Statins and selective inhibition of Rho kinase protect small conductance calcium-activated potassium channel function (KCa2.3) in cerebral arteries

Background: In rat middle cerebral and mesenteric arteries the KCa2.3 component of endothelium-dependent hyperpolarization (EDH) is lost following stimulation of thromboxane (TP) receptors, an effect that may contribute to the endothelial dysfunction associated with cardiovascular disease. In cerebral arteries, KCa2.3 loss is associated with NO synthase inhibition, but is restored if TP receptors are blocked. The Rho/Rho kinase pathway is central for TP signalling and statins indirectly inhibit this pathway. The possibility that Rho kinase inhibition and statins sustain KCa2.3 hyperpolarization was investigated in rat middle cerebral arteries (MCA). Methods: MCAs were mounted in a wire myograph. The PAR2 agonist, SLIGRL was used to stimulate EDH responses, assessed by simultaneous measurement of smooth muscle membrane potential and tension. TP expression was assessed with rt-PCR and immunofluorescence. Results: Immunofluorescence detected TP in the endothelial cell layer of MCA. Vasoconstriction to the TP agonist, U46619 was reduced by Rho kinase inhibition. TP receptor stimulation lead to loss of KCa2.3 mediated hyperpolarization, an effect that was reversed by Rho kinase inhibitors or simvastatin. KCa2.3 activity was lost in L-NAME-treated arteries, but was restored by Rho kinase inhibition or statin treatment. The restorative effect of simvastatin was blocked after incubation with geranylgeranyl-pyrophosphate to circumvent loss of isoprenylation. Conclusions: Rho/Rho kinase signalling following TP stimulation and L-NAME regulates endothelial cell KCa2.3 function. The ability of statins to prevent isoprenylation and perhaps inhibit of Rho restores/protects the input of KCa2.3 to EDH in the MCA, and represents a beneficial pleiotropic effect of statin treatment.

Layer-by-layer coating of alginate matrices with chitosan–alginate for the improved survival and targeted delivery of probiotic bacteria after oral administration

The oral administration of probiotic bacteria has shown potential in clinical trials for the alleviation of specific disorders of the gastrointestinal tract. However, cells must be alive in order to exert these benefits. The low pH of the stomach can greatly reduce the number of viable microorganisms that reach the intestine, thereby reducing the efficacy of the administration. Herein, a model probiotic, Bifidobacterium breve, has been encapsulated into an alginate matrix before coating in multilayers of alternating alginate and chitosan. The intention of this formulation was to improve the survival of B. breve during exposure to low pH and to target the delivery of the cells to the intestine. The material properties were first characterized before in vitro testing. Biacore™ experiments allowed for the polymer interactions to be confirmed; additionally, the stability of these multilayers to buffers simulating the pH of the gastrointestinal tract was demonstrated. Texture analysis was used to monitor changes in the gel strength during preparation, showing a weakening of the matrices during coating as a result of calcium ion sequestration. The build-up of multilayers was confirmed by confocal laser-scanning microscopy, which also showed the increase in the thickness of coat over time. During exposure to in vitro gastric conditions, an increase in viability from <3 log(CFU) per mL, seen in free cells, up to a maximum of 8.84 ± 0.17 log(CFU) per mL was noted in a 3-layer coated matrix. Multilayer-coated alginate matrices also showed a targeting of delivery to the intestine, with a gradual release of their loads over 240 min.

Middle and Late Cenomanian anoxia in shallow and deeper shelf environments of western Morocco

The response of shallow-water sequences to oceanic anoxic event 2 and mid-Cenomanian events 1a and 1b was investigated along the west African margin of Morocco north of Agadir (Azazoul) and correlated with the deep-water sequence of the Tarfaya Basin (Mohammed Beach) based on biostratigraphy, mineralogy, phosphorus and stable isotopes. In the deeper Mohammed Beach section results show double peaks in δ13Corg for mid-Cenomanian events 1a and 1b (Rotalipora reicheli biozone, lower CC10a biozone), the characteristic oceanic anoxic event 2 δ13C excursion (Rotalipora cushmani extinction, top of CC10a biozone) and laminated (anoxic) black shale. In the shallow environment north of Agadir, a fluctuating sea-level associated with dysoxic, brackish and mesotrophic conditions prevailed during the middle to late Cenomanian, as indicated by oyster biostromes, nannofossils, planktonic and benthonic foraminiferal assemblages. Anoxic conditions characteristic of oceanic anoxic event 2 (for example, laminated black shales) did not reach into shallow-water environments until the maximum transgression of the early Turonian. Climate conditions decoupled along the western margin of Morocco between mid-Cenomanian event 1b and the Cenomanian–Turonian boundary, as also observed in eastern Tethys. North of Agadir alternating humid and dry seasonal conditions prevailed, whereas in the Tarfaya Basin the climate was dry and seasonal. This climatic decoupling can be attributed to variations in the Intertropical Convergence Zone and in the intensity of the north-east trade winds in tropical areas.

