DFT calculations. Because of poor conjugation in complex 1, except oxidized 1+, the electronic absorption spectra of complexes 2+, 3+, and 4+ all display the characteristic near-IR band envelopes that have been deconvoluted into three Gaussian sub-bands. Two of the sub-bands belong mainly to metal-to-ligand charge-transfer (MLCT) transitions according to results from time-dependent DFT calculations. EPR spectroscopy of chemically generated 1+–4+ proves largely ligand-centered spin density, again in accordance with IR spectra and DFT calculations results.

Estimating correlated observation error statistics using an ensemble transform Kalman filter

For certain observing types, such as those that are remotely sensed, the observation errors are correlated and these correlations are state- and time-dependent. In this work, we develop a method for diagnosing and incorporating spatially correlated and time-dependent observation error in an ensemble data assimilation system. The method combines an ensemble transform Kalman filter with a method that uses statistical averages of background and analysis innovations to provide an estimate of the observation error covariance matrix. To evaluate the performance of the method, we perform identical twin experiments using the Lorenz ’96 and Kuramoto-Sivashinsky models. Using our approach, a good approximation to the true observation error covariance can be recovered in cases where the initial estimate of the error covariance is incorrect. Spatial observation error covariances where the length scale of the true covariance changes slowly in time can also be captured. We find that using the estimated correlated observation error in the assimilation improves the analysis.