Real sequence effects on the search dynamics of transcription factors on DNA

Recent experiments show that transcription factors (TFs) indeed use the facilitated diffusion mechanism to locate their target sequences on DNA in living bacteria cells: TFs alternate between sliding motion along DNA and relocation events through the cytoplasm. From simulations and theoretical analysis we study the TF-sliding motion for a large section of the DNA-sequence of a common E. coli strain, based on the two-state TF-model with a fast-sliding search state and a recognition state enabling target detection. For the probability to detect the target before dissociating from DNA the TF-search times self-consistently depend heavily on whether or not an auxiliary operator (an accessible sequence similar to the main operator) is present in the genome section. Importantly, within our model the extent to which the interconversion rates between search and recognition states depend on the underlying nucleotide sequence is varied. A moderate dependence maximises the capability to distinguish between the main operator and similar sequences. Moreover, these auxiliary operators serve as starting points for DNA looping with the main operator, yielding a spectrum of target detection times spanning several orders of magnitude. Auxiliary operators are shown to act as funnels facilitating target detection by TFs.Comment: 26 pages, 7 figure

Fluctuation spectrum of quasispherical membranes with force-dipole activity

The fluctuation spectrum of a quasi-spherical vesicle with active membrane proteins is calculated. The activity of the proteins is modeled as the proteins pushing on their surroundings giving rise to non-local force distributions. Both the contributions from the thermal fluctuations of the active protein densities and the temporal noise in the individual active force distributions of the proteins are taken into account. The noise in the individual force distributions is found to become significant at short wavelengths.Comment: 9 pages, 2 figures, minor changes and addition

Effective surface motion on a reactive cylinder of particles that perform intermittent bulk diffusion

In many biological and small scale technological applications particles may transiently bind to a cylindrical surface. In between two binding events the particles diffuse in the bulk, thus producing an effective translation on the cylinder surface. We here derive the effective motion on the surface, allowing for additional diffusion on the cylinder surface itself. We find explicit solutions for the number of adsorbed particles at one given instant, the effective surface displacement, as well as the surface propagator. In particular sub- and superdiffusive regimes are found, as well as an effective stalling of diffusion visible as a plateau in the mean squared displacement. We also investigate the corresponding first passage and first return problems.Comment: 26 pages, 5 figure

Well-posedness of Hydrodynamics on the Moving Elastic Surface

The dynamics of a membrane is a coupled system comprising a moving elastic surface and an incompressible membrane fluid. We will consider a reduced elastic surface model, which involves the evolution equations of the moving surface, the dynamic equations of the two-dimensional fluid, and the incompressible equation, all of which operate within a curved geometry. In this paper, we prove the local existence and uniqueness of the solution to the reduced elastic surface model by reformulating the model into a new system in the isothermal coordinates. One major difficulty is that of constructing an appropriate iterative scheme such that the limit system is consistent with the original system.Comment: The introduction is rewritte

Subdiffusion and weak ergodicity breaking in the presence of a reactive boundary

We derive the boundary condition for a subdiffusive particle interacting with a reactive boundary with finite reaction rate. Molecular crowding conditions, that are found to cause subdiffusion of larger molecules in biological cells, are shown to effect long-tailed distributions with identical exponent for both the unbinding times from the boundary to the bulk and the rebinding times from the bulk. This causes a weak ergodicity breaking: typically, an individual particle either stays bound or remains in the bulk for very long times. We discuss why this may be beneficial for in vivo gene regulation by DNA-binding proteins, whose typical concentrations are nanomolarComment: 4 pages, 1 figure, REVTeX4, accepted to Phys Rev Lett, some typos correcte

Open String Fluctuations in AdS with and without Torsion

The equations of motion and boundary conditions for the fluctuations around a classical open string, in a curved space-time with torsion, are considered in compact and world-sheet covariant form. The rigidly rotating open strings in Anti de Sitter space with and without torsion are investigated in detail. By carefully analyzing the tangential fluctuations at the boundary, we show explicitly that the physical fluctuations (which at the boundary are combinations of normal and tangential fluctuations) are finite, even though the world-sheet is singular there. The divergent 2-curvature thus seems less dangerous than expected, in these cases. The general formalism can be straightforwardly used also to study the (bosonic part of the) fluctuations around the closed strings, recently considered in connection with the AdS/CFT duality, on AdS_5 \times S^5 and AdS_3 \times S^3 \times T^4.Comment: 19 pages, Late

Langevin formulation for single-file diffusion

We introduce a stochastic equation for the microscopic motion of a tagged particle in the single file model. This equation provides a compact representation of several of the system's properties such as Fluctuation-Dissipation and Linear Response relations, achieved by means of a diffusion noise approach. Most important, the proposed Langevin Equation reproduces quantitatively the \emph{three} temporal regimes and the corresponding time scales: ballistic, diffusive and subdiffusive.Comment: 9 pages, 5 figures, 1 table, to appear in Physical Review

Geometric description for the anatomy of the mitral valve: A review

The mitral valve is a complex anatomical structure whose physiological functioning relies on the biomechanical properties and structural integrity of its components. Their compromise can lead to mitral valve dysfunction, associated with morbidity and mortality. Therefore, a review on the morphometry of the mitral valve is crucial, more specifically on the importance of valve dimensions and shape for its function. This review initially provides a brief background on the anatomy and physiology of the mitral valve, followed by an analysis of the morphological information available. A characterisation of mathematical descriptions of several parts of the valve is performed and the impact of different dimensions and shape changes in disease is then outlined. Finally, a section regarding future directions and recommendations for the use of morphometric information in clinical analysis of the mitral valve is presented