Investigation of Structural Dynamics of Enzymes and Protonation States of Substrates Using Computational Tools.

This review discusses the use of molecular modeling tools, together with existing experimental findings, to provide a complete atomic-level description of enzyme dynamics and function. We focus on functionally relevant conformational dynamics of enzymes and the protonation states of substrates. The conformational fluctuations of enzymes usually play a crucial role in substrate recognition and catalysis. Protein dynamics can be altered by a tiny change in a molecular system such as different protonation states of various intermediates or by a significant perturbation such as a ligand association. Here we review recent advances in applying atomistic molecular dynamics (MD) simulations to investigate allosteric and network regulation of tryptophan synthase (TRPS) and protonation states of its intermediates and catalysis. In addition, we review studies using quantum mechanics/molecular mechanics (QM/MM) methods to investigate the protonation states of catalytic residues of β-Ketoacyl ACP synthase I (KasA). We also discuss modeling of large-scale protein motions for HIV-1 protease with coarse-grained Brownian dynamics (BD) simulations

Scaling Properties of Ge-SixGe1-x Core-Shell Nanowire Field Effect Transistors

We demonstrate the fabrication of high-performance Ge-SixGe1-x core-shell nanowire field-effect transistors with highly doped source and drain, and systematically investigate their scaling properties. Highly doped source and drain regions are realized by low energy boron implantation, which enables efficient carrier injection with a contact resistance much lower than the nanowire resistance. We extract key device parameters, such as intrinsic channel resistance, carrier mobility, effective channel length, and external contact resistance, as well as benchmark the device switching speed and ON/OFF current ratio.Comment: 5 pages, 4 figures. IEEE Transactions on Electron Devices (in press

Short Report: One-on-one consultation on protocol development and statistics analysis in health sciences postgraduate students

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A hybrid finite element approach to modeling sound radiation from circular and rectangular ducts

This is the post-print version of the Article - Copyright @ 2012 Acoustical Society of AmericaA numerical model based on a hybrid finite element method is developed that seeks to join sound pressure fields in interior and exterior regions. The hybrid method is applied to the analysis of sound radiation from open pipes, or ducts, and uses mode matching to couple a finite element discretization of the region surrounding the open end of the duct to wave based modal expansions for adjoining interior and exterior regions. The hybrid method facilitates the analysis of ducts of arbitrary but uniform cross section as well the study of conical flanges and here a modal expansion based on spherical harmonics is applied. Predictions are benchmarked against analytic solutions for the limiting cases of flanged and unflanged circular ducts and excellent agreement between the two methods is observed. Predictions are also presented for flanged and unflanged rectangular ducts, and because the hybrid method retains the sparse banded and symmetric matrices of the traditional finite element method, it is shown that predictions can be obtained within an acceptable time frame even for a three dimensional problem.This study is supported by the U.K. Engineering and Physical Sciences Research Council (EPSRC)

Outstanding Issues in Solar Dynamo Theory

The magnetic activity of the Sun, as manifested in the sunspot cycle, originates deep within its convection zone through a dynamo mechanism which involves non-trivial interactions between the plasma and magnetic field in the solar interior. Recent advances in magnetohydrodynamic dynamo theory have led us closer towards a better understanding of the physics of the solar magnetic cycle. In conjunction, helioseismic observations of large-scale flows in the solar interior has now made it possible to constrain some of the parameters used in models of the solar cycle. In the first part of this review, I briefly describe this current state of understanding of the solar cycle. In the second part, I highlight some of the outstanding issues in solar dynamo theory related to the the nature of the dynamo $\alpha$-effect, magnetic buoyancy and the origin of Maunder-like minima in activity. I also discuss how poor constraints on key physical processes such as turbulent diffusion, meridional circulation and turbulent flux pumping confuse the relative roles of these vis-a-vis magnetic flux transport. I argue that unless some of these issues are addressed, no model of the solar cycle can claim to be ``the standard model'', nor can any predictions from such models be trusted; in other words, we are still not there yet.Comment: To appear in "Magnetic Coupling between the Interior and the Atmosphere of the Sun", eds. S.S. Hasan and R.J. Rutten, Astrophysics and Space Science Proceedings, Springer-Verlag, Heidelberg, Berlin, 200

