Diffusive spatio-temporal noise in a first-passage time model for intracellular calcium release

The intracellular release of calcium from the endoplasmic reticulum is controlled by ion channels. The resulting calcium signals exhibit a rich spatio-temporal signature, which originates at least partly from microscopic fluctuations. While stochasticity in the gating transition of ion channels has been incorporated into many models, the distribution of calcium is usually described by deterministic reaction-diffusion equations. Here we test the validity of the latter modeling approach by using two different models to calculate the frequency of localized calcium signals (calcium puffs) from clustered IP3 receptor channels. The complexity of the full calcium system is here limited to the basic opening mechanism of the ion channels and, in the mathematical reduction simplifies to the calculation of a first passage time. Two models are then studied: (i) a hybrid model, where channel gating is treated stochastically, while calcium concentration is deterministic and (ii) a fully stochastic model with noisy channel gating and Brownian calcium ion motion. The second model utilises the recently developed two-regime method [M. B. Flegg, S. J. Chapman, and R. Erban, “The two-regime method for optimizing stochastic reaction-diffusion simulations,” J. R. Soc., Interface9, 859–868 (Year: 2012)]10.1098/rsif.2011.0574 in order to simulate a large domain with precision required only near the Ca2+ absorbing channels. The expected time for a first channel opening that results in a calcium puff event is calculated. It is found that for a large diffusion constant, predictions of the interpuff time are significantly overestimated using the model (i) with a deterministic non-spatial calcium variable. It is thus demonstrated that the presence of diffusive noise in local concentrations of intracellular Ca2+ ions can substantially influence the occurrence of calcium signals. The presented approach and results may also be relevant for other cell-physiological first-passage time problems with small ligand concentration and high cooperativity

A biological sequence comparison algorithm using quantum computers

Genetic information is encoded in a linear sequence of nucleotides, represented by letters ranging from thousands to billions. Mutations refer to changes in the DNA or RNA nucleotide sequence. Thus, mutation detection is vital in all areas of biology and medicine. Careful monitoring of virulence-enhancing mutations is essential. However, an enormous amount of classical computing power is required to analyze genetic sequences of this size. Inspired by human perception of vision and pixel representation of images on quantum computers, we leverage these techniques to implement a pairwise sequence analysis. The methodology has a potential advantage over classical approaches and can be further applied to identify mutations and other modifications in genetic sequences. We present a method to display and analyze the similarity between two genome sequences on a quantum computer where a similarity score is calculated to determine the similarity between nucleotides.Comment: 14 pages, 8 figures, 3 tables New version: typo in figure 7 New version because of a missing information in affiliations in footer, page

Magnetic field generation in fully convective rotating spheres

Magnetohydrodynamic simulations of fully convective, rotating spheres with volume heating near the center and cooling at the surface are presented. The dynamo-generated magnetic field saturates at equipartition field strength near the surface. In the interior, the field is dominated by small-scale structures, but outside the sphere by the global scale. Azimuthal averages of the field reveal a large-scale field of smaller amplitude also inside the star. The internal angular velocity shows some tendency to be constant along cylinders and is ``anti-solar'' (fastest at the poles and slowest at the equator).Comment: 12 pages, 11 figures, 2 tables, to appear in the 10 Feb issue of Ap

