KCNK5 is Functionally Down-Regulated Upon Long-Term Hypotonicity in Ehrlich Ascites Tumor Cells

Background/Aims: Regulatory volume decrease (RVD) in response to acute cell swelling is well described and KCNK5 (also known as TASK-2 or K2P5.1) has been shown to be the volume sensitive K+ channel in Ehrlich cells. Very little is, on the other hand, known about the effects of long-term hypotonicity on expression and function of KCNK5, thus we have investigated the effect of long-term hypotonicity (24h - 48h) on KCNK5 in Ehrlich cells on the mRNA, protein and physiological levels. Methods: Physiological effects of long-term hypotonicity were measured using patch-clamp and Coulter counter techniques. Expression patterns of KCNK5 on mRNA and protein levels were established using real-time qPCR and western blotting respectively. Results: The maximum swelling-activated current through KCNK5 was significantly decreased upon 48h of hypotonicity and likewise the RVD response was significantly impaired after both 24 and 48h of hypotonic stimulation. No significant differences in the KCNK5 mRNA expression patterns between control and stimulated cells were observed, but a significant decrease in the KCNK5 protein level 48h after stimulation was found. Conclusion: The data suggest that the strong physiological impairment of KCNK5 in Ehrlich cells after long-term hypotonic stimulation is predominantly due to down-regulation of the KCNK5 protein synthesis

Stability transitions for axisymmetric relative equilibria of Euclidean symmetric Hamiltonian systems

In the presence of noncompact symmetry, the stability of relative equilibria under momentum-preserving perturbations does not generally imply robust stability under momentum-changing perturbations. For axisymmetric relative equilibria of Hamiltonian systems with Euclidean symmetry, we investigate different mechanisms of stability: stability by energy-momentum confinement, KAM, and Nekhoroshev stability, and we explain the transitions between these. We apply our results to the Kirchhoff model for the motion of an axisymmetric underwater vehicle, and we numerically study dissipation induced instability of KAM stable relative equilibria for this system.Comment: Minor revisions. Typographical errors correcte

Geometric variational problems of statistical mechanics and of combinatorics

We present the geometric solutions of the various extremal problems of statistical mechanics and combinatorics. Together with the Wulff construction, which predicts the shape of the crystals, we discuss the construction which exhibits the shape of a typical Young diagram and of a typical skyscraper.Comment: 10 page

Critical and Non-Critical Einstein-Weyl Supergravity

We construct N=1 supersymmetrisations of some recently-proposed theories of critical gravity, conformal gravity, and extensions of critical gravity in four dimensions. The total action consists of the sum of three separately off-shell supersymmetric actions containing Einstein gravity, a cosmological term and the square of the Weyl tensor. For generic choices of the coefficients for these terms, the excitations of the resulting theory around an AdS_4 background describe massive spin-2 and massless spin-2 modes coming from the metric; massive spin-1 modes coming from a vector field in the theory; and massless and massive spin-3/2 modes (with two unequal masses) coming from the gravitino. These assemble into a massless and a massive N=1 spin-2 multiplet. In critical supergravity, the coefficients are tuned so that the spin-2 mode in the massive multiplet becomes massless. In the supersymmetrised extensions of critical gravity, the coefficients are chosen so that the massive modes lie in a "window" of lowest energies E_0 such that these ghostlike fields can be truncated by imposing appropriate boundary conditions at infinity, thus leaving just positive-norm massless supergravity modes.Comment: 29 page

Bayes and health care research.

Bayes’ rule shows how one might rationally change one’s beliefs in the light of evidence. It is the foundation of a statistical method called Bayesianism. In health care research, Bayesianism has its advocates but the dominant statistical method is frequentism. There are at least two important philosophical differences between these methods. First, Bayesianism takes a subjectivist view of probability (i.e. that probability scores are statements of subjective belief, not objective fact) whilst frequentism takes an objectivist view. Second, Bayesianism is explicitly inductive (i.e. it shows how we may induce views about the world based on partial data from it) whereas frequentism is at least compatible with non-inductive views of scientific method, particularly the critical realism of Popper. Popper and others detail significant problems with induction. Frequentism’s apparent ability to avoid these, plus its ability to give a seemingly more scientific and objective take on probability, lies behind its philosophical appeal to health care researchers. However, there are also significant problems with frequentism, particularly its inability to assign probability scores to single events. Popper thus proposed an alternative objectivist view of probability, called propensity theory, which he allies to a theory of corroboration; but this too has significant problems, in particular, it may not successfully avoid induction. If this is so then Bayesianism might be philosophically the strongest of the statistical approaches. The article sets out a number of its philosophical and methodological attractions. Finally, it outlines a way in which critical realism and Bayesianism might work together. </p