Comparison of different boundary layer surface schemes using single point micrometeorological field data

 In the last decade, a vast number of land surface schemes has been designed for use in global climate models, atmospheric weather prediction, mesoscale numerical models, ecological models, and models of global changes. Since land surface schemes are designed for different purposes they have various levels of complexity in the treatment of bare soil processes, vegetation, and soil water movement. This paper is a contribution to a little group of papers dealing with intercomparison of differently designed and oriented land surface schemes. For that purpose we have chosen three schemes for classification: i) global climate models, BATS (Dickinson et al., 1986; Dickinson et al., 1992); ii) mesoscale and ecological models, LEAF (Lee, 1992) and iii) mesoscale models, LAPS (Mihailović, 1996; Mihailović and Kallos, 1997; Mihailović et al., 1999) according to the Shao et al. (1995) classification. These schemes were compared using surface fluxes and leaf temperature outputs obtained by time integrations of data sets derived from the micrometeorological measurements above a maize field at an experimental site in De Sinderhoeve (The Netherlands) for 18 August, 8 September, and 4 October 1988. Finally, comparison of the schemes was supported applying a simple statistical analysis on the surface flux outputs.

The unsteady flow of a weakly compressible fluid in a thin porous layer II: three-dimensional theory

We consider the problem of determining the pressure and velocity fields for a weakly compressible fluid flowing in a three-dimensional layer, composed of an inhomogeneous, anisotropic porous medium, with vertical side walls and variable upper and lower boundaries, in the presence of vertical wells injecting and/or extracting fluid. Numerical solution of this three-dimensional evolution problem may be expensive, particularly in the case that the depth scale of the layer h is small compared to the horizontal length scale l, a situation which occurs frequently in the application to oil and gas reservoir recovery and which leads to significant stiffness in the numerical problem. Under the assumption that $\epsilon\propto h/l\ll 1$, we show that, to leading order in $\epsilon$, the pressure field varies only in the horizontal directions away from the wells (the outer region). We construct asymptotic expansions in $\epsilon$ in both the inner (near the wells) and outer regions and use the asymptotic matching principle to derive expressions for all significant process quantities. The only computations required are for the solution of non-stiff linear, elliptic, two-dimensional boundary-value, and eigenvalue problems. This approach, via the method of matched asymptotic expansions, takes advantage of the small aspect ratio of the layer, $\epsilon$, at precisely the stage where full numerical computations become stiff, and also reveals the detailed structure of the dynamics of the flow, both in the neighbourhood of wells and away from wells.

The unsteady flow of a weakly compressible fluid in a thin porous layer III: three-dimensional computations

We describe a novel method for determining the pressure and velocity fields for a weakly compressible fluid flowing in a thin three-dimensional layer composed of an inhomogeneous, anisotropic porous medium, with vertical side walls and variable upper and lower boundaries, in the presence of vertical wells injecting and/or extracting fluid. Our approach uses the method of matched asymptotic expansions to derive expressions for all significant process quantities, the computation of which requires only the solution of linear, elliptic, two-dimensional boundary value and eigenvalue problems. In this article, we provide full implementation details and present numerical results demonstrating the efficiency and accuracy of our scheme.

