Stochastic Ratchet Mechanisms for Replacement of Proteins Bound to DNA

Experiments indicate that unbinding rates of proteins from DNA can depend on the concentration of proteins in nearby solution. Here we present a theory of multi-step replacement of DNA-bound proteins by solution-phase proteins. For four different kinetic scenarios we calculate the depen- dence of protein unbinding and replacement rates on solution protein concentration. We find (1) strong effects of progressive 'rezipping' of the solution-phase protein onto DNA sites liberated by 'unzipping' of the originally bound protein; (2) that a model in which solution-phase proteins bind non-specifically to DNA can describe experiments on exchanges between the non specific DNA- binding proteins Fis-Fis and Fis-HU; (3) that a binding specific model describes experiments on the exchange of CueR proteins on specific binding sites.Comment: \`a paraitre en PHys. Rev. Lett. june 201

Physics-based large-signal sensitivity analysis of microwave circuits using technological parametric sensitivity from multidimensional semiconductor device models

The authors present an efficient approach to evaluate the large-signal (LS) parametric sensitivity of active semiconductor devices under quasi-periodic operation through accurate, multidimensional physics-based models. The proposed technique exploits efficient intermediate mathematical models to perform the link between physics-based analysis and circuit-oriented simulations, and only requires the evaluation of dc and ac small-signal (dc charge) sensitivities under general quasi-static conditions. To illustrate the technique, the authors discuss examples of sensitivity evaluation, statistical analysis, and doping profile optimization of an implanted MESFET to minimize intermodulation which makes use of LS parametric sensitivities under two-tone excitatio

Earthquake‐induced landslide scenarios for seismic microzonation. Application to the Accumoli area (Rieti, Italy)

Scenarios of earthquake-induced landslides are necessary for seismic microzonation (SM) studies since they must be integrated with the mapping of instability areas. The PARSIFAL (Probabilistic Approach to pRovide Scenarios of earthquake‐Induced slope FAiLures) approach provides extensive analyses, over tens to thousands of square kilometers, and is designed as a fully comprehensive methodology to output expected scenarios which depend on seismic input and saturation conditions. This allows to attribute a rating, in terms of severity level, to the landslide-prone slope areas in view of future engineering studies and designs. PARSIFAL takes into account first-time rock- and earth-slides as well as re-activations of existing landslides performing slope stability analyses of different failure mechanisms. The results consist of mapping earthquake-induced landslide scenarios in terms of exceedance probability of critical threshold values of co-seismic displacements (P[D≥Dc|a(t),ay]). PARSIFAL was applied in the framework of level 3 SM studies over the municipality area of Accumoli (Rieti, Italy), strongly struck by the 2016 seismic sequence of Central Apennines. The use of the PARSIFAL was tested for the first time to screen the Susceptibility Zones (ZSFR) from the Attention Zones (ZAFR) in the category of the unstable areas, according to the guidelines by Italian Civil Protection. The results obtained were in a GIS-based mapping representing the possibility for a landslide to be induced by an earthquake (with a return period of 475 years) in three different saturation scenarios (i.e. dry, average, full). Only 41% of the landslide-prone areas in the Municipality of Accumoli are existing events, while the remaining 59% is characterized by first-time earth- or rock-slides. In dry conditions, unstable conditions or P[D≥Dc|a(t),ay]>0 were for 54% of existing landslides, 17% of first-time rock-slides and 1% of first-time earth- slides. In full saturation conditions, the findings are much more severe since unstable conditions or P[D≥Dc|a(t),ay]>0 were found for 58% of the existing landslides and for more than 80% of first-time rock- and earth-slides. Moreover, comparison of the total area of the ZAFR versus ZSFR, resulted in PARSIFAL screening reducing of 22% of the mapped ZAFR

