Ischaemic concentrations of lactate increase TREK1 channel activity by interacting with a single histidine residue in the carboxy terminal domain

Key points The physiological metabolite, lactate and the two-pore domain leak potassium channel, TREK1 are known neuroprotectants against cerebral ischaemia. However, it is not known whether lactate interacts with TREK1 channel to provide neuroprotection. In this study we show that lactate increases TREK1 channel activity and hyperpolarizes CA1 stratum radiatum astrocytes in hippocampal slices. Lactate increases open probability and decreases longer close time of the human (h)TREK1 channel in a concentration dependent manner. Lactate interacts with histidine 328 (H328) in the carboxy terminal domain of hTREK1 channel to decrease its dwell time in the longer closed state. This interaction was dependent on the charge on H328. Lactate-insensitive mutant H328A hTREK1 showed pH sensitivity similar to wild-type hTREK1, indicating that the effect of lactate on hTREK1 is independent of pH change. AbstractA rise in lactate concentration and the leak potassium channel TREK1 have been independently associated with cerebral ischaemia. Recent literature suggests lactate to be neuroprotective and TREK1 knockout mice show an increased sensitivity to brain and spinal cord ischaemia; however, the connecting link between the two is missing. Therefore we hypothesized that lactate might interact with TREK1 channels. In the present study, we show that lactate at ischaemic concentrations (15-30mm) at pH7.4 increases TREK1 current in CA1 stratum radiatum astrocytes and causes membrane hyperpolarization. We confirm the intracellular action of lactate on TREK1 in hippocampal slices using monocarboxylate transporter blockers and at single channel level in cell-free inside-out membrane patches. The intracellular effect of lactate on TREK1 is specific since other monocarboxylates such as pyruvate and acetate at pH7.4 failed to increase TREK1 current. Deletion and point mutation experiments suggest that lactate decreases the longer close dwell time incrementally with increase in lactate concentration by interacting with the histidine residue at position 328 (H328) in the carboxy terminal domain of the TREK1 channel. The interaction of lactate with H328 is dependent on the charge on the histidine residue since isosteric mutation of H328 to glutamine did not show an increase in TREK1 channel activity with lactate. This is the first demonstration of a direct effect of lactate on ion channel activity. The action of lactate on the TREK1 channel signifies a separate neuroprotective mechanism in ischaemia since it was found to be independent of the effect of acidic pH on channel activity. Key points The physiological metabolite, lactate and the two-pore domain leak potassium channel, TREK1 are known neuroprotectants against cerebral ischaemia. However, it is not known whether lactate interacts with TREK1 channel to provide neuroprotection. In this study we show that lactate increases TREK1 channel activity and hyperpolarizes CA1 stratum radiatum astrocytes in hippocampal slices. Lactate increases open probability and decreases longer close time of the human (h)TREK1 channel in a concentration dependent manner. Lactate interacts with histidine 328 (H328) in the carboxy terminal domain of hTREK1 channel to decrease its dwell time in the longer closed state. This interaction was dependent on the charge on H328. Lactate-insensitive mutant H328A hTREK1 showed pH sensitivity similar to wild-type hTREK1, indicating that the effect of lactate on hTREK1 is independent of pH change.

Modelling and analysis of an open-loop induction motor drive incorporating the effect of inverter dead-time

The objective of this paper is to study the influence of inverter dead-time on steady as well as dynamic operation of an open-loop induction motor drive fed from a voltage source inverter (VSI). Towards this goal, this paper presents a systematic derivation of a dynamic model for an inverter-fed induction motor, incorporating the effect of inverter dead-time, in the synchronously revolving dq reference frame. Simulation results based on this dynamic model bring out the impact of inverter dead-time on both the transient response and steady-state operation of the motor drive. For the purpose of steady-state analysis, the dynamic model of the motor drive is used to derive a steady-state model, which is found to be non-linear. The steady-state model shows that the impact of dead-time can be seen as an additional resistance in the stator circuit, whose value depends on the stator current. Towards precise evaluation of this dead-time equivalent resistance, an analytical expression is proposed for the same in terms of inverter dead-time, switching frequency, modulation index and load impedance. The notion of dead-time equivalent resistance is shown to simplify the solution of the non-linear steady-state model. The analytically evaluated steady-state solutions are validated through numerical simulations and experiments.

