First passage times and asymmetry of DNA translocation

Motivated by experiments in which single-stranded DNA with a short hairpin loop at one end undergoes unforced diffusion through a narrow pore, we study the first passage times for a particle, executing one-dimensional brownian motion in an asymmetric sawtooth potential, to exit one of the boundaries. We consider the first passage times for the case of classical diffusion, characterized by a mean-square displacement of the form $\sim t$, and for the case of anomalous diffusion or subdiffusion, characterized by a mean-square displacement of the form $\sim t^{\gamma}$ with $0<\gamma<1$. In the context of classical diffusion, we obtain an expression for the mean first passage time and show that this quantity changes when the direction of the sawtooth is reversed or, equivalently, when the reflecting and absorbing boundaries are exchanged. We discuss at which numbers of `teeth' $N$ (or number of DNA nucleotides) and at which heights of the sawtooth potential this difference becomes significant. For large $N$, it is well known that the mean first passage time scales as $N^2$. In the context of subdiffusion, the mean first passage time does not exist. Therefore we obtain instead the distribution of first passage times in the limit of long times. We show that the prefactor in the power relation for this distribution is simply the expression for the mean first passage time in classical diffusion. We also describe a hypothetical experiment to calculate the average of the first passage times for a fraction of passage events that each end within some time $t^*$. We show that this average first passage time scales as $N^{2/\gamma}$ in subdiffusion.Comment: 10 pages, 4 figures We incorporated reviewers' suggestions from Physical Review E. We reformulated a few paragraphs in the introduction and further clarified the issue of the (a)symmetry of passage times. In the results section, we re-expressed the results in a form that manifest the important features. We also added a few references concerning anomalous diffusion. The look (but not the content) of figure 1 was also change

Investigation of passive flow control techniques to enhance the stall characteristics of a microlight aircraft

This report investigates the enhancement of aerodynamic stall characteristics of a Skyranger microlight aircraft by the use of passive flow control techniques, namely vortex generators and turbulators. Each flow control device is designed and scaled to application conditions. Force balance measurements and surface oil flow visualisation are carried out on a half-model of the microlight to further investigate the nature of the flow on the aircraft with and without the flow control devices. The results indicate a clear advantage to the use of turbulators compared with vortex generators. Turbulators increased the maximum lift coefficient by 2.8%, delayed the onset of stall by increasing the critical angle by 17.6% and reduced the drag penalty at both lower (pre-stall) and higher angles of attack by 8% compared to vortex generators. With vortex generators applied, the results indicated a delayed stall with an increase in the critical angle by 2% and a reduced drag penalty at higher angles of attack

Development of Parkinsonism following exposure to aripiprazole: two case reports

which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Introduction: Aripiprazole is a novel atypical neuroleptic used in the treatment of psychosis. A few recent studies have demonstrated an association between the use of aripiprazole and an exacerbation of Parkinsonism, although this relationship is poorly defined. To our knowledge, this is the first case series describing an onset of Parkinsonism in patients without prior history of Parkinson’s diseas

Energetic changes caused by antigenic module insertion in a virus-like particle revealed by experiment and molecular dynamics simulations

The success of recombinant virus-like particles (VLPs) for human papillomavirus and hepatitis B demonstrates the potential of VLPs as safe and efficacious vaccines. With new modular designs emerging, the effects of antigen module insertion on the self-assembly and structural integrity of VLPs should be clarified so as to better enabling improved design. Previous work has revealed insights into the molecular energetics of a VLP subunit, capsomere, comparing energetics within various solution conditions known to drive or inhibit self-assembly. In the present study, molecular dynamics (MD) simulations coupled with the molecular mechanics-Poisson-Boltzmann surface area (MM-PBSA) method were performed to examine the molecular interactions and energetics in a modular capsomere of a murine polyomavirus (MPV) VLP designed to protect against influenza. Insertion of an influenza antigenic module is found to lower the binding energy within the capsomere, and a more active state is observed in Assembly Buffer as compared with that in Stabilization Buffer, which has been experimentally validated through measurements using differential scanning calorimetry. Further in-depth analysis based on free-energy decomposition indicates that destabilized binding can be attributed to electrostatic interaction induced by the chosen antigen module. These results provide molecular insights into the conformational stability of capsomeres and their abilities to be exploited for antigen presentation, and are expected to be beneficial for the biomolecular engineering of VLP vaccines.Lin Zhang, Ronghong Tang, Shu Bai, Natalie K. Connors, Linda H.L. Lua, Yap P. Chuan, Anton P.J. Middelberg, Yan Su

Abundance of unknots in various models of polymer loops

A veritable zoo of different knots is seen in the ensemble of looped polymer chains, whether created computationally or observed in vitro. At short loop lengths, the spectrum of knots is dominated by the trivial knot (unknot). The fractional abundance of this topological state in the ensemble of all conformations of the loop of $N$ segments follows a decaying exponential form, $\sim \exp (-N/N_0)$, where $N_0$ marks the crossover from a mostly unknotted (ie topologically simple) to a mostly knotted (ie topologically complex) ensemble. In the present work we use computational simulation to look closer into the variation of $N_0$ for a variety of polymer models. Among models examined, $N_0$ is smallest (about 240) for the model with all segments of the same length, it is somewhat larger (305) for Gaussian distributed segments, and can be very large (up to many thousands) when the segment length distribution has a fat power law tail.Comment: 13 pages, 6 color figure

