Spatial arrangement of LD motif-interacting residues on focal adhesion targeting domain of Focal Adhesion Kinase determine domain-motif interaction affinity and specificity

Background: Leucine rich Aspartate motifs (LD motifs) are molecular recognition motifs on Paxillin that recognize LD-motif binding domains (LDBD) of a number of focal adhesion proteins in order to carry out downstream signaling and actin cytoskeleton remodeling. In this study, we identified structural features within LDBDs that influence their binding affinity with Paxillin LD motifs. Methods: Various point mutants of focal adhesion targeting (FAT) domain of Focal Adhesion Kinase (FAK) were created by moving a key Lysine residue two and three helical turns in order to match the unique conformations as observed in LDBDs of two other focal adhesion proteins, Vinculin and CCM3. Results: This led to identify a mutant of FAT domain of FAK, named as FAT(NV) (Asn992 of FAT domain was replaced by Val), with remarkable high affinity for LD1 (Kd = 1.5 µM vs no-binding with wild type) and LD2 peptides (Kd = 7.2 µM vs 63 µM with wild type). Consistently, the focal adhesions of MCF7 cells expressing FAK(NV) were highly stable (turnover rate = 1.25 × 10-5 µm2/s) as compared to wild type FAK transfected cells (turnover rate = 1.5 × 10-3 µm2/s). Conclusions: We observed that the relative disposition of key LD binding amino-acids at LDBD surface, hydrophobic burial of long Leucine side chains of LD-motifs and complementarity of charged surfaces are the key factors determining the binding affinities of LD motifs with LDBDs. General significance: Our study will help in protein engineering of FAT domain of FAK by modulating FAK-LD motif interactions which have implications in cellular focal adhesions and cell migration

Simulating EGFR-ERK signaling control by scaffold proteins KSR and MP1 reveals differential Ligand-Sensitivity Co-Regulated by CBL-CIN85 and Endophilin

10.1371/journal.pone.0022933PLoS ONE68

Machine learning-based investigation of the association between CMEs and filaments

YesIn this work we study the association between eruptive filaments/prominences and coronal mass ejections (CMEs) using machine learning-based algorithms that analyse the solar data available between January 1996 and December 2001. The Support Vector Machine (SVM) learning algorithm is used for the purpose of knowledge extraction from the association results. The aim is to identify patterns of associations that can be represented using SVM learning rules for the subsequent use in near real-time and reliable CME prediction systems. Timing and location data in the NGDC filament catalogue and the SOHO/LASCO CME catalogue are processed to associate filaments with CMEs. In the previous studies which classified CMEs into gradual and impulsive CMEs, the associations were refined based on CME speed and acceleration. Then the associated pairs were refined manually to increase the accuracy of the training dataset. In the current study, a data- mining system has been created to process and associate filament and CME data, which are arranged in numerical training vectors. Then the data are fed to SVMs to extract the embedded knowledge and provide the learning rules that could have the potential, in the future, to provide automated predictions of CMEs. The features representing the event time (average of the start and end times), duration, type and extent of the filaments are extracted from all the associated and not-associated filaments and converted to a numerical format that is suitable for SVM use. Several validation and verification methods are used on the extracted dataset to determine if CMEs can be predicted solely and efficiently based on the associated filaments. More than 14000 experiments are carried out to optimise the SVM and determine the input features that provide the best performance

Spin Measurements in Cascade Decays at the LHC

We systematically study the possibility of determining the spin of new particles after their discovery at the LHC. We concentrate on angular correlations in cascade decays. Motivated by constraints of electroweak precision tests and the potential of providing a Cold Dark Matter candidate, we focus on scenarios of new physics in which some discrete symmetry guarantees the existence of stable neutral particles which escape the detector. More specifically, we compare supersymmetry with another generic scenario in which new physics particles have the same spin as their Standard Model partners. A survey of possibilities of observing spin correlations in a broad range of decay channels is carried out, with interesting ones identified. Rather than confining ourselves to one "collider friendly" benchmark point (such as SPS1a), we describe the parameter region in which any particular decay channel is effective. We conduct a more detailed study of chargino's spin determination in the decay channel $\tilde{q}\to q + \tilde{C}^\pm \to q + W^\pm + LSP$. A scan over the chargino and neutralino masses is performed. We find that as long as the spectrum is not too degenerate the prospects for spin determination in this channel are rather good.Comment: 36 pages, references added, 1 figure modifie

Nonlinear force-free magnetic field extrapolations: comparison of the Grad-Rubin and Wheatland-Sturrock-Roumeliotis algorithm

