The biological and structural characterization of Mycobacterium tuberculosis UvrA provides novel insights into its mechanism of action

Mycobacterium tuberculosis is an extremely well adapted intracellular human pathogen that is exposed to multiple DNA damaging chemical assaults originating from the host defence mechanisms. As a consequence, this bacterium is thought to possess highly efficient DNA repair machineries, the nucleotide excision repair (NER) system amongst these. Although NER is of central importance to DNA repair in M. tuberculosis, our understanding of the processes in this species is limited. The conserved UvrABC endonuclease represents the multi-enzymatic core in bacterial NER, where the UvrA ATPase provides the DNA lesion-sensing function. The herein reported genetic analysis demonstrates that M. tuberculosis UvrA is important for the repair of nitrosative and oxidative DNA damage. Moreover, our biochemical and structural characterization of recombinant M. tuberculosis UvrA contributes new insights into its mechanism of action. In particular, the structural investigation reveals an unprecedented conformation of the UvrB-binding domain that we propose to be of functional relevance. Taken together, our data suggest UvrA as a potential target for the development of novel anti-tubercular agents and provide a biochemical framework for the identification of small-molecule inhibitors interfering with the NER activity in M. tuberculosis.

A low power, process invariant keeper design for high speed dynamic logic circuits

A low power keeper circuit using the concept of rate sensing has been proposed. The proposed technique reduces the amount of short circuit power dissipation in the domino gate by 70% compared to the conventional keeper technique. Also the total power-delay product is 26% lower compared to the previously reported techniques. The process tracking capability of the design enables the domino gate to achieve uniform delay across different process corners. This reduces the amount of short circuit power dissipation that occurs in the cascaded domino gates by 90%. The use of the proposed technique in the read path of a register file reduces the energy requirement by 26% as compared to the other keeper techniques. The proposed technique has been prototyped in 130nm CMOS technology.

Size-dependent and strain rate effects in quantum dot nanostructures with molecular dynamic simulations

Size and strain rate effects are among several factors which play an important role in determining the response of nanostructures, such as their deformations, to the mechanical loadings. The mechanical deformations in nanostructure systems at finite temperatures are intrinsically dynamic processes. Most of the recent works in this context have been focused on nanowires [1, 2], but very little attention has been paid to such low dimensional nanostructures as quantum dots (QDs). In this contribution, molecular dynamics (MD) simulations with an embedded atom potential method(EAM) are carried out to analyse the size and strain rate effects in the silicon (Si) QDs, as an example. We consider various geometries of QDs such as spherical, cylindrical and cubic. We choose Si QDs as an example due to their major applications in solar cells and biosensing. The analysis has also been focused on the variation in the deformation mechanisms with the size and strain rate for Si QD embedded in a matrix of SiO2 [3] (other cases include SiN and SiC matrices).It is observed that the mechanical properties are the functions of the QD size, shape and strain rate as it is in the case for nanowires [2]. We also present the comparative study resulted from the application of different EAM potentials in particular, the Stillinger-Weber (SW) potential, the Tersoff potentials and the environment-dependent interatomic potential (EDIP) [1]. Finally, based on the stabilized structural properties we compute electronic bandstructures of our nanostructures using an envelope function approach and its finite element implementation.

Energy Reduction in SRAM using Dynamic Voltage and Frequency Management

This paper describes a dynamic voltage frequency control scheme for a 256 X 64 SRAM block for reducing the energy in active mode and stand-by mode. The DVFM control system monitors the external clock and changes the supply voltage and the body bias so as to achieve a significant reduction in energy. The behavioral model of the proposed DVFM control system algorithm is described and simulated in HDL using delay and energy parameters obtained through SPICE simulation. The frequency range dictated by an external controller is 100 MHz to I GHz. The supply voltage of the complete memory system is varied in steps of 50 mV over the range of 500 mV to IV. The threshold voltage range of operation is plusmn100 mV around the nominal value, achieving 83.4% energy reduction in the active mode and 86.7% in the stand-by mode. This paper also proposes a energy replica that is used in the energy monitor subsystem of the DVFM system.