Residence Time Statistics for Normal and Fractional Diffusion in a Force Field

We investigate statistics of occupation times for an over-damped Brownian particle in an external force field. A backward Fokker-Planck equation introduced by Majumdar and Comtet describing the distribution of occupation times is solved. The solution gives a general relation between occupation time statistics and probability currents which are found from solutions of the corresponding problem of first passage time. This general relationship between occupation times and first passage times, is valid for normal Markovian diffusion and for non-Markovian sub-diffusion, the latter modeled using the fractional Fokker-Planck equation. For binding potential fields we find in the long time limit ergodic behavior for normal diffusion, while for the fractional framework weak ergodicity breaking is found, in agreement with previous results of Bel and Barkai on the continuous time random walk on a lattice. For non-binding potential rich physical behaviors are obtained, and classification of occupation time statistics is made possible according to whether or not the underlying random walk is recurrent and the averaged first return time to the origin is finite. Our work establishes a link between fractional calculus and ergodicity breaking.Comment: 12 page

The Energy Landscape, Folding Pathways and the Kinetics of a Knotted Protein

The folding pathway and rate coefficients of the folding of a knotted protein are calculated for a potential energy function with minimal energetic frustration. A kinetic transition network is constructed using the discrete path sampling approach, and the resulting potential energy surface is visualized by constructing disconnectivity graphs. Owing to topological constraints, the low-lying portion of the landscape consists of three distinct regions, corresponding to the native knotted state and to configurations where either the N- or C-terminus is not yet folded into the knot. The fastest folding pathways from denatured states exhibit early formation of the N-terminus portion of the knot and a rate-determining step where the C-terminus is incorporated. The low-lying minima with the N-terminus knotted and the C-terminus free therefore constitute an off-pathway intermediate for this model. The insertion of both the N- and C-termini into the knot occur late in the folding process, creating large energy barriers that are the rate limiting steps in the folding process. When compared to other protein folding proteins of a similar length, this system folds over six orders of magnitude more slowly.Comment: 19 page

Cherry-stones-based activated carbons as potential adsorbents for CO2/CH4 separation: effect of the activation parameters

This is the accepted version of the following article: Álvarez-Gutiérrez, N., Victoria Gil, M., Rubiera, F. and Pevida, C. (2015), Cherry-stones-based activated carbons as potential adsorbents for CO2/CH4 separation: effect of the activation parameters. Greenhouse Gas Sci Technol, 5: 812–825. doi: 10.1002/ghg.1534, which has been published in final form at http://dx.doi.org/10.1002/ghg.1534A low-cost biomass, cherry stones (CS), was used as a carbon precursor to synthesize two activated carbons to be used for CO2/CH4 separation. Single-step activation with two activating agents, carbon dioxide and steam, was used. The activation conditions that maximize the CO2 adsorption capacity by the adsorbents at 25 ºC and atmospheric pressure were determined by response surface methodology (RSM). The optimum values were 885 ºC and 12% of solid yield when activating with carbon dioxide, but 850 ºC and 15.3% of solid yield when activating with steam. Heating rate did not show a significant effect on the CO2 uptake. CO2 adsorption capacity values up to 11.45 and 10.56 wt.% were achieved under such conditions using carbon dioxide and steam as activating agents, respectively. Carbon dioxide activation promoted the development of microporosity, whereas both micropores and mesopores were developed during steam activation. The CO2/CH4 separation performance at 3 bar of the optimum adsorbents indicated that both cherry-stones-based activated carbons could have great potential as CO2 adsorbents for CO2/CH4 separation. The adsorbent activated with carbon dioxide, CS-CO2, showed a slightly higher adsorption capacity, but the steam-activated sample, CS-H2O, had an enhanced selectivity to separate CO2 from CO2/CH4 binary mixtures.This work was carried out with financial support from the Spanish MINECO (Project ENE2011-23467), co-financed by the European Regional Development Fund (ERDF) and from the Gobierno del Principado de Asturias (PCTI-GRUPIN14-079)Peer reviewe

Secure referee selection for fair and responsive peer-to-peer gaming

Peer-to-Peer (P2P) architectures for Massively Multiplayer Online Games (MMOG) provide better scalability than Client/Server (C/S); however, they increase the possibility of cheating. Recently proposed P2P protocols use trusted referees that simulate/validate the game to provide security equivalent to C/S. When selecting referees from untrusted peers, selecting non-colluding referees becomes critical. Further, referees should be selected such that the range and length of delays to players is minimised (maximising game fairness and responsiveness). In this paper we formally define the referee selection problem and propose two secure referee selection algorithms, SRS-1 and SRS-2, to solve it. Both algorithms ensure the probability of corrupt referees controlling a zone/region is below a predefined limit, while attempting to maximise responsiveness and fairness. The trade-off between responsiveness and fairness is adjustable for both algorithms. Simulations of three different scenarios show the effectiveness of our algorithms