Nonspecific transcription factor binding can reduce noise in the expression of downstream proteins.

Transcription factors (TFs) interact with a multitude of binding sites on DNA and partner proteins inside cells. We investigate how nonspecific binding/unbinding to such decoy binding sites affects the magnitude and time-scale of random fluctuations in TF copy numbers arising from stochastic gene expression. A stochastic model of TF gene expression, together with decoy site interactions is formulated. Distributions for the total (bound and unbound) and free (unbound) TF levels are derived by analytically solving the chemical master equation under physiologically relevant assumptions. Our results show that increasing the number of decoy binding sides considerably reduces stochasticity in free TF copy numbers. The TF autocorrelation function reveals that decoy sites can either enhance or shorten the time-scale of TF fluctuations depending on model parameters. To understand how noise in TF abundances propagates downstream, a TF target gene is included in the model. Intriguingly, we find that noise in the expression of the target gene decreases with increasing decoy sites for linear TF-target protein dose-responses, even in regimes where decoy sites enhance TF autocorrelation times. Moreover, counterintuitive noise transmissions arise for nonlinear dose-responses. In summary, our study highlights the critical role of molecular sequestration by decoy binding sites in regulating the stochastic dynamics of TFs and target proteins at the single-cell level.

First-principles conductance of nanoscale junctions from the polarizability of finite systems.

A method for the calculation of the conductance of nanoscale electrical junctions is extended to ab initio electronic structure methods that make use of the periodic supercell technique and applied to realistic models of metallic wires and break junctions of sodium and gold. The method is systematically controllable and convergeable and can be straightforwardly extended to include more complex processes and interactions. Important issues, about the order in which the thermodynamic and static (small field) limits are taken, are clarified, and characterized further through comparisons to model systems.

Stroboscopic wave-packet description of nonequilibrium many-electron problems.

We introduce the construction of an orthogonal wave-packet basis set, using the concept of stroboscopic time propagation, tailored to the efficient description of nonequilibrium extended electronic systems. Thanks to three desirable properties of this basis, significant insight is provided into nonequilibrium processes (both time-dependent and steady-state), and reliable physical estimates of various many-electron quantities such as density, current, and spin polarization can be obtained. Use of the wave-packet basis provides new results for time-dependent switching-on of the bias in quantum transport, and for current-induced spin accumulation at the edge of a 2D doped semiconductor caused by edge-induced spin-orbit interaction.