Electrophysiological and arrhythmogenic effects of 5-hydroxytryptamine on human atrial cells are reduced in atrial fibrillation

5-Hydroxytryptamine (5-HT) is proarrhythmic in atrial cells from patients in sinus rhythm (SR) via activation of 5-HT<sub>4</sub> receptors, but its effects in atrial cells from patients with atrial fibrillation (AF) are unknown. The whole-cell perforated patch-clamp technique was used to record L-type Ca<sup>2+</sup> current (<i>I</i><sub>CaL</sub>), action potential duration (APD) and arrhythmic activity at 37 °C in enzymatically isolated atrial cells obtained from patients undergoing cardiac surgery, in SR or with chronic AF. In the AF group, 5-HT (10 μM) produced an increase in <i>I</i><sub>CaL</sub> of 115 ± 21% above control (<i>n</i> = 10 cells, 6 patients) that was significantly smaller than that in the SR group (232 ± 33%; <i>p</i> 0.05; <i>n</i> = 27 cells, 12 patients). Subsequent co-application of isoproterenol (1 μM) caused a further increase in <i>I</i><sub>CaL</sub> in the AF group (by 256 ± 94%) that was greater than that in the SR group (22 ± 6%; p < 0.05). The APD at 50% repolarisation (APD<sub>50</sub>) was prolonged by 14 ± 3 ms by 5-HT in the AF group (<i>n</i> = 37 cells, 14 patients). This was less than that in the SR group (27 ± 4 ms; <i>p</i> < 0.05; <i>n</i> = 58 cells, 24 patients). Arrhythmic activity in response to 5-HT was observed in 22% of cells in the SR group, but none was observed in the AF group (p < 0.05). Atrial fibrillation was associated with reduced effects of 5-HT, but not of isoproterenol, on <i>I</i><sub>CaL</sub> in human atrial cells. This reduced effect on <i>I</i><sub>CaL</sub> was associated with a reduced APD<sub>50</sub> and arrhythmic activity with 5-HT. Thus, the potentially arrhythmogenic influence of 5-HT may be suppressed in AF-remodelled human atrium

Epicyclic oscillations of non-slender fluid tori around Kerr black holes

Considering epicyclic oscillations of pressure-supported perfect fluid tori orbiting Kerr black holes we examine non-geodesic (pressure) effects on the epicyclic modes properties. Using a perturbation method we derive fully general relativistic formulas for eigenfunctions and eigenfrequencies of the radial and vertical epicyclic modes of a slightly non-slender, constant specific angular momentum torus up to second-order accuracy with respect to the torus thickness. The behaviour of the axisymmetric and lowest-order ($m=\pm 1$) non-axisymmetric epicyclic modes is investigated. For an arbitrary black hole spin we find that, in comparison with the (axisymmetric) epicyclic frequencies of free test particles, non-slender tori receive negative pressure corrections and exhibit thus lower frequencies. Our findings are in qualitative agreement with the results of a recent pseudo-Newtonian study of analogous problem defined within the Paczy{\'n}ski-Wiita potential. Implications of our results on the high-frequency QPO models dealing with epicyclic oscillations are addressed.Comment: 24 pages, 8 figure

Cellular bases for human atrial fibrillation

Atrial fibrillation (AF) causes substantial morbidity and mortality. It may be triggered and sustained by either reentrant or nonreentrant electrical activity. Human atrial cellular refractory period is shortened in chronic AF, likely aiding reentry. The ionic and molecular mechanisms are not fully understood and may include increased inward rectifier K<sup>+</sup> current and altered Ca<sup>2+</sup> handling. Heart failure, a major cause of AF, may involve arrhythmogenic atrial electrical remodeling, but the pattern is unclear in humans. Beta-blocker therapy prolongs atrial cell refractory period; a potentially antiarrhythmic influence, but the ionic and molecular mechanisms are unclear. The search for drugs to suppress AF without causing ventricular arrhythmias has been aided by basic studies of cellular mechanisms of AF. It remains to be seen whether such drugs will improve patient treatment

Contrasting carbonate depositional systems for Pliocene cool-water limestones cropping out in central Hawke's Bay, New Zealand

