Propensity to form amyloid fibrils is encoded as excitations in the free energy landscape of monomeric proteins

Protein aggregation, linked to many of diseases, is initiated when monomers access rogue conformations that are poised to form amyloid fibrils. We show, using simulations of src SH3 domain, that mechanical force enhances the population of the aggregation prone ($N^*$) states, which are rarely populated under force free native conditions, but are encoded in the spectrum of native fluctuations. The folding phase diagrams of SH3 as a function of denaturant concentration ($[C]$), mechanical force ($f$), and temperature exhibit an apparent two-state behavior, without revealing the presence of the elusive $N^*$ states. Interestingly, the phase boundaries separating the folded and unfolded states at all [C] and $f$ fall on a master curve, which can can be quantitatively described using an analogy to superconductors in a magnetic field. The free energy profiles as a function of the molecular extension ($R$), which are accessible in pulling experiments, ($R$), reveal the presence of a native-like $N^*$ with a disordered solvent-exposed amino terminal $\beta$-strand. The structure of the $N^*$ state is identical to that found in Fyn SH3 by NMR dispersion experiments. We show that the time scale for fibril formation can be estimated from the population of the $N^*$ state, determined by the free energy gap separating the native structure and the $N^*$ state, a finding that can be used to assess fibril forming tendencies of proteins. The structures of the $N^*$ state are used to show that oligomer formation and likely route to fibrils occur by a domain-swap mechanism in SH3 domain.Comment: 12 pages, 8 figures, 9 supplementary figures (on 5 more pages), 2 supplementary movies (on youtube

Impact ionization fronts in Si diodes: Numerical evidence of superfast propagation due to nonlocalized preionization

We present numerical evidence of a novel propagation mode for superfast impact ionization fronts in high-voltage Si $p^+$-$n$-$n^+$ structures. In nonlinear dynamics terms, this mode corresponds to a pulled front propagating into an unstable state in the regime of nonlocalized initial conditions. Before the front starts to travel, field-ehanced emission of electrons from deep-level impurities preionizes initially depleted $n$ base creating spatially nonuniform free carriers profile. Impact ionization takes place in the whole high-field region. We find two ionizing fronts that propagate in opposite directions with velocities up to 10 times higher than the saturated drift velocity.Comment: 3 pages, 4 figure

Determination of Maintaining Time of Temperature Traces of Aerosol Droplet Water Flows During Motion in a Flame

To develop fire fighting technologies, the temperatures of combustible products were measured after passing an aerosol droplet flow of water through the flames (with monitored temperatures). It was applied the aerosol flows with droplets of sizes less than 100 [mu]m, 100-200 [mu]m, and 200-300 [mu]m. Investigations were conducted at a temperature of combustible products from 500 K to 900 K. Temperatures of gases in droplet flow traces and maintaining times of relatively low temperatures in these areas (it can be considered as temperature trace) were defined. It was obtained the satisfactory agreement of experimental results and numerical simulation data

The orbital poles of Milky Way satellite galaxies: a rotationally supported disc-of-satellites

Available proper motion measurements of Milky Way (MW) satellite galaxies are used to calculate their orbital poles and projected uncertainties. These are compared to a set of recent cold dark-matter (CDM) simulations, tailored specifically to solve the MW satellite problem. We show that the CDM satellite orbital poles are fully consistent with being drawn from a random distribution, while the MW satellite orbital poles indicate that the disc-of-satellites of the Milky Way is rotationally supported. Furthermore, the bootstrapping analysis of the spatial distribution of theoretical CDM satellites also shows that they are consistent with being randomly drawn. The theoretical CDM satellite population thus shows a significantly different orbital and spatial distribution than the MW satellites, most probably indicating that the majority of the latter are of tidal origin rather than being DM dominated sub-structures. A statistic is presented that can be used to test a possible correlation of satellite galaxy orbits with their spatial distribution.Comment: Accepted for publication in Ap