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

Stochastic Vehicle Routing with Recourse

We study the classic Vehicle Routing Problem in the setting of stochastic optimization with recourse. StochVRP is a two-stage optimization problem, where demand is satisfied using two routes: fixed and recourse. The fixed route is computed using only a demand distribution. Then after observing the demand instantiations, a recourse route is computed -- but costs here become more expensive by a factor lambda. We present an O(log^2 n log(n lambda))-approximation algorithm for this stochastic routing problem, under arbitrary distributions. The main idea in this result is relating StochVRP to a special case of submodular orienteering, called knapsack rank-function orienteering. We also give a better approximation ratio for knapsack rank-function orienteering than what follows from prior work. Finally, we provide a Unique Games Conjecture based omega(1) hardness of approximation for StochVRP, even on star-like metrics on which our algorithm achieves a logarithmic approximation.Comment: 20 Pages, 1 figure Revision corrects the statement and proof of Theorem 1.

Self-trapping transition for nonlinear impurities embedded in a Cayley tree

The self-trapping transition due to a single and a dimer nonlinear impurity embedded in a Cayley tree is studied. In particular, the effect of a perfectly nonlinear Cayley tree is considered. A sharp self-trapping transition is observed in each case. It is also observed that the transition is much sharper compared to the case of one-dimensional lattices. For each system, the critical values of $\chi$ for the self-trapping transitions are found to obey a power-law behavior as a function of the connectivity $K$ of the Cayley tree.Comment: 6 pages, 7 fig

Intentional burns - A form of gender based violence in Nepal

We truly appreciate your important commentary regarding intentional burns in Nepal. Our study, while the first countrywide population based study on burns in Nepal, has several limitations

Processing of aluminum-graphite particulate metal matrix composites by advanced shear technology

Copyright @ 2009 ASM International. This paper was published in Journal of Materials Engineering and Performance 18(9) and is made available as an electronic reprint with the permission of ASM International. One print or electronic copy may be made for personal use only. Systematic or multiple reproduction, distribution to multiple locations via electronic or other means, duplications of any material in this paper for a fee or for commercial purposes, or modification of the content of this paper are prohibited.To extend the possibilities of using aluminum/graphite composites as structural materials, a novel process is developed. The conventional methods often produce agglomerated structures exhibiting lower strength and ductility. To overcome the cohesive force of the agglomerates, a melt conditioned high-pressure die casting (MC-HPDC) process innovatively adapts the well-established, high-shear dispersive mixing action of a twin screw mechanism. The distribution of particles and properties of composites are quantitatively evaluated. The adopted rheo process significantly improved the distribution of the reinforcement in the matrix with a strong interfacial bond between the two. A good combination of improved ultimate tensile strength (UTS) and tensile elongation (e) is obtained compared with composites produced by conventional processes.EPSR

Four Zero Texture Fermion Mass Matrices in SO(10) GUT

We attempt the integration of the phenomenologically successful four zero texture of fermion mass matrices with the renormalizable SO(10) GUT. The resulting scenario is found to be highly predictive. Firstly, we examine the phenomenological implications of a class of the lepton mass matrices with parallel texture structures and obtain interesting constraints on the parameters of the charged lepton and the neutrino mass matrices. We combine these phenomenological constraints with the constraints obtained from SO(10) GUT to reduce the number of the free parameters and to further constrain the allowed ranges of the free parameters. The solar/atmospheric mixing angles obtained in this analysis are in fairly good agreement with the data.Comment: 14 pages, 3 figures, 1 tabl

Glassy Phase Transition and Stability in Black Holes

Black hole thermodynamics, confined to the semi-classical regime, cannot address the thermodynamic stability of a black hole in flat space. Here we show that inclusion of correction beyond the semi-classical approximation makes a black hole thermodynamically stable. This stability is reached through a phase transition. By using Ehrenfest's scheme we further prove that this is a glassy phase transition with a Prigogine-Defay ratio close to 3. This value is well placed within the desired bound (2 to 5) for a glassy phase transition. Thus our analysis indicates a very close connection between the phase transition phenomena of a black hole and glass forming systems. Finally, we discuss the robustness of our results by considering different normalisations for the correction term.Comment: v3, minor changes over v2, references added, LaTeX-2e, 18 pages, 3 ps figures, to appear in Eour. Phys. Jour.

B_s --> mu+ mu- decay in the R-parity violating minimal supergravity

We study B_s --> mu+ mu- in the context of the R-parity violating minimal supergravity in the high tan beta regime. We find that the lowest value of the branching ratio can go well below the present LHCb sensitivity and hence B_s --> mu+ mu- can even be invisible to the LHC. We also find that the present upper bound on Br(B_s --> mu+ mu-) puts strong constraint on the minimal supergravity parameter space. The constraints become more severe if the upper bound is close to its standard model prediction.Comment: 18 pages, 10 figures; version to be published in European Physical Journal

Classes of exact Einstein-Maxwell solutions

We find new classes of exact solutions to the Einstein-Maxwell system of equations for a charged sphere with a particular choice of the electric field intensity and one of the gravitational potentials. The condition of pressure isotropy is reduced to a linear, second order differential equation which can be solved in general. Consequently we can find exact solutions to the Einstein-Maxwell field equations corresponding to a static spherically symmetric gravitational potential in terms of hypergeometric functions. It is possible to find exact solutions which can be written explicitly in terms of elementary functions, namely polynomials and product of polynomials and algebraic functions. Uncharged solutions are regainable with our choice of electric field intensity; in particular we generate the Einstein universe for particular parameter values.Comment: 16 pages, To appear in Gen. Relativ. Gravi

Search for DCC in 158A GeV Pb+Pb Collisions

A detailed analysis of the phase space distributions of charged particles and photons have been carried out using two independent methods. The results indicate the presence of nonstatistical fluctuations in localized regions of phase space.Comment: Talk at the PANIC99 Conference, June 9-16, 199