Effects of phase inhomogeneity and boundary conditions on the dynamic response of SMA wire actuators

This paper reports the simulation results from the dynamic analysis of a Shape Memory Alloy (SMA) actuator. The emphasis is on understanding the dynamic behavior under various loading rates and boundary conditions, resulting in complex scenarios such as thermal and stress gradients. Also, due to the polycrystalline nature of SMA wires, presence of microstructural inhomogeneity is inevitable. Probing the effect of inhomogeneity on the dynamic behavior can facilitate the prediction of life and characteristics of SMA wire actuator under varieties of boundary and loading conditions. To study the effect of these factors, an initial boundary value problem of SMA wire is formulated. This is subsequently solved using finite element method. The dynamic response of the SMA wire actuator is analyzed under mechanical loading and results are reported. Effect of loading rate, micro-structural inhomogeneity and thermal boundary conditions on the dynamic response of SMA wire actuator is investigated and the simulation results are reported.

Dynamic matrix rank with partial lookahead

We consider the problem of maintaining information about the rank of a matrix $M$ under changes to its entries. For an $n \times n$ matrix $M$, we show an amortized upper bound of $O(n^{\omega-1})$ arithmetic operations per change for this problem, where $\omega < 2.376$ is the exponent for matrix multiplication, under the assumption that there is a {\em lookahead} of up to $\Theta(n)$ locations. That is, we know up to the next $\Theta(n)$ locations $(i_1,j_1),(i_2,j_2),\ldots,$ whose entries are going to change, in advance; however we do not know the new entries in these locations in advance. We get the new entries in these locations in a dynamic manner.

Revisiting the Mechanism of the Triosephosphate Isomerase Reaction: The Role of the Fully Conserved Glutamic Acid 97 Residue

An analysis of 503 available triosephosphate isomerase sequences revealed nine fully conserved residues. Of these, four residues-K12, H95, E97 and E165-are capable of proton transfer and are all arrayed around the dihydroxyacetone phosphate substrate in the three-dimensional structure. Specific roles have been assigned to the residues K12, H95 and E165, but the nature of the involvement of E97 has not been established. Kinetic and structural characterization is reported for the E97Q and E97D mutants of Plasmodium falciparum triosephosphate isomerase (Pf TIM). A 4000-fold reduction in k(cat) is observed for E97Q, whereas the E97D mutant shows a 100-fold reduction. The control mutant, E165A, which lacks the key catalytic base, shows an approximately 9000-fold drop in activity. The integrity of the overall fold and stability of the dimeric structure have been demonstrated by biophysical studies. Crystal structures of E97Q and E97D mutants have been determined at 2.0 angstrom resolution. In the case of the isosteric replacement of glutamic acid by glutamine in the E97Q mutant a large conformational change for the critical K12 side chain is observed, corresponding to a trans-to-gauche transition about the C gamma-C delta (chi(3)) bond. In the E97D mutant, the K12 side chain maintains the wild-type orientation, but the hydrogen bond between K12 and D97 is lost. The results are interpreted as a direct role for E97 in the catalytic proton transfer cycle. The proposed mechanism eliminates the need to invoke the formation of the energetically unfavourable imidazolate anion at H95, a key feature of the classical mechanism.

Modeling wrap faced reinforced soil retaining walls subjected to dynamic excitation

This paper describes some of the physical and numerical model tests of reinforced soil retaining walls subjected to dynamic excitation through uni-axial shaking tests. Models of retaining walls are constructed in a perspex box with geotextile reinforcement using the wrap around technique with dry sand backfill and instrumented with displacement sensors, accelerometers and soil pressure sensors. Numerical modelling of these shaking table tests is carried using FLAC. Numerical model is validated by comparing physical model results. Responses of wrap faced walls with different number of reinforcement layers are discussed from both the physical and numerical model tests. Results showed that the displacements are decreasing with the increase in number of reinforcement layers while acceleration amplifications are not affected significantly.

