Nanomechanics combined with HDX reveals allosteric drug binding sites of CFTR NBD1.

Cystic fibrosis (CF) is a frequent genetic disease in Caucasians that is caused by the deletion of F508 (DF508) in the nucleotide binding domain 1 (NBD1) of the CF transmembrane conductance regulator (CFTR). The DF508 compromises the folding energetics of the NBD1, as well as the folding of three other CFTR domains. Combination of FDA approved corrector molecules can efficiently but incompletely rescue the DF508-CFTR folding and stability defect. Thus, new pharmacophores that would reinstate the wild-type-like conformational stability of the DF508-NBD1 would be highly beneficial. The most prominent molecule, 5-bromoindole-3-acetic acid (BIA) that can thermally stabilize the NBD1 has low potency and efficacy. To gain insights into the NBD1 (un)folding dynamics and BIA binding site localization, we combined molecular dynamics (MD) simulations, atomic force spectroscopy (AFM) and hydrogen- deuterium exchange (HDX) experiments. We found that the NBD1 a-subdomain with three adjacent strands from the b-subdomain plays an important role in early folding steps, when crucial non-native interactions are formed via residue F508. Our AFM and HDX experiments showed that BIA associates with this a-core region and increases the resistance of the DF508-NBD1 against mechanical unfolding, a phenomenon that could be exploited in future developments of folding correctors

Nonlinear integral equations for finite volume excited state energies of the O(3) and O(4) nonlinear sigma-models

We propose nonlinear integral equations for the finite volume one-particle energies in the O(3) and O(4) nonlinear sigma-models. The equations are written in terms of a finite number of components and are therefore easier to solve numerically than the infinite component excited state TBA equations proposed earlier. Results of numerical calculations based on the nonlinear integral equations and the excited state TBA equations agree within numerical precision.Comment: numerical results adde

Two New White Dwarfs With Variable Magnetic Balmer Emission Lines

We report the discovery of two apparently isolated stellar remnants that exhibit rotationally modulated magnetic Balmer emission, adding to the emerging DAHe class of white dwarf stars. While the previously discovered members of this class show Zeeman-split triplet emission features corresponding to single magnetic field strengths, these two new objects exhibit significant fluctuations in their apparent magnetic field strengths with variability phase. The Zeeman-split hydrogen emission lines in LP $705{-}64$ broaden from $9.4$ MG to $22.2$ MG over an apparent spin period of $72.629$ minutes. Similarly, WD J$143019.29{-}562358.33$ varies from $5.8$ MG to $8.9$ MG over its apparent $86.394$-minute rotation period. This brings the DAHe class of white dwarfs to at least five objects, all with effective temperatures within $500$ K of $8000$ K and masses ranging from $0.65{-}0.83\,M_{\odot}$.Comment: 7 pages, 3 figures. Accepted for publication in MNRA

Response of a catalytic reaction to periodic variation of the CO pressure: Increased CO_2 production and dynamic phase transition

We present a kinetic Monte Carlo study of the dynamical response of a Ziff-Gulari-Barshad model for CO oxidation with CO desorption to periodic variation of the CO presure. We use a square-wave periodic pressure variation with parameters that can be tuned to enhance the catalytic activity. We produce evidence that, below a critical value of the desorption rate, the driven system undergoes a dynamic phase transition between a CO_2 productive phase and a nonproductive one at a critical value of the period of the pressure oscillation. At the dynamic phase transition the period-averged CO_2 production rate is significantly increased and can be used as a dynamic order parameter. We perform a finite-size scaling analysis that indicates the existence of power-law singularities for the order parameter and its fluctuations, yielding estimated critical exponent ratios $\beta/\nu \approx 0.12$ and $\gamma/\nu \approx 1.77$. These exponent ratios, together with theoretical symmetry arguments and numerical data for the fourth-order cumulant associated with the transition, give reasonable support for the hypothesis that the observed nonequilibrium dynamic phase transition is in the same universality class as the two-dimensional equilibrium Ising model.Comment: 18 pages, 10 figures, accepted in Physical Review

Statistical analysis of plasma filaments in the island divertor of Wendelstein 7-X

Plasma filaments have been measured with alkali beam emission spectroscopy in the plasma edge, divertor island, and scrape-off layer of Wendelstein 7-X. Due to the high intensity of a 1–2 kHz plasma mode, a new, correlation based conditional averaging algorithm was used to search for filaments in the signals. With that method, effects of different magnetic configurations and density levels on filament properties are observed. In configurations where the islands are small and do not play an important role for the connection length topology, filaments behave similar to tokamaks. In contrast, in configurations with larger magnetic islands and more complex connection length profiles, filaments behave quite differently, for instance they may or may not appear in the inner side of the divertor island depending on the plasma parameters. Coupling between the filaments and lower frequency events are also showed. The role of filaments in the global and local particle transport is briefly discussed