Pliocene limestone formations in central Hawke's Bay (eastern North Island, New Zealand) accumulated on and near the margins of a narrow forearc basin seaway within the convergent Australia/Pacific plate boundary zone. The active tectonic setting and varied paleogeographic features of the limestone units investigated, in association with probable glacioeustatic sea-level fluctuations, resulted in complex stratigraphic architectures and contrasting types of carbonate accumulation on either side of the seaway. Here, we recognise recurring patterns of sedimentary facies, and sequences and systems tracts bounded by key physical surfaces within the limestone sheets. The facies types range from Bioclastic (B) to Siliciclastic (S) end-members via Mixed (M) carbonate-siliciclastic deposits. Skeletal components are typical cool-water associations dominated by epifaunal calcitic bivalves, bryozoans, and especially barnacles. Siliciclastic contents vary from one formation to another, and highlight siliciclastic-rich limestone units in the western ranges versus siliciclastic-poor limestone units in the eastern coastal hills. Heterogeneities in facies types, stratal patterns, and also in diagenetic pathways between eastern and western limestone units are considered to originate in the coeval occurrence in different parts of the forearc basin of two main morphodynamic carbonate systems over time

Bounding the mass of the graviton using gravitional-wave observations of inspiralling compact binaries

If gravitation is propagated by a massive field, then the velocity of gravitational waves (gravitons) will depend upon their frequency and the effective Newtonian potential will have a Yukawa form. In the case of inspiralling compact binaries, gravitational waves emitted at low frequency early in the inspiral will travel slightly slower than those emitted at high frequency later, modifying the phase evolution of the observed inspiral gravitational waveform, similar to that caused by post-Newtonian corrections to quadrupole phasing. Matched filtering of the waveforms can bound such frequency-dependent variations in propagation speed, and thereby bound the graviton mass. The bound depends on the mass of the source and on noise characteristics of the detector, but is independent of the distance to the source, except for weak cosmological redshift effects. For observations of stellar-mass compact inspiral using ground-based interferometers of the LIGO/VIRGO type, the bound on the graviton Compton wavelength is of the order of $6 \times 10^{12}$ km, about double that from solar-system tests of Yukawa modifications of Newtonian gravity. For observations of super-massive black hole binary inspiral at cosmological distances using the proposed laser interferometer space antenna (LISA), the bound can be as large as $6 \times 10^{16}$ km. This is three orders of magnitude weaker than model-dependent bounds from galactic cluster dynamics.Comment: 8 pages, RevTeX, submitted to Phys. Rev.

Juxtaposition of Chemical and Mutation-Induced Developmental Defects in Zebrafish Reveal a Copper-Chelating Activity for Kalihinol F

SummaryA major hurdle in using complex systems for drug screening is the difficulty of defining the mechanistic targets of small molecules. The zebrafish provides an excellent model system for juxtaposing developmental phenotypes with mechanism discovery using organism genetics. We carried out a phenotype-based screen of uncharacterized small molecules in zebrafish that produced a variety of chemically induced phenotypes with potential genetic parallels. Specifically, kalihinol F caused an undulated notochord, defects in pigment formation, hematopoiesis, and neural development. These phenotypes were strikingly similar to the zebrafish mutant, calamity, an established model of copper deficiency. Further studies into the mechanism of action of kalihinol F revealed a copper-chelating activity. Our data support this mechanism of action for kalihinol F and the utility of zebrafish as an effective system for identifying therapeutic and target pathways

Anatomy and origin of authochthonous late Pleistocene forced regression deposits, east Coromandel inner shelf, New Zealand: implications for the development and definition of the regressive systems tract