Applicability of self-consistent mean-field theory

Within the constrained Hartree-Fock (CHF) theory, an analytic condition is derived to estimate whether a concept of the self-consistent mean field is realized or not in level repulsive region. The derived condition states that an iterative calculation of CHF equation does not converge when the quantum fluctuations coming from two-body residual interaction and quadrupole deformation become larger than a single-particle energy difference between two avoided crossing orbits. By means of the numerical calculation, it is shown that the analytic condition works well for a realistic case.Comment: 11 pages, 8 figure

Terminal spacecraft rendezvous and capture with LASSO model predictive control

The recently investigated $\ell_{\mathrm{asso}}$ model predictive control (MPC) is applied to the terminal phase of a spacecraft rendezvous and capture mission. The interaction between the cost function and the treatment of minimum impulse bit (MIB) is also investigated. The propellant consumption with $\ell_{\mathrm{asso}}$ MPC for the considered scenario is noticeably less than with a conventional quadratic cost and control actions are sparser in time. Propellant consumption and sparsity are competitive with those achieved using a zone-based $\ell_1$ cost function, whilst requiring fewer decision variables in the optimisation problem than the latter. The $\ell_{\mathrm{asso}}$ MPC is demonstrated to meet tighter specifications on control precision, and also avoids the risk of undesirable behaviours often associated with pure $\ell_1$ stage costs.This work was supported by Engineering and Physical Sciences Research Council Grants EP/G030308/1 and EP/G066477/1.This is an Author's Accepted Manuscript of an article published in {International Journal of Control}, first published online on 20 Aug 2013 [copyright Taylor & Francis], available online at: http://www.tandfonline.com/10.1080/00207179.2013.78960

Linking dwarf galaxies to halo building blocks with the most metal-poor star in Sculptor

Current cosmological models indicate that the Milky Way's stellar halo was assembled from many smaller systems. Based on the apparent absence of the most metal-poor stars in present-day dwarf galaxies, recent studies claimed that the true Galactic building blocks must have been vastly different from the surviving dwarfs. The discovery of an extremely iron-poor star (S1020549) in the Sculptor dwarf galaxy based on a medium-resolution spectrum cast some doubt on this conclusion. However, verification of the iron-deficiency and measurements of additional elements, such as the alpha-element Mg, are mandatory for demonstrating that the same type of stars produced the metals found in dwarf galaxies and the Galactic halo. Only then can dwarf galaxy stars be conclusively linked to early stellar halo assembly. Here we report high-resolution spectroscopic abundances for 11 elements in S1020549, confirming the iron abundance of less than 1/4000th that of the Sun, and showing that the overall abundance pattern mirrors that seen in low-metallicity halo stars, including the alpha-elements. Such chemical similarity indicates that the systems destroyed to form the halo billions of years ago were not fundamentally different from the progenitors of present-day dwarfs, and suggests that the early chemical enrichment of all galaxies may be nearly identical.Comment: 16 pages, including 2 figures. Accepted for publication in Nature. It is embargoed for discussion in the press until formal publication in Natur

The long QT syndromes: genetic basis and clinical implications

AbstractIt is becoming clear that mutations in the KVLQT1, human “ether-a-go-go” related gene, cardiac voltage-dependent sodium channel gene, minK and MiRP1 genes, respectively, are responsible for the LQT1, LQT2, LQT3, LQT5 and LQT6 variants of the Romano-Ward syndrome, characterized by autosomal dominant transmission and no deafness. The much rarer Jervell-Lange-Nielsen syndrome (with marked QT prolongation and sensorineural deafness) arises when a child inherits mutant KVLQT1 or minK alleles from both parents. In addition, some families are not linked to the known genetic loci. Cardiac voltage-dependent sodium channel gene encodes the cardiac sodium channel, and long QT syndrome (LQTS) mutations prolong action potentials by increasing inward plateau sodium current. The other mutations cause a decrease in net repolarizing current by reducing potassium currents through “dominant negative” or “loss of function” mechanisms. Polymorphic ventricular tachycardia (torsade de pointes) is thought to be initiated by early after- depolarizations in the Purkinje system and maintained by reentry in the myocardium. Clinical presentations vary with the specific gene affected and the specific mutation. Nevertheless, patients with identical mutations can also present differently, and some patients with LQTS mutations may have no manifest baseline phenotype. The question of whether the latter situation is one of high risk for administration of QT prolonging drugs or during myocardial ischemia is under active investigation. More generally, the identification of LQTS genes has provided tremendous new insights for our understanding of normal cardiac electrophysiology and its perturbation in a wide range of conditions associated with sudden death. It seems likely that the approach of applying information from the genetics of uncommon congenital syndromes to the study of common acquired diseases will be an increasingly important one in the next millennium