Theoretical study of the thermal behavior of free and alumina-supported Fe-C nanoparticles

The thermal behavior of free and alumina-supported iron-carbon nanoparticles is investigated via molecular dynamics simulations, in which the effect of the substrate is treated with a simple Morse potential fitted to ab initio data. We observe that the presence of the substrate raises the melting temperature of medium and large $Fe_{1-x}C_x$ nanoparticles ($x$ = 0-0.16, $N$ = 80-1000, non- magic numbers) by 40-60 K; it also plays an important role in defining the ground state of smaller Fe nanoparticles ($N$ = 50-80). The main focus of our study is the investigation of Fe-C phase diagrams as a function of the nanoparticle size. We find that as the cluster size decreases in the 1.1-1.6-nm-diameter range the eutectic point shifts significantly not only toward lower temperatures, as expected from the Gibbs-Thomson law, but also toward lower concentrations of C. The strong dependence of the maximum C solubility on the Fe-C cluster size may have important implications for the catalytic growth of carbon nanotubes by chemical vapor deposition.Comment: 13 pages, 11 figures, higher quality figures can be seen in article 9 at http://alpha.mems.duke.edu/wahyu

Monte Carlo study of the evaporation/condensation transition on different Ising lattices

In 2002 Biskup et al. [Europhys. Lett. 60, 21 (2002)] sketched a rigorous proof for the behavior of the 2D Ising lattice gas, at a finite volume and a fixed excess \delta M of particles (spins) above the ambient gas density (spontaneous magnetisation). By identifying a dimensionless parameter \Delta (\delta M) and a universal constant \Delta_c, they showed in the limit of large system sizes that for \Delta < \Delta_c the excess is absorbed in the background (``evaporated'' system), while for \Delta > \Delta_c a droplet of the dense phase occurs (``condensed'' system). To check the applicability of the analytical results to much smaller, practically accessible system sizes, we performed several Monte Carlo simulations for the 2D Ising model with nearest-neighbour couplings on a square lattice at fixed magnetisation M. Thereby, we measured the largest minority droplet, corresponding to the condensed phase, at various system sizes (L=40, >..., 640). With analytic values for for the spontaneous magnetisation m_0, the susceptibility \chi and the Wulff interfacial free energy density \tau_W for the infinite system, we were able to determine \lambda numerically in very good agreement with the theoretical prediction. Furthermore, we did simulations for the spin-1/2 Ising model on a triangular lattice and with next-nearest-neighbour couplings on a square lattice. Again, finding a very good agreement with the analytic formula, we demonstrate the universal aspects of the theory with respect to the underlying lattice. For the case of the next-nearest-neighbour model, where \tau_W is unknown analytically, we present different methods to obtain it numerically by fitting to the distribution of the magnetisation density P(m).Comment: 14 pages, 17 figures, 1 tabl

Colligative properties of solutions: I. Fixed concentrations

Using the formalism of rigorous statistical mechanics, we study the phenomena of phase separation and freezing-point depression upon freezing of solutions. Specifically, we devise an Ising-based model of a solvent-solute system and show that, in the ensemble with a fixed amount of solute, a macroscopic phase separation occurs in an interval of values of the chemical potential of the solvent. The boundaries of the phase separation domain in the phase diagram are characterized and shown to asymptotically agree with the formulas used in heuristic analyses of freezing point depression. The limit of infinitesimal concentrations is described in a subsequent paper.Comment: 28 pages, 1 fig; see also math-ph/0407035 (both to appear in JSP

The clock genes Period 2 and Cryptochrome 2 differentially balance bone formation

Background: Clock genes and their protein products regulate circadian rhythms in mammals but have also been implicated in various physiological processes, including bone formation. Osteoblasts build new mineralized bone whereas osteoclasts degrade it thereby balancing bone formation. To evaluate the contribution of clock components in this process, we investigated mice mutant in clock genes for a bone volume phenotype. Methodology/Principal Findings: We found that Per2Brdm1 mutant mice as well as mice lacking Cry2-/- displayed significantly increased bone volume at 12 weeks of age, when bone turnover is high. Per2Brdm1 mutant mice showed alterations in parameters specific for osteoblasts whereas mice lacking Cry2-/- displayed changes in osteoclast specific parameters. Interestingly, inactivation of both Per2 and Cry2 genes leads to normal bone volume as observed in wild type animals. Importantly, osteoclast parameters affected due to the lack of Cry2, remained at the level seen in the Cry2-/- mutants despite the simultaneous inactivation of Per2. Conclusions/Significance: This indicates that Cry2 and Per2 affect distinct pathways in the regulation of bone volume with Cry2 influencing mostly the osteoclastic cellular component of bone and Per2 acting on osteoblast parameters