Polymer Translocation Dynamics in the Quasi-Static Limit

Monte Carlo (MC) simulations are used to study the dynamics of polymer translocation through a nanopore in the limit where the translocation rate is sufficiently slow that the polymer maintains a state of conformational quasi-equilibrium. The system is modeled as a flexible hard-sphere chain that translocates through a cylindrical hole in a hard flat wall. In some calculations, the nanopore is connected at one end to a spherical cavity. Translocation times are measured directly using MC dynamics simulations. For sufficiently narrow pores, translocation is sufficiently slow that the mean translocation time scales with polymer length N according to \propto (N-N_p)^2, where N_p is the average number of monomers in the nanopore; this scaling is an indication of a quasi-static regime in which polymer-nanopore friction dominates. We use a multiple-histogram method to calculate the variation of the free energy with Q, a coordinate used to quantify the degree of translocation. The free energy functions are used with the Fokker-Planck formalism to calculate translocation time distributions in the quasi-static regime. These calculations also require a friction coefficient, characterized by a quantity N_{eff}, the effective number of monomers whose dynamics are affected by the confinement of the nanopore. This was determined by fixing the mean of the theoretical distribution to that of the distribution obtained from MC dynamics simulations. The theoretical distributions are in excellent quantitative agreement with the distributions obtained directly by the MC dynamics simulations for physically meaningful values of N_{eff}. The free energy functions for narrow-pore systems exhibit oscillations with an amplitude that is sensitive to the nanopore length. Generally, larger oscillation amplitudes correspond to longer translocation times.Comment: 13 pages, 13 figure

Mixing in density- and viscosity-stratified flows

The lock-exchange problem is used extensively to study the flow dynamics of density-driven flows, such as gravity currents, and as a canonical problem to mixing in stratified flows. Opposite halves of a domain are filled with two fluids of different densities and held in place by a lock-gate. Upon release, the density difference drives the flow causing the fluids to slosh back and forth. In many scenarios, density stratification will also impose a viscosity stratification (e.g., if there are suspended sediments or the two fluids are distinct). However, numerical models often neglect variable viscosity. This paper characterizes the effect of both density and viscosity stratification in the lock-exchange configuration. The governing Navier-Stokes equations are solved using direct numerical simulation. Three regimes are identified in terms of the viscosity ratio μ 2 / μ 1 = (1 + γ) between the dense and less dense fluids: when γ ≪ 1, the flow dynamics are similar to the equal-viscosity case; for intermediate values (γ ∼ 1), viscosity inhibits interface-scale mixing leading to a global reduction in mixing and enhanced transfer between potential and kinetic energy. Increasing the excess viscosity ratio further (γ ≫ 1) results in significant viscous dissipation. Although many gravity or turbidity current models assume constant viscosity, our results demonstrate that viscosity stratification can only be neglected when γ ≪ 1. The initial turbidity current composition could enhance its ability to become self-sustaining or accelerating at intermediate excess viscosity ratios. Currents with initially high excess viscosity ratio may be unable to dilute and propagate long distances because of the decreased mixing rates and increased dissipation

Pulse propagation in gravity currents

Real world gravity current flows rarely exist as a single discrete event, but are instead made up of multiple surges. This paper examines the propagation of surges as pulses in gravity currents. Using theoretical shallow-water modeling, we analyze the structure of pulsed flows created by the sequential release of two lock-boxes. The first release creates a gravity current, while the second creates a pulse that eventually propagates to the head of the first current. Two parameters determine the flow structure: the densimetric Froude number at the head of the current, Fr, and a dimensionless time between releases, tre. The shallow-water model enables the flow behavior to be mapped in (Fr, tre) space. Pulse speed depends on three critical characteristic curves: two that derive from the first release and correspond to a wavelike disturbance which reflects between the head of the current and the back of the lock-box and a third that originates from the second release and represents the region of the flow affected by the finite supply of source material. Pulses have non-negative acceleration until they intersect the third characteristic, after which they decelerate. Variations in pulse speed affect energy transfer and dissipation. Critically for lahars, landslides, and avalanches, pulsed flows may change from erosional to depositional, further affecting their dynamics. Gravity current hazard prediction models for such surge-prone flows may underpredict risk if they neglect internal flow dynamics

The role of spin-orbit coupling in the optical spectroscopy of atomic sodium isolated in solid xenon