Influence of the Antarctic ozone hole on the polar mesopause region as simulated by the Canadian Middle Atmosphere Model

It is well established that variations in polar stratospheric winds can affect mesospheric temperatures through changes in the filtering of gravity wave fluxes, which drive a residual circulation in the mesosphere. The Canadian Middle Atmosphere Model(CMAM) is used to examine this vertical coupling mechanism in the context of the mesospheric response to the Antarctic ozone hole. It is found that the response differs significantly between late spring and early summer, because of a changing balance between the competing effects of parametrised gravity wavedrag (GWD)and changes in resolved wave drag local to the mesosphere. In late spring, the strengthened stratospheric westerlies arising from the ozone hole lead to reduced eastward GWD in the mesosphere and a warming of the polar mesosphere, just as in the well known mesospheric response to sudden stratospheric warmings, but with an opposite sign.In early summer, with easterly flow revailing over most of the polar stratosphere,the strengthened easterly wind shear within the mesosphere arising from the west ward GWD anomaly induces a positive resolved wave drag anomaly through baroclinic instability. The polar cooling induced by this process completely dominates the upper mesospheric response to the ozone hole in early summer. Consequences for the past and future evolution of noctilucent clouds are discussed

A robust mechanism for strengthening of the Brewer–Dobson circulation in response to climate change: critical-layer control of subtropical wave breaking

Climate models consistently predict a strengthened Brewer–Dobson circulation in response to greenhouse gas (GHG)-induced climate change. Although the predicted circulation changes are clearly the result of changes in stratospheric wave drag, the mechanism behind the wave-drag changes remains unclear. Here, simulations from a chemistry–climate model are analyzed to show that the changes in resolved wave drag are largely explainable in terms of a simple and robust dynamical mechanism, namely changes in the location of critical layers within the subtropical lower stratosphere, which are known from observations to control the spatial distribution of Rossby wave breaking. In particular, the strengthening of the upper flanks of the subtropical jets that is robustly expected from GHG-induced tropospheric warming pushes the critical layers (and the associated regions of wave drag) upward, allowing more wave activity to penetrate into the subtropical lower stratosphere. Because the subtropics represent the critical region for wave driving of the Brewer–Dobson circulation, the circulation is thereby strengthened. Transient planetary-scale waves and synoptic-scale waves generated by baroclinic instability are both found to play a crucial role in this process. Changes in stationary planetary wave drag are not so important because they largely occur away from subtropical latitudes.

On the approximation of local and linear radiative damping in the middle atmosphere

The validity of approximating radiative heating rates in the middle atmosphere by a local linear relaxation to a reference temperature state (i.e., ‘‘Newtonian cooling’’) is investigated. Using radiative heating rate and temperature output from a chemistry–climate model with realistic spatiotemporal variability and realistic chemical and radiative parameterizations, it is found that a linear regressionmodel can capture more than 80% of the variance in longwave heating rates throughout most of the stratosphere and mesosphere, provided that the damping rate is allowed to vary with height, latitude, and season. The linear model describes departures from the climatological mean, not from radiative equilibrium. Photochemical damping rates in the upper stratosphere are similarly diagnosed. Threeimportant exceptions, however, are found.The approximation of linearity breaks down near the edges of the polar vortices in both hemispheres. This nonlinearity can be well captured by including a quadratic term. The use of a scale-independentdamping rate is not well justified in the lower tropical stratosphere because of the presence of a broad spectrum of vertical scales. The local assumption fails entirely during the breakup of the Antarctic vortex, where large fluctuations in temperature near the top of the vortex influence longwave heating rates within the quiescent region below. These results are relevant for mechanistic modeling studies of the middle atmosphere, particularly those investigating the final Antarctic warming.

Some numerical experiments on the effect of the variation of static stability in two-layer quasi-geostrophic models

A method to solve a quasi-geostrophic two-layer model including the variation of static stability is presented. The divergent part of the wind is incorporated by means of an iterative procedure. The procedure is rather fast and the time of computation is only 60–70% longer than for the usual two-layer model. The method of solution is justified by the conservation of the difference between the gross static stability and the kinetic energy. To eliminate the side-boundary conditions the experiments have been performed on a zonal channel model. The investigation falls mainly into three parts: The first part (section 5) contains a discussion of the significance of some physically inconsistent approximations. It is shown that physical inconsistencies are rather serious and for these inconsistent models which were studied the total kinetic energy increased faster than the gross static stability. In the next part (section 6) we are studying the effect of a Jacobian difference operator which conserves the total kinetic energy. The use of this operator in two-layer models will give a slight improvement but probably does not have any practical use in short periodic forecasts. It is also shown that the energy-conservative operator will change the wave-speed in an erroneous way if the wave-number or the grid-length is large in the meridional direction. In the final part (section 7) we investigate the behaviour of baroclinic waves for some different initial states and for two energy-consistent models, one with constant and one with variable static stability. According to the linear theory the waves adjust rather rapidly in such a way that the temperature wave will lag behind the pressure wave independent of the initial configuration. Thus, both models give rise to a baroclinic development even if the initial state is quasi-barotropic. The effect of the variation of static stability is very small, qualitative differences in the development are only observed during the first 12 hours. For an amplifying wave we will get a stabilization over the troughs and an instabilization over the ridges.

