Contractile Strength during Variable Heart Duration Is Species and Preload Dependent

We investigate the effect of beat-to-beat variability on cardiac contractility. Cardiac trabeculae were isolated from the right ventricle of rabbits and beagle dogs and stimulated to isometrically contract, alternating between fixed steady state versus variable interbeat intervals. Trabeculae were stimulated at physiologically relevant frequencies for each species (dog 1 and 4 Hz; rabbit 2 and 4 Hz) intercalating fixed periods with 40% variability. A subset of the trabeculae (at 90% of optimal length) was stretched prior to stimulation between 5 and 13% and stimulated at the same frequencies with a fixed versus 40% variation. Fixed rate response at the same base frequency was measured before and after each variable period and the average force reported. In canine preparations no change in force was observed as a result of the imposed variability in beat-to-beat duration. In the rabbit, we observed a nonsignificant decrease in force between fixed and variable pacing at both 2 and 4 Hz (n = 8) when 40% variability was introduced. When a 5% and 13% stretch was applied, the correlation coefficient sharply increased, indicating a more prominent impact of the prebeat duration on the following cycle with higher preload

Prospects for high-resolution microwave spectroscopy of methanol in a Stark-deflected molecular beam

Recently, the extremely sensitive torsion-rotation transitions in methanol have been used to set a tight constraint on a possible variation of the proton-to-electron mass ratio over cosmological time scales. In order to improve this constraint, laboratory data of increased accuracy will be required. Here, we explore the possibility for performing high-resolution spectroscopy on methanol in a Stark-deflected molecular beam. We have calculated the Stark shift of the lower rotational levels in the ground torsion-vibrational state of CH3OH and CD3OH molecules, and have used this to simulate trajectories through a typical molecular beam resonance setup. Furthermore, we have determined the efficiency of non-resonant multi-photon ionization of methanol molecules using a femtosecond laser pulse. The described setup is in principle suited to measure microwave transitions in CH3OH at an accuracy below 10^{-8}

Staurosporine Inhibits Frequency-Dependent Myofilament Desensitization in Intact Rabbit Cardiac Trabeculae

Myofilament calcium sensitivity decreases with frequency in intact healthy rabbit trabeculae and associates with Troponin I and Myosin light chain-2 phosphorylation. We here tested whether serine-threonine kinase activity is primarily responsible for this frequency-dependent modulations of myofilament calcium sensitivity. Right ventricular trabeculae were isolated from New Zealand White rabbit hearts and iontophoretically loaded with bis-fura-2. Twitch force-calcium relationships and steady state force-calcium relationships were measured at frequencies of 1 and 4 Hz at 37 °C. Staurosporine (100 nM), a nonspecific serine-threonine kinase inhibitor, or vehicle (DMSO) was included in the superfusion solution before and during the contractures. Staurosporine had no frequency-dependent effect on force development, kinetics, calcium transient amplitude, or rate of calcium transient decline. The shift in the pCa50 of the force-calcium relationship was significant from 6.05 ± 0.04 at 1 Hz versus 5.88 ± 0.06 at 4 Hz under control conditions (vehicle, P < 0.001) but not in presence of staurosporine (5.89 ± 0.08 at 1 Hz versus 5.94 ± 0.07 at 4 Hz, P = NS). Phosphoprotein analysis (Pro-Q Diamond stain) confirmed that staurosporine significantly blunted the frequency-dependent phosphorylation at Troponin I and Myosin light chain-2. We conclude that frequency-dependent modulation of calcium sensitivity is mediated through a kinase-specific effect involving phosphorylation of myofilament proteins

Percolation Threshold, Fisher Exponent, and Shortest Path Exponent for 4 and 5 Dimensions

We develop a method of constructing percolation clusters that allows us to build very large clusters using very little computer memory by limiting the maximum number of sites for which we maintain state information to a number of the order of the number of sites in the largest chemical shell of the cluster being created. The memory required to grow a cluster of mass s is of the order of $s^\theta$ bytes where $\theta$ ranges from 0.4 for 2-dimensional lattices to 0.5 for 6- (or higher)-dimensional lattices. We use this method to estimate $d_{\scriptsize min}$, the exponent relating the minimum path $\ell$ to the Euclidean distance r, for 4D and 5D hypercubic lattices. Analyzing both site and bond percolation, we find $d_{\scriptsize min}=1.607\pm 0.005$ (4D) and $d_{\scriptsize min}=1.812\pm 0.006$ (5D). In order to determine $d_{\scriptsize min}$ to high precision, and without bias, it was necessary to first find precise values for the percolation threshold, $p_c$: $p_c=0.196889\pm 0.000003$ (4D) and $p_c=0.14081\pm 0.00001$ (5D) for site and $p_c=0.160130\pm 0.000003$ (4D) and $p_c=0.118174\pm 0.000004$ (5D) for bond percolation. We also calculate the Fisher exponent, $\tau$, determined in the course of calculating the values of $p_c$: $\tau=2.313\pm 0.003$ (4D) and $\tau=2.412\pm 0.004$ (5D)