Campylobacter jejuni colonization and transmission in broiler chickens: a modelling perspective.

Campylobacter jejuni is one of the most common causes of acute enteritis in the developed world. The consumption of contaminated poultry, where C. jejuni is believed to be a commensal organism, is a major risk factor. However, the dynamics of this colonization process in commercially reared chickens is still poorly understood. Quantification of these dynamics of infection at an individual level is vital to understand transmission within populations and formulate new control strategies. There are multiple potential routes of introduction of C. jejuni into a commercial flock. Introduction is followed by a rapid increase in environmental levels of C. jejuni and the level of colonization of individual broilers. Recent experimental and epidemiological evidence suggest that the celerity of this process could be masking a complex pattern of colonization and extinction of bacterial strains within individual hosts. Despite the rapidity of colonization, experimental transmission studies exhibit a highly variable and unexplained delay time in the initial stages of the process. We review past models of transmission of C. jejuni in broilers and consider simple modifications, motivated by the plausible biological mechanisms of clearance and latency, which could account for this delay. We show how simple mathematical models can be used to guide the focus of experimental studies by providing testable predictions based on our hypotheses. We conclude by suggesting that competition experiments could be used to further understand the dynamics and mechanisms underlying the colonization process. The population models for such competition processes have been extensively studied in other ecological and evolutionary contexts. However, C. jejuni can potentially adapt phenotypically through phase variation in gene expression, leading to unification of ecological and evolutionary time-scales. For a theoretician, the colonization dynamics of C. jejuni offer an experimental system to explore these 'phylodynamics', the synthesis of population dynamics and evolutionary biology.

Long-range automaton models of earthquakes: Power-law accelerations, correlation evolution, and mode-switching

We introduce a conceptual model for the in-plane physics of an earthquake fault. The model employs cellular automaton techniques to simulate tectonic loading, earthquake rupture, and strain redistribution. The impact of a hypothetical crustal elastodynamic Green's function is approximated by a long-range strain redistribution law with a r(-p) dependance. We investigate the influence of the effective elastodynamic interaction range upon the dynamical behaviour of the model by conducting experiments with different values of the exponent (p). The results indicate that this model has two distinct, stable modes of behaviour. The first mode produces a characteristic earthquake distribution with moderate to large events preceeded by an interval of time in which the rate of energy release accelerates. A correlation function analysis reveals that accelerating sequences are associated with a systematic, global evolution of strain energy correlations within the system. The second stable mode produces Gutenberg-Richter statistics, with near-linear energy release and no significant global correlation evolution. A model with effectively short-range interactions preferentially displays Gutenberg-Richter behaviour. However, models with long-range interactions appear to switch between the characteristic and GR modes. As the range of elastodynamic interactions is increased, characteristic behaviour begins to dominate GR behaviour. These models demonstrate that evolution of strain energy correlations may occur within systems with a fixed elastodynamic interaction range. Supposing that similar mode-switching dynamical behaviour occurs within earthquake faults then intermediate-term forecasting of large earthquakes may be feasible for some earthquakes but not for others, in alignment with certain empirical seismological observations. Further numerical investigation of dynamical models of this type may lead to advances in earthquake forecasting research and theoretical seismology.

Effect of surface tension on the mode selection of vertically excited surface waves in a circular cylindrical vessel

Singular perturbation theory of two-time-scale expansions was developed in inviscid fluids to investigate patternforming, structure of the single surface standing wave, and its evolution with time in a circular cylindrical vessel subject to a vertical oscillation. A nonlinear slowly varying complex amplitude equation, which involves a cubic nonlinear term, an external excitation and the influence of surface tension, was derived from the potential flow equation. Surface tension was introduced by the boundary condition of the free surface in an ideal and incompressible fluid. The results show that when forced frequency is low, the effect of surface tension on the mode selection of surface waves is not important. However, when the forced frequency is high, the surface tension cannot be neglected. This manifests that the function of surface tension is to cause the free surface to return to its equilibrium configuration. In addition, the effect of surface tension seems to make the theoretical results much closer to experimental results.