We compare the performance of two alternative algorithms which aim to construct a force-free magnetic field given suitable boundary conditions. For this comparison, we have implemented both algorithms on the same finite element grid which uses Whitney forms to describe the fields within the grid cells. The additional use of conjugate gradient and multigrid iterations result in quite effective codes. The Grad-Rubin and Wheatland-Sturrock-Roumeliotis algorithms both perform well for the reconstruction of a known analytic force-free field. For more arbitrary boundary conditions the Wheatland-Sturrock-Roumeliotis approach has some difficulties because it requires overdetermined boundary information which may include inconsistencies. The Grad-Rubin code on the other hand loses convergence for strong current densities. For the example we have investigated, however, the maximum possible current density seems to be not far from the limit beyond which a force free field cannot exist anymore for a given normal magnetic field intensity on the boundary.Comment: 21 pages, 13 figure

An exact solution of the moving boundary problem for the relativistic plasma expansion in a dipole magnetic field

An exact analytic solution is obtained for a uniformly expanding, neutral, highly conducting plasma sphere in an ambient dipole magnetic field with an arbitrary orientation of the dipole moment in the space. Based on this solution the electrodynamical aspects related to the emission and transformation of energy have been considered. In order to highlight the effect of the orientation of the dipole moment in the space we compare our results obtained for parallel orientation with those for transversal orientation. The results obtained can be used to treat qualitatively experimental and simulation data, and several phenomena of astrophysical and laboratory significance.Comment: 7 pages, 2 figures. arXiv admin note: substantial text overlap with arXiv:physics/060323

Dirichlet sigma models and mean curvature flow

The mean curvature flow describes the parabolic deformation of embedded branes in Riemannian geometry driven by their extrinsic mean curvature vector, which is typically associated to surface tension forces. It is the gradient flow of the area functional, and, as such, it is naturally identified with the boundary renormalization group equation of Dirichlet sigma models away from conformality, to lowest order in perturbation theory. D-branes appear as fixed points of this flow having conformally invariant boundary conditions. Simple running solutions include the paper-clip and the hair-pin (or grim-reaper) models on the plane, as well as scaling solutions associated to rational (p, q) closed curves and the decay of two intersecting lines. Stability analysis is performed in several cases while searching for transitions among different brane configurations. The combination of Ricci with the mean curvature flow is examined in detail together with several explicit examples of deforming curves on curved backgrounds. Some general aspects of the mean curvature flow in higher dimensional ambient spaces are also discussed and obtain consistent truncations to lower dimensional systems. Selected physical applications are mentioned in the text, including tachyon condensation in open string theory and the resistive diffusion of force-free fields in magneto-hydrodynamics.Comment: 77 pages, 21 figure

A Nonlinear Force-Free Magnetic Field Approximation Suitable for Fast Forward-Fitting to Coronal Loops. I. Theory

We derive an analytical approximation of nonlinear force-free magnetic field solutions (NLFFF) that can efficiently be used for fast forward-fitting to solar magnetic data, constrained either by observed line-of-sight magnetograms and stereoscopically triangulated coronal loops, or by 3D vector-magnetograph data. The derived NLFFF solutions provide the magnetic field components $B_x({\bf x})$, $B_y({\bf x})$, $B_z({\bf x})$, the force-free parameter $\alpha({\bf x})$, the electric current density ${\bf j}({\bf x})$, and are accurate to second-order (of the nonlinear force-free $\alpha$-parameter). The explicit expressions of a force-free field can easily be applied to modeling or forward-fitting of many coronal phenomena.Comment: Solar Physics (in press), 26 pages, 11 figure

Coronal mass ejections as expanding force-free structures

We mode Solar coronal mass ejections (CMEs) as expanding force-fee magnetic structures and find the self-similar dynamics of configurations with spatially constant \alpha, where {\bf J} =\alpha {\bf B}, in spherical and cylindrical geometries, expanding spheromaks and expanding Lundquist fields correspondingly. The field structures remain force-free, under the conventional non-relativistic assumption that the dynamical effects of the inductive electric fields can be neglected. While keeping the internal magnetic field structure of the stationary solutions, expansion leads to complicated internal velocities and rotation, induced by inductive electric field. The structures depends only on overall radius R(t) and rate of expansion \dot{R}(t) measured at a given moment, and thus are applicable to arbitrary expansion laws. In case of cylindrical Lundquist fields, the flux conservation requires that both axial and radial expansion proceed with equal rates. In accordance with observations, the model predicts that the maximum magnetic field is reached before the spacecraft reaches the geometric center of a CME.Comment: 19 pages, 9 Figures, accepted by Solar Physic