HL-1 cells express an inwardly rectifying K+ current activated via muscarinic receptors comparable to that in mouse atrial myocytes

An inwardly rectifying K^+ current is present in atrial cardiac myocytes that is activated by acetylcholine (I_{KACh}). Physiologically, activation of the current in the SA node is important in slowing the heart rate with increased parasympathetic tone. It is a paradigm for the direct regulation of signaling effectors by the Gβγ G-protein subunit. Many questions have been addressed in heterologous expression systems with less focus on the behaviour in native myocytes partly because of the technical difficulties in undertaking comparable studies in native cells. In this study, we characterise a potassium current in the atrial-derived cell line HL-1. Using an electrophysiological approach, we compare the characteristics of the potassium current with those in native atrial cells and in a HEK cell line expressing the cloned Kir3.1/3.4 channel. The potassium current recorded in HL-1 is inwardly rectifying and activated by the muscarinic agonist carbachol. Carbachol-activated currents were inhibited by pertussis toxin and tertiapin-Q. The basal current was time-dependently increased when GTP was substituted in the patch-clamp pipette by the non-hydrolysable analogue GTPγS. We compared the kinetics of current modulation in HL-1 with those of freshly isolated atrial mouse cardiomyocytes. The current activation and deactivation kinetics in HL-1 cells are comparable to those measured in atrial cardiomyocytes. Using immunofluorescence, we found GIRK4 at the membrane in HL-1 cells. Real-time RT-PCR confirms the presence of mRNA for the main G-protein subunits, as well as for M2 muscarinic and A1 adenosine receptors. The data suggest HL-1 cells are a good model to study IKAch

Quadratic algebras related to elliptic curves

We construct quadratic finite-dimensional Poisson algebras and their quantum versions related to rank N and degree one vector bundles over elliptic curves with n marked points. The algebras are parameterized by the moduli of curves. For N=2 and n=1 they coincide with the Sklyanin algebras. We prove that the Poisson structure is compatible with the Lie-Poisson structure on the direct sum of n copies of sl(N). The derivation is based on the Poisson reduction from the canonical brackets on the affine space over the cotangent bundle to the groups of automorphisms of vector bundles.Comment: 21 page

Interplanetary particle transport simulation for warning system for aviation exposure to solar energetic particles

Solar energetic particles (SEPs) are one of the extreme space weather phenomena. A huge SEP event increases the radiation dose received by aircrews, who should be warned of such events as early as possible. We developed a warning system for aviation exposure to SEPs. This article describes one component of the system, which calculates the temporal evolution of the SEP intensity and the spectrum immediately outside the terrestrial magnetosphere. To achieve this, we performed numerical simulations of SEP transport in interplanetary space, in which interplanetary SEP transport is described by the focused transport equation. We developed a new simulation code to solve the equation using a set of stochastic differential equations. In the code, the focused transport equation is expressed in a magnetic field line coordinate system, which is a non-orthogonal curvilinear coordinate system. An inverse Gaussian distribution is employed as the injection profile of SEPs at an inner boundary located near the Sun. We applied the simulation to observed SEP events as a validation test. The results show that our simulation can closely reproduce observational data for the temporal evolution of particle intensity. By employing the code, we developed the WArning System for AVIation Exposure to Solar energetic particles (WASAVIES).Comment: 23 pages, 11 figures, accepted for publication in Earth, Planets and Spac

Infinite genus surfaces and irrational polygonal billiards

We prove that the natural invariant surface associated with the billiard game on an irrational polygonal table is homeomorphic to the Loch Ness monster, that is, the only orientable infinite genus topological real surface with exactly one end.Comment: 15 pages, 18 figure

Stops making sense: translational trade-offs and stop codon reassignment

Background Efficient gene expression involves a trade-off between (i) premature termination of protein synthesis; and (ii) readthrough, where the ribosome fails to dissociate at the terminal stop. Sense codons that are similar in sequence to stop codons are more susceptible to nonsense mutation, and are also likely to be more susceptible to transcriptional or translational errors causing premature termination. We therefore expect this trade-off to be influenced by the number of stop codons in the genetic code. Although genetic codes are highly constrained, stop codon number appears to be their most volatile feature. Results In the human genome, codons readily mutable to stops are underrepresented in coding sequences. We construct a simple mathematical model based on the relative likelihoods of premature termination and readthrough. When readthrough occurs, the resultant protein has a tail of amino acid residues incorrectly added to the C-terminus. Our results depend strongly on the number of stop codons in the genetic code. When the code has more stop codons, premature termination is relatively more likely, particularly for longer genes. When the code has fewer stop codons, the length of the tail added by readthrough will, on average, be longer, and thus more deleterious. Comparative analysis of taxa with a range of stop codon numbers suggests that genomes whose code includes more stop codons have shorter coding sequences. Conclusions We suggest that the differing trade-offs presented by alternative genetic codes may result in differences in genome structure. More speculatively, multiple stop codons may mitigate readthrough, counteracting the disadvantage of a higher rate of nonsense mutation. This could help explain the puzzling overrepresentation of stop codons in the canonical genetic code and most variants