Growth of liquid bridge in AFM

Capillary forces are dominant in adhesive forces measured with an atomic force microscope (AFM) in ambient air, which are thought to be dependent on water film thickness, relative humidity and the free energy of the water film. In this paper, besides these factors, we study the nature of the 'pull-off' force on a variety of atmospheres as a function of the contact time. It is found that capillary forces strongly depend on the contact time. In lower relative humidity atmosphere, the adhesion force is almost independent of the contact time. However, in higher relative humidity, the adhesion force increases with the contact time. Based on the experiment and a model that we present in this paper, the growth of the liquid bridge can be seen as undergoing two processes: one is water vapour condensation; the other is the motion of the thin liquid film that is absorbed on the substrate. The experiment and the growth model presented in this paper have direct relevance to the working mechanism of AFM in ambient air.

Sequential Monte Carlo computation of the score and observed information matrix in state-space models with application to parameter estimation

Sequential Monte Carlo (SMC) methods are popular computational tools for Bayesian inference in non-linear non-Gaussian state-space models. For this class of models, we propose SMC algorithms to compute the score vector and observed information matrix recursively in time. We propose two different SMC implementations, one with computational complexity $\mathcal{O}(N)$ and the other with complexity $\mathcal{O}(N^{2})$ where $N$ is the number of importance sampling draws. Although cheaper, the performance of the $\mathcal{O}(N)$ method degrades quickly in time as it inherently relies on the SMC approximation of a sequence of probability distributions whose dimension is increasing linearly with time. In particular, even under strong \textit{mixing} assumptions, the variance of the estimates computed with the $\mathcal{O}(N)$ method increases at least quadratically in time. The $\mathcal{O}(N^{2})$ is a non-standard SMC implementation that does not suffer from this rapid degrade. We then show how both methods can be used to perform batch and recursive parameter estimation.

An approximate likelihood method for estimating static parameters in multi-target tracking models

This paper considers a class of dynamic Spatial Point Processes (PP) that evolves over time in a Markovian fashion. This Markov in time PP is hidden and observed indirectly through another PP via thinning, displacement and noise. This statistical model is important for Multi object Tracking applications and we present an approximate likelihood based method for estimating the model parameters. The work is supported by an extensive numerical study.

Crack growth by grain boundary cavitation in the transient and extensive creep regimes

Crack growth due to cavity growth and coalescence along grain boundaries is analyzed under transient and extensive creep conditions in a compact tension specimen. Account is taken of the finite geometry changes accompanying crack tip blunting. The material is characterized as an elastic-power law creeping solid with an additional contribution to the creep rate arising from a given density of cavitating grain boundary facets. All voids are assumed present from the outset and distributed on a given density of cavitating grain boundary facets. The evolution of the stress fields with crack growth under three load histories is described in some detail for a relatively ductile material. The full-field plane strain finite element calculations show the competing effects of stress relaxation due to constrained creep, diffusion and crack tip blunting. and of stress increase due to the instantaneous elastic response to crack growth. At very high crack growth rates the Hui-Riedel fields dominate the crack tip region. However. the high growth rates are not sustained for any length of time in the compact tension geometry analyzed. The region of dominance of the Hui-Riedel field shrinks rapidly so that the near-tip fields are controlled by the HRR-type field shortly after the onset of crack growth. Crack growth rates under various conditions of loading and spanning the range of times from small scale creep to extensive creep are obtained. We show that there is a strong similarity between crack growth history and the behaviour of the C(t) and C(t) parameters. so that crack growth rates correlate rather well with C(t) and C(t). A relatively brittle material is also considered that has a very different near-tip stress field and crack growth history.