High-resolution seismic reflection data from the east Coromandel coast, New Zealand, provide details of the sequence stratigraphy beneath an autochthonous, wave dominated inner shelf margin during the late Quaternary (0-140 ka). Since c. 1 Ma, the shelf has experienced limited subsidence and fluvial sediment input, producing a depositional regime characterised by extensive reworking of coastal and shelf sediments during glacio-eustatic sea-level fluctuations. It appears that only one complete fifth-order (c. 100 000 yr) depositional sequence is preserved beneath the inner shelf, the late Pleistocene Waihi Sequence, suggesting any earlier Quaternary sequences were mainly cannibalised into successively younger sequences. The predominantly Holocene-age Whangamata Sequence is also evident in seismic data and modern coastal deposits, and represents an incomplete depositional sequence in its early stages of formation. A prominent aspect of the sequence stratigraphy off parts of the east Coromandel coast is the presence of forced regressive deposits (FRDs) within the regressive systems tract (RST) of the late Pleistocene Waihi Sequence. The FRDs are interpreted to represent regressive barrier-shoreface sands that were sourced from erosion and onshore reworking of underlying Pleistocene sediments during the period of slow falling sea level from isotope stages 5 to 2 (c. 112-18 ka). The RST is volumetrically the most significant depositional component of the Waihi Sequence; the regressive deposits form a 15-20 m thick, sharp-based, tabular seismic unit that downsteps and progrades continuously across the inner shelf. The sequence boundary for the Waihi Sequence is placed at the most prominent, regionally correlative, and chronostratigraphically significant surface, namely an erosional unconformity characterised in many areas by large incised valleys that was generated above the RST. This unconformity is interpreted as a surface of maximum subaerial erosion generated during the last glacial lowstand (c. 18 ka). Although the base of the RST is associated with a prominent regressive surface of erosion, this is not used as the sequence boundary as it is highly diachronous and difficult to identify and correlate where FRDs are not developed. The previous highstand deposits are limited to subaerial barrier deposits preserved behind several modern Holocene barriers along the coast, while the transgressive systems tract is preserved locally as incised-valley fill deposits beneath the regressive surface of erosion at the base of the RST. Many documented late Pleistocene RSTs have been actively sourced from fluvial systems feeding the shelf and building basinward-thickening, often stacked wedges of FRDs, for which the name allochthonous FRDs is suggested. The Waihi Sequence RST is unusual in that it appears to have been sourced predominantly from reworking of underlying shelf sediments, and thus represents an autochthonous FRD. Autochthonous FRDs are also present on the Forster-Tuncurry shelf in southeast Australia, and may be a common feature in other shelf settings with low subsidence and low sediment supply rates, provided shelf gradients are not too steep, and an underlying source of unconsolidated shelf sediments is available to source FRDs. The preservation potential of such autochthonous FRDs in ancient deposits is probably low given that they are likely to be cannibalised during subsequent sea-level falls

On the Asymptotic Behaviour of Cosmological Models in Scalar-Tensor Theories of Gravity

We study the qualitative properties of cosmological models in scalar-tensor theories of gravity by exploiting the formal equivalence of these theories with general relativity minimally coupled to a scalar field under a conformal transformation and field redefinition. In particular, we investigate the asymptotic behaviour of spatially homogeneous cosmological models in a class of scalar-tensor theories which are conformally equivalent to general relativistic Bianchi cosmologies with a scalar field and an exponential potential whose qualitative features have been studied previously. Particular attention is focussed on those scalar-tensor theory cosmological models, which are shown to be self-similar, that correspond to general relativistic models that play an important r\^{o}le in describing the asymptotic behaviour of more general models (e.g., those cosmological models that act as early-time and late-time attractors).Comment: 22 pages, submitted to Phys Rev

Boson Stars in General Scalar-Tensor Gravitation: Equilibrium Configurations

We study equilibrium configurations of boson stars in the framework of general scalar-tensor theories of gravitation. We analyse several possible couplings, with acceptable weak field limit and, when known, nucleosynthesis bounds, in order to work in the cosmologically more realistic cases of this kind of theories. We found that for general scalar-tensor gravitation, the range of masses boson stars might have is comparable with the general relativistic case. We also analyse the possible formation of boson stars along different eras of cosmic evolution, allowing for the effective gravitational constant far out form the star to deviate from its current value. In these cases, we found that the boson stars masses are sensitive to this kind of variations, within a typical few percent. We also study cases in which the coupling is implicitly defined, through the dependence on the radial coordinate, allowing it to have significant variations in the radius of the structure.Comment: 19 pages in latex, 3 figures -postscript- may be sent via e-mail upon reques

Detectability of gravitational wave events by spherical resonant-mass antennas

We have calculated signal-to-noise ratios for eight spherical resonant-mass antennas interacting with gravitational radiation from inspiralling and coalescing binary neutron stars and from the dynamical and secular bar-mode instability of a rapidly rotating star. We find that by using technology that could be available in the next several years, spherical antennas can detect neutron star inspiral and coalescence at a distance of 15 Mpc and the dynamical bar-mode instability at a distance of 2 Mpc.Comment: 39 pages, 4 EPS Figures, some additional SNRs for secular instabilities, some changes to LIGO SNRs, Appendix added on the asymptotic expansion of energy sensitivity, corrected supernova rates. Results available at http://www.physics.umd.edu/rgroups/gen_rel_exp/snr.html Submitted to Phys. Rev.