Molecular dynamics calculations, based on the diatomics-in-molecules method, have been used to probe the manifestations of spin-orbit (SO) coupling in the experimental absorption bands of atomic sodium isolated in solid xenon. Inclusion of SO coupling of –320 cm−1 in spectral simulations of the 3p 2P 3s 2S transition leads to unequal band spacings which very closely match the asymmetrical bandshape observed for blue single vacancy (SV) site occupancy. This SO value, extracted in a previous MCD study, reveals the dramatic change in the effective SO coupling constant of the Na atom (from the gas phase value of +17 cm−1 ) in solid Xe when it is close to the 12 xenon atoms in the first surrounding sphere. In contrast, the symmetrical three-fold split band of the red tetra vacancy (TV) site in Na/Xe is not affected nearly as much by SO coupling. This reflects a greatly reduced “external heavy atom” effect when the 24 Xe atoms surrounding the Na atom in TV are located at greater distances. The contrasting behavior of sodium in the SV and TV sites suggests a strong dependence of the SO coupling strength on the Na–Xe distance

Social support moderates the relationship between stressors and task performance through self-efficacy

This study examined the relationship between social support and objective task performance in a field setting. A sample of 197 participants, mean age 23.13 years (SD 3.56) completed measures of stressors, social support, and self-efficacy prior to performance. Moderated hierarchical regression analysis revealed significant(p < .05) main effects for stressors (R2 = .12) and social support (ΔR2 = .14) in relation to performance, in the hypothesized directions. A significant interaction (ΔR2 = .06) suggested that social support moderated (buffered) the relationship between stressors and task performance. Moderated mediation analysis demonstrated that social support was associated with increases in self-efficacy, and self-efficacy was associated with enhanced performance, but that this effect was only salient at moderate to high levels of stressors

The structural basis for the specificity of pyridinylimidazole inhibitors of p38 MAP kinase

AbstractBackground: The p38 mitogen-activated protein (MAP) kinase regulates signal transduction in response to environmental stress. Pyridinylimidazole compounds are specific inhibitors of p38 MAP kinase that block the production of the cytokines interleukin-1 β and tumor necrosis factor α, and they are effective in animal models of arthritis, bone resorption and endotoxin shock. These compounds have been useful probes for studying the physiological functions of the p38-mediated MAP kinase pathway.Results: We report the crystal structure of a novel pyridinylimidazole compound complexed with p38 MAP kinase, and we demonstrate that this compound binds to the same site on the kinase as does ATP. Mutagenesis showed that a single residue difference between p38 MAP kinase and other MAP kinases is sufficient to confer selectivity among pyridinylimidazole compounds.Conclusions: Our results reveal how pyridinylimidazole compounds are potent and selective inhibitors of p38 MAP kinase but not other MAP kinases. It should now be possible to design other specific inhibitors of activated p38 MAP kinase using the structure of the nonphosphorylated enzyme

Стимулированное излучение молекулами тетрабензопарфина в низкотемпературных матрицах благородных газов

В работе представлены результаты спектральных исследований молекул тетрабензопорфина (Н2ТБП), внедренных в твердотельные матрицы благородных газов (Ar, Xe)

Blockade of T-cell activation by dithiocarbamates involves novel mechanisms of inhibition of nuclear factor of activated T cells.

Dithiocarbamates (DTCs) have recently been reported as powerful inhibitors of NF-kappaB activation in a number of cell types. Given the role of this transcription factor in the regulation of gene expression in the inflammatory response, NF-kappaB inhibitors have been suggested as potential therapeutic drugs for inflammatory diseases. We show here that DTCs inhibited both interleukin 2 (IL-2) synthesis and membrane expression of antigens which are induced during T-cell activation. This inhibition, which occurred with a parallel activation of c-Jun transactivating functions and expression, was reflected by transfection experiments at the IL-2 promoter level, and involved not only the inhibition of NF-kappaB-driven reporter activation but also that of nuclear factor of activated T cells (NFAT). Accordingly, electrophoretic mobility shift assays (EMSAs) indicated that pyrrolidine DTC (PDTC) prevented NF-kappaB, and NFAT DNA-binding activity in T cells stimulated with either phorbol myristate acetate plus ionophore or antibodies against the CD3-T-cell receptor complex and simultaneously activated the binding of AP-1. Furthermore, PDTC differentially targeted both NFATp and NFATc family members, inhibiting the transactivation functions of NFATp and mRNA induction of NFATc. Strikingly, Western blotting and immunocytochemical experiments indicated that PDTC promoted a transient and rapid shuttling of NFATp and NFATc, leading to their accelerated export from the nucleus of activated T cells. We propose that the activation of an NFAT kinase by PDTC could be responsible for the rapid shuttling of the NFAT, therefore transiently converting the sustained transactivation of this transcription factor that occurs during lymphocyte activation, and show that c-Jun NH2-terminal kinase (JNK) can act by directly phosphorylating NFATp. In addition, the combined inhibitory effects on NFAT and NF-KB support a potential use of DTCs as immunosuppressants