Past and future conditions for polar stratospheric cloud formation simulated by the Canadian Middle Atmosphere Model

We analyze here the polar stratospheric temperatures in an ensemble of three 150-year integrations of the Canadian Middle Atmosphere Model (CMAM), an interactive chemistry-climate model which simulates ozone depletion and recovery, as well as climate change. A key motivation is to understand possible mechanisms for the observed trend in the extent of conditions favourable for polar stratospheric cloud (PSC) formation in the Arctic winter lower stratosphere. We find that in the Antarctic winter lower stratosphere, the low temperature extremes required for PSC formation increase in the model as ozone is depleted, but remain steady through the twenty-first century as the warming from ozone recovery roughly balances the cooling from climate change. Thus, ozone depletion itself plays a major role in the Antarctic trends in low temperature extremes. The model trend in low temperature extremes in the Arctic through the latter half of the twentieth century is weaker and less statistically robust than the observed trend. It is not projected to continue into the future. Ozone depletion in the Arctic is weaker in the CMAM than in observations, which may account for the weak past trend in low temperature extremes. In the future, radiative cooling in the Arctic winter due to climate change is more than compensated by an increase in dynamically driven downwelling over the pole.

Seasonal persistence of northern low- and middle-latitude anomalies of ozone and other trace gases in the upper stratosphere

Analysis of observed ozone profiles in Northern Hemisphere low and middle latitudes reveals the seasonal persistence of ozone anomalies in both the lower and upper stratosphere. Principal component analysis is used to detect that above 16 hPa the persistence is strongest in the latitude band 15–45°N, while below 16 hPa the strongest persistence is found over 45–60°N. In both cases, ozone anomalies persist through the entire year from November to October. The persistence of ozone anomalies in the lower stratosphere is presumably related to the wintertime ozone buildup with subsequent photochemical relaxation through summer, as previously found for total ozone. The persistence in the upper stratosphere is more surprising, given the short lifetime of Ox at these altitudes. It is hypothesized that this “seasonal memory” in the upper stratospheric ozone anomalies arises from the seasonal persistence of transport-induced wintertime NOy anomalies, which then perturb the ozone chemistry throughout the rest of the year. This hypothesis is confirmed by analysis of observations of NO2, NOx, and various long-lived trace gases in the upper stratosphere, which are found to exhibit the same seasonal persistence. Previous studies have attributed much of the year-to-year variability in wintertime extratropical upper stratospheric ozone to the Quasi-Biennial Oscillation (QBO) through transport-induced NOy (and hence NO2) anomalies but have not identified any statistical connection between the QBO and summertime ozone variability. Our results imply that through this “seasonal memory,” the QBO has an asynchronous effect on ozone in the low to midlatitude upper stratosphere during summer and early autumn.

Transport in the middle atmosphere

An overview is provided of the current understanding of transport in the middle atmosphere. Over the past quarter century this subject has evolved from a basic recognition of the Brewer-Dobson circulation to a detailed appreciation of many key features of transport such as the stratospheric surf zone, mixing barriers and the dynamics of filamentation. Whilst the elegant theoretical framework for middle atmosphere transport that emerged roughly twenty years ago never fulfilled its promise, useful phenomenological models have been developed together with innovative diagnostic methods. These advances were made possible by the advent of plenty of satellite and aircraft observations of long-lived chemical species together with developments in data assimilation and numerical modeling, and have been driven in large measure by the problem of stratospheric ozone depletion. This review is primarily focused on the stratosphere, where both the interest and the knowledge are the greatest, but a few remarks are also made on the mesosphere.