Guided pollards in the Basque Country (Spain) during the Early Modern Ages

Publicado en: "End of Tradition?.Part 1 : History of Commons and Commons Management (Cultural Severance and Commons Past)", edited by Ian D. Rotherham, Mauro Agnoletti and Christine Handley

The influence of disparate levels of submersed aquatic vegetation on largemouth bass population characteristics in a Georgia reservoir

Population characteristics of largemouth bass (Micropterous salmoides L.) including growth, body condition (relative weight), size structure, survival, and fecundity were examined in relation to abundance of submersed aquatic vegetation (SAV) coverage (primarily hydrilla Hydrilla verticillata L.f. Royle) in three major embayments of Lake Seminole, Georgia. Relative weight, fecundity, and growth of large-mouth bass in the Spring Creek embayment (76% areal SAV coverage) was considerably less than measured in the Chattahoochee and Flint river arms that contained lower SAV coverages (26% and 32%). It took fish 1.8 years longer to reach 406 mm in Spring Creek compared to the Chattahoochee-Flint arms. Consequently, fish were smaller in Spring Creek than in the Chattahoochee-Flint arms. In addition, due to slower growth rates and lower fecundity-to-body weight relation, we predicted a 47% reduction in total potential ova production in Spring Creek compared to the other two reservoir embayments. The annual survival rate of 3 to 10 year old largemouth bass was higher in Spring Creek (84%) than in the Chattahoochee-Flint arms (72%) and suggested either lower harvest and/or lower accessibility of particularly larger fish to angling in dense vegetation. Contrary to our expectaions, the fit between number-at-age and age in a catch-curve regression was weaker for fish collected in Spring Creek and suggested greater recruitment variability has occurred over time in this highly vegetated embayment. In Lake Seminole, spatial differences in largemouth bass population characterstics were associated with disparate levels of SAV. Our data suggest that a reduction in hydrilla, but maintenance of an intermediate level of SAV in Spring Creek, should improve largermouth bass population in this arm of the reservoir.

Eurasian watermilfoil biomass associated with insect herbivores in New York

A study of aquatic plant biomass within Cayuga Lake, New York spans twelve years from 1987-1998. The exotic Eurasian watermilfoil ( Myriophyllum spicatum L.) decreased in the northwest end of the lake from 55% of the total biomass in 1987 to 0.4% in 1998 and within the southwest end from 50% in 1987 to 11% in 1998. Concurrent with the watermilfoil decline was the resurgence of native species of submersed macrophytes. During this time we recorded for the first time in Cayuga Lake two herbivorous insect species: the aquatic moth Acentria ephemerella , first observed in 1991, and the aquatic weevil Euhrychiopsis lecontei , first found in 1996 . Densities of Acentria in southwest Cayuga Lake averaged 1.04 individuals per apical meristem of Eurasian watermilfoil for the three-year period 1996-1998. These same meristems had Euhrychiopsis densities on average of only 0.02 individuals per apical meristem over the same three-year period. A comparison of herbivore densities and lake sizes from five lakes in 1997 shows that Acentria densities correlate positively with lake surface area and mean depth, while Euhrychiopsis densities correlate negatively with lake surface area and mean depth. In these five lakes, Acentria densities correlate negatively with percent composition and dry mass of watermilfoil. However, Euhrychiopsis densities correlate positively with percent composition and dry mass of watermilfoil. Finally, Acentria densities correlate negatively with Euhrychiopsis densities suggesting interspecific competition.

Improvements to Data Collection in Commercial Fisheries Using Electronic Reporting Methods: Cost/Efficiency and Implications for Use in Ecosystem Management.

Data have been collected on fisheries catch and effort trends since the latter half of the 1800s. With current trends in declining stocks and stricter management regimes, data need to be collected and analyzed over shorter periods and at finer spatial resolution than in the past. New methods of electronic reporting may reduce the lag time in data collection and provide more accurate spatial resolution. In this study I evaluated the differences between fish dealer and vessel reporting systems for federal fisheries in the US New England and Mid-Atlantic areas. Using data on landing date, report date, gear used, port landed, number of hauls, number of fish sampled and species quotas from available catch and effort records I compared dealer and vessel electronically collected data against paper collected dealer and vessel data to determine if electronically collected data are timelier and more accurate. To determine if vessel or dealer electronic reporting is more useful for management, I determined differences in timeliness and accuracy between vessel and dealer electronic reports. I also compared the cost and efficiency of these new methods with less technology intensive reporting methods using available cost data and surveys of seafood dealers for cost information. Using this information I identified potentially unnecessary duplication of effort and identified applications in ecosystem-based fisheries management. This information can be used to guide the decisions of fisheries managers in the United States and other countries that are attempting to identify appropriate fisheries reporting methods for the management regimes under consideration. (PDF contains 370 pages)