Health care operations management

Health care operations management has become a major topic for health care service providers and society. Operations research already has and further will make considerable contributions for the effective and efficient delivery of health care services. This special issue collects seven carefully selected papers dealing with optimization and decision analysis problems in the field of health care operations management

Designing an information system for updating land records in Bangladesh: action design ethnographic research (ADER)

Open Access. This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.This article has been made available through the Brunel Open Access Publishing Fund.Information Systems (IS) has developed through adapting, generating and applying diverse methodologies, methods, and techniques from reference disciplines. Further, Action Design Research (ADR) has recently developed as a broad research method that focuses on designing and redesigning IT and IS in organizational contexts. This paper reflects on applying ADR in a complex organizational context in a developing country. It shows that ADR requires additional lens for designing IS in such a complex organizational context. Through conducting ADR, it is seen that an ethnographic framework has potential complementarities for understanding complex contexts thereby enhancing the ADR processes. This paper argues that conducting ADR with an ethnographic approach enhances design of IS and organizational contexts. Finally, this paper aims presents a broader methodological framework, Action Design Ethnographic Research (ADER), for designing artefacts as well as IS. This is illustrated through the case of a land records updating service in Bangladesh

Complete intersection vanishing ideals on degenerate tori over finite fields

We study the complete intersection property and the algebraic invariants (index of regularity, degree) of vanishing ideals on degenerate tori over finite fields. We establish a correspondence between vanishing ideals and toric ideals associated to numerical semigroups. This correspondence is shown to preserve the complete intersection property, and allows us to use some available algorithms to determine whether a given vanishing ideal is a complete intersection. We give formulae for the degree, and for the index of regularity of a complete intersection in terms of the Frobenius number and the generators of a numerical semigroup.Comment: Arabian Journal of Mathematics, to appea

On the Saturation of Astrophysical Dynamos: Numerical Experiments with the No-cosines flow

In the context of astrophysical dynamos we illustrate that the no-cosines flow, with zero mean helicity, can drive fast dynamo action and study the dynamo's mode of operation during both the linear and non-linear saturation regime: It turns out that in addition to a high growth rate in the linear regime, the dynamo saturates at a level significantly higher than normal turbulent dynamos, namely at exact equipartition when the magnetic Prandtl number is on the order of unity. Visualization of the magnetic and velocity fields at saturation will help us to understand some of the aspects of the non-linear dynamo problem.Comment: 8 pages, 5 figures, submitted to the proceedings of "Space Climate 1" to be peer-reviewed to Solar Physic

Shedding light on walking in the dark: the effects of reduced lighting on the gait of older adults with a higher-level gait disorder and controls

OBJECTIVE: To study the effects of reduced lighting on the gait of older adults with a high level gait disorder (HLGD) and to compare their response to that of healthy elderly controls. METHODS: 22 patients with a HLGD and 20 age-matched healthy controls were studied under usual lighting conditions (1000 lumens) and in near darkness (5 lumens). Gait speed and gait dynamics were measured under both conditions. Cognitive function, co-morbidities, depressive symptoms, and vision were also evaluated. RESULTS: Under usual lighting conditions, patients walked more slowly, with reduced swing times, and increased stride-to-stride variability, compared to controls. When walking under near darkness conditions, both groups slowed their gait. All other measures of gait were not affected by lighting in the controls. In contrast, patients further reduced their swing times and increased their stride-to-stride variability, both stride time variability and swing time variability. The unique response of the patients was not explained by vision, mental status, co-morbidities, or the values of walking under usual lighting conditions. CONCLUSION: Walking with reduced lighting does not affect the gait of healthy elderly subjects, except for a reduction in speed. On the other hand, the gait of older adults with a HLGD becomes more variable and unsteady when they walk in near darkness, despite adapting a slow and cautious gait. Further work is needed to identify the causes of the maladaptive response among patients with a HLGD and the potential connection between this behavior and the increased fall risk observed in these patients