The Accretion Rates and Spectral Energy Distributions of BL Lacertae Objects

We investigate the relationship between accretion rates and the spectral energy distributions (SEDs) of BL Lac objects, using a sample of objects for which published information on the host galaxies, emission-line luminosities, and peak frequencies and luminosities of their SEDs are available. The sample is composed of 43 BL Lac objects which have a relatively continuous distribution of peak frequencies. Under the assumption that the observed emission lines are photoionized by the central accretion disk, we use the line luminosities to estimate the accretion luminosities and hence accretion rates. We find that low frequency-peaked BL Lac objects (LBLs) span a wide range of accretion rates, whereas high frequency-peaked BL Lac objects (HBLs) cover a more restricted range of lower values. There appears to be a continuous distribution of accretion rates between the two subclasses of BL Lac objects. We find that the peak frequency of the SED, \pknu, correlates with the accretion rate, approximately with the form \pknu\propto \Lambda^{-3} in HBLs and \pknu \propto \Lambda^{-0.25} in LBLs, where $\Lambda \equiv L_{\rm lines}/c^2$. The peak luminosity of the SED is also correlated with $\Lambda$. These results suggest that the accretion rate influences the shape of the SED in BL Lac objects. They also support models which couple the jet and the accretion disk. We present a physical scenario to account for the empirical trends.Comment: 6 pages in emulateapj.sty, 3 figures 1 table. The Astrophysical Journal (in press

The role of Hall diffusion in the magnetically threaded thin accretion discs

We study role of the Hall diffusion in the magnetic star-disc interaction. In a simplified steady state configuration, the total torque is calculated in terms of the fastness parameter and a new term because of the Hall diffusion. We show the total torque reduces as the Hall term becomes more significant. Also, the critical fastness parameter (at which the total torque is zero) reduces because of the Hall diffusion.Comment: Accepted for publication in Astrophysics and Space Scienc

Preoperative and perioperative use of levosimendan in cardiac surgery: European expert opinion

In cardiac surgery, postoperative low cardiac output has been shown to correlate with increased rates of organ failure and mortality. Catecholamines have been the standard therapy for many years, although they carry substantial risk for adverse cardiac and systemic effects, and have been reported to be associated with increased mortality. On the other hand, the calcium sensitiser and potassium channel opener levosimendan has been shown to improve cardiac function with no imbalance in oxygen consumption, and to have protective effects in other organs. Numerous clinical trials have indicated favourable cardiac and non-cardiac effects of preoperative and perioperative administration of levosimendan. A panel of 27 experts from 18 countries has now reviewed the literature on the use of levosimendan in on-pump and off-pump coronary artery bypass grafting and in heart valve surgery. This panel discussed the published evidence in these various settings, and agreed to vote on a set of questions related to the cardioprotective effects of levosimendan when administered preoperatively, with the purpose of reaching a consensus on which patients could benefit from the preoperative use of levosimendan and in which kind of procedures, and at which doses and timing should levosimendan be administered. Here, we present a systematic review of the literature to report on the completed and ongoing studies on levosimendan, including the newly commenced LEVO-CTS phase III study (NCT02025621), and on the consensus reached on the recommendations proposed for the use of preoperative levosimendan

Intensivmedizinische Behandlung von Erwachsenen mit angeborenen Herzfehlern

Zusammenfassung: Dank Verbesserungen in der Herzchirurgie und der perioperativen Betreuung steigt die Anzahl der Erwachsenen mit einem angeborenen Herzfehler stetig. Die perioperative und intensivmedizinische Betreuung dieser Patienten stellt aufgrund der vielen verschiedenen Pathologien und chirurgischen Möglichkeiten sowie der komplexen Pathophysiologie eine Herausforderung dar. Viele Patienten entwickeln mit der Zeit Organdysfunktionen und viele von ihnen benötigen Folgeoperationen am Herzen sowie nichtkardiale Eingriffe im Erwachsenalter. Aufgrund der Komplexität sind diese Patienten in spezialisierten tertiären Krankenhäusern zu behandeln, die über ein disziplinenübergreifendes Fachwissen verfügen. Da dies in Notfällen nicht immer möglich sein wird, sind grundlegende Kenntnisse dieser Patientengruppe für in der Akutversorgung Tätige wichtig. In dieser Übersicht werden allgemeine Aspekte, wie pulmonale Hypertonie, Eisenmenger-Syndrom, Zyanose, Schwangerschaft und perioperative Betreuung, behandelt. Ein besonderes Augenmerk gilt dabei der intensivmedizinischen Versorgung von kritisch kranken Patienten mit angeborenen Herzfehler