Ageing in bosonic particle-reaction models with long-range transport

Ageing in systems without detailed balance is studied in bosonic contact and pair-contact processes with Levy diffusion. In the ageing regime, the dynamical scaling of the two-time correlation function and two-time response function is found and analysed. Exact results for non-equilibrium exponents and scaling functions are derived. The behaviour of the fluctuation-dissipation ratio is analysed. A passage time from the quasi-stationary regime to the ageing regime is defined, in qualitative agreement with kinetic spherical models and p-spin spherical glasses.Comment: Latex2e, 24 pages, with 9 figures include

Ageing, dynamical scaling and its extensions in many-particle systems without detailed balance

Recent studies on the phenomenology of ageing in certain many-particle systems which are at a critical point of their non-equilibrium steady-states, are reviewed. Examples include the contact process, the parity-conserving branching-annihilating random walk, two exactly solvable particle-reaction models and kinetic growth models. While the generic scaling descriptions known from magnetic system can be taken over, some of the scaling relations between the ageing exponents are no longer valid. In particular, there is no obvious generalization of the universal limit fluctuation-dissipation ratio. The form of the scaling function of the two-time response function is compared with the prediction of the theory of local scale-invariance.Comment: Latex2e with IOP macros, 32 pages; extended discussion on contact process and new section on kinetic growth processe

Microbiome on the Bone-Anchored Hearing System: A Prospective Study

The bone-anchored hearing system (BAHS) has evolved to a common treatment option for various types of hearing revalidation. The BAHS consists of an implant in the skull that breeches the skin. Soft tissue reactions are a common complication associated with BAHS and are generally poorly understood. This study aims to investigate the influence of BAHS and associated skin reactions around the implant. A total of 45 patients were prospectively followed from implantation up to at least 1 year. Swabs were obtained at baseline, 12 weeks follow-up and during cases of inflammation (Holgers score ≥2). The microbiota was assessed using IS-proTM, a bacterial profiling method based on the interspace region between the 16S–23S rRNA genes. Detection of operational taxonomic units, the Shannon Diversity Index, sample similarity analyses and Partial Least Squares Discriminant Analysis (PLS-DA) were employed. Staphylococcus epidermidis, Streptococcus pneumoniae/mitis, Propionibacterium acnes, Staphylococcus capitis, Staphylococcus hominis, Bifidobacterium longum, Haemophilus parainfluenzae, Lactobacillus rhamnosus, Bordetella spp., Streptococcus sanguinis, Peptostreptococcus anaerobius, Staphylococcus aureus, Lactococcus lactis, Enterobacter cloacae, and Citrobacter koseri were the most commonly found bacterial species. S. pneumoniae/mitis was significantly more often observed after implantation, whereas P. acnes was significantly less observed after implantation compared with baseline. The relative abundance of S. epidermidis (17%) and S. aureus (19.4%) was the highest for the group of patients with inflammation. The Shannon Diversity Index was significantly increased after implantation compared with pre-surgical swabs for Firmicutes, Actinobacteria, Fusobacteria, Verrucomicrobia (FAFV), but not for other phyla. When combining all phyla, there was no significant increase in the Shannon Diversity Index. The diversity index was similar post-surgically for patients experiencing inflammation and for patients without inflammation. With a supervised classifier (PLS-DA), patients prone to inflammation could be identified at baseline with an accuracy of 91.7%. In addition, PLS-DA could classify post-surgical abutments as non-inflamed or inflamed with an accuracy of 97.7%. This study shows the potential of using IS-proTM to describe and quantify the microbiota associated with the percutaneous BAHS. Furthermore, the results indicate the possibility of an early identification of patients susceptible to adverse skin reaction following implantation. Both S. aureus and S. epidermidis should be considered as relevant bacteria for BAHS-associated inflammation