Surface plasmon resonance imaging for affinity-based biosensors

SPR imaging (SPRi) is at the forefront of optical label-free and real-time detection. It offers the possibility of monitoring hundreds of biological interactions simultaneously and from the binding profiles, allows the estimation of the kinetic parameters of the interactions between the immobilised probes and the ligands in solution. We review the current state of development of SPRi technology and its application including commercially available SPRi instruments. Attention is also given to surface chemistries for biochip functionalisation and suitable approaches to improve sensitivity

Thermodynamics of beta-amyloid fibril formation

Amyloid fibers are aggregates of proteins. They are built out of a peptide called $\beta$--amyloid (A$\beta$) containing between 41 and 43 residues, produced by the action of an enzyme which cleaves a much larger protein known as the Amyloid Precursor Protein (APP). X-ray diffraction experiments have shown that these fibrils are rich in $\beta$--structures, whereas the shape of the peptide displays an $\alpha$--helix structure within the APP in its biologically active conformation. A realistic model of fibril formation is developed based on the seventeen residues A$\beta$12--28 amyloid peptide, which has been shown to form fibrils structurally similar to those of the whole A$\beta$ peptide. With the help of physical arguments and in keeping with experimental findings, the A$\beta$12--28 monomer is assumed to be in four possible states (i.e., native helix conformation, $\beta$--hairpin, globular low--energy state and unfolded state). Making use of these monomeric states, oligomers (dimers, tertramers and octamers) were constructed. With the help of short, detailed Molecular Dynamics (MD) calculations of the three monomers and of a variety of oligomers, energies for these structures were obtained. Making use of these results within the framework of a simple yet realistic model to describe the entropic terms associated with the variety of amyloid conformations, a phase diagram can be calculated of the whole many--body system, leading to a thermodynamical picture in overall agreement with the experimental findings. In particular, the existence of micellar metastable states seem to be a key issue to determine the thermodynamical properties of the system

Understanding the determinants of stability and folding of small globular proteins from their energetics

The results of minimal model calculations suggest that the stability and the kinetic accessibility of the native state of small globular proteins are controlled by few "hot" sites. By mean of molecular dynamics simulations around the native conformation, which simulate the protein and the surrounding solvent at full--atom level, we generate an energetic map of the equilibrium state of the protein and simplify it with an Eigenvalue decomposition. The components of the Eigenvector associated with the lowest Eigenvalue indicate which are the "hot" sites responsible for the stability and for the fast folding of the protein. Comparison of these predictions with the results of mutatgenesis experiments, performed for five small proteins, provide an excellent agreement

Fine frequency shift of sigle vortex entrance and exit in superconducting loops

The heat capacity $C_{p}$ of an array of independent aluminum rings has been measured under an external magnetic field $\vec{H}$ using highly sensitive ac-calorimetry based on a silicon membrane sensor. Each superconducting vortex entrance induces a phase transition and a heat capacity jump and hence $C_{p}$ oscillates with $\vec{H}$. This oscillatory and non-stationary behaviour measured versus the magnetic field has been studied using the Wigner-Ville distribution (a time-frequency representation). It is found that the periodicity of the heat capacity oscillations varies significantly with the magnetic field; the evolution of the period also depends on the sweeping direction of the field. This can be attributed to a different behavior between expulsion and penetration of vortices into the rings. A variation of more than 15% of the periodicity of the heat capacity jumps is observed as the magnetic field is varied. A description of this phenomenon is given using an analytical solution of the Ginzburg-Landau equations of superconductivity

Model adaptation enriched with an anisotropic mesh spacing for nonlinear equations: application to environmental and CFD problems

Goal of this paper is to suitably combine a model with an anisotropic mesh adaptation for the numerical simulation of nonlinear advection-diffusion-reaction systems and incompressible flows in ecological and environmental applications. Using the reduced-basis method terminology, the proposed approach leads to a noticeable computational saving of the online phase with respect to the resolution of the reference model on nonadapted grids. The search of a suitable adapted model/mesh pair is to be meant, instead, in an offline fashion