An ultra-stable Cu nanowire under thermo-mechanical loading: A molecular dynamic study

We report on the formation of a stable Body-Centered Heptahedral (BCH) crystalline nanobridge structure of diameter ~ 1nm under high strain rate tensile loading to a <100> Cu nanowire. Extensive Molecular Dynamics (MD) simulations are performed. Six different cross-sectional dimensions of Cu nanowires are analyzed, i.e. 0.3615 x 0.3615 nm2, 0.723 x 0.723 nm2, 1.0845 x 1.0845 nm2, 1.446 x 1.446 nm2, 1.8075 x 1.8075 nm2, and 2.169 x 2.169 nm2. The strain rates used in the present simulations are 1 x 109 s-1, 1 x 108 s-1, and 1 x 107 s-1. We have shown that the length of the nanobridge can be characterized by larger plastic strain. A large plastic deformation is an indication that the structure is highly stable. The BCH nanobridge structure also shows enhanced mechanical properties such as higher fracture toughness and higher failure strain. The effect of temperature, strain rate and size of the nanowire on the formation of BCH structure is also explained in details. We also show that the initial orientation of the nanowires play an important role on the formation of BCH crystalline structure. Results indicate that proper tailoring of temperature and strain rate during processing or in the device can lead to very long BCH nanobridge structure of Cu with enhanced mechanical properties, which may find potential application for nano-scale electronic circuits.

Fully Comprehensive Geometrically Non-Linear Dynamic Analysis of Multi-Body Beam Systems with Elastic Couplings

This paper is concerned with the dynamic analysis of flexible,non-linear multi-body beam systems. The focus is on problems where the strains within each elastic body (beam) remain small. Based on geometrically non-linear elasticity theory, the non-linear 3-D beam problem splits into either a linear or non-linear 2-D analysis of the beam cross-section and a non-linear 1-D analysis along the beam reference line. The splitting of the three-dimensional beam problem into two- and one-dimensional parts, called dimensional reduction,results in a tremendous savings of computational effort relative to the cost of three-dimensional finite element analysis,the only alternative for realistic beams. The analysis of beam-like structures made of laminated composite materials requires a much more complicated methodology. Hence, the analysis procedure based on Variational Asymptotic Method (VAM), a tool to carry out the dimensional reduction, is used here.The analysis methodology can be viewed as a 3-step procedure. First, the sectional properties of beams made of composite materials are determined either based on an asymptotic procedure that involves a 2-D finite element nonlinear analysis of the beam cross-section to capture trapeze effect or using strip-like beam analysis, starting from Classical Laminated Shell Theory (CLST). Second, the dynamic response of non-linear, flexible multi-body beam systems is simulated within the framework of energy-preserving and energy-decaying time integration schemes that provide unconditional stability for non-linear beam systems. Finally,local 3-D responses in the beams are recovered, based on the 1-D responses predicted in the second step. Numerical examples are presented and results from this analysis are compared with those available in the literature.

Geometrically Nonlinear Dynamics of Composite Four-Bar Mechanisms

This work intends to demonstrate the importance of geometrically nonlinear crosssectional analysis of certain composite beam-based four-bar mechanisms in predicting system dynamic characteristics. All component bars of the mechanism are made of fiber reinforced laminates and have thin rectangular cross-sections. They could, in general, be pre-twisted and/or possess initial curvature, either by design or by defect. They are linked to each other by means of revolute joints. We restrict ourselves to linear materials with small strains within each elastic body (beam). Each component of the mechanism is modeled as a beam based on geometrically nonlinear 3-D elasticity theory. The component problems are thus split into 2-D analyses of reference beam cross-sections and nonlinear 1-D analyses along the four beam reference curves. For thin rectangular cross-sections considered here, the 2-D cross-sectional nonlinearity is overwhelming. This can be perceived from the fact that such sections constitute a limiting case between thin-walled open and closed sections, thus inviting the nonlinear phenomena observed in both. The strong elastic couplings of anisotropic composite laminates complicate the model further. However, a powerful mathematical tool called the Variational Asymptotic Method (VAM) not only enables such a dimensional reduction, but also provides asymptotically correct analytical solutions to the nonlinear cross-sectional analysis. Such closed-form solutions are used here in conjunction with numerical techniques for the rest of the problem to predict multi-body dynamic responses, more quickly and accurately than would otherwise be possible. The analysis methodology can be viewed as a three-step procedure: First, the cross-sectional properties of each bar of the mechanism is determined analytically based on an asymptotic procedure, starting from Classical Laminated Shell Theory (CLST) and taking advantage of its thin strip geometry. Second, the dynamic response of the nonlinear, flexible fourbar mechanism is simulated by treating each bar as a 1-D beam, discretized using finite elements, and employing energy-preserving and -decaying time integration schemes for unconditional stability. Finally, local 3-D deformations and stresses in the entire system are recovered, based on the 1-D responses predicted in the previous step. With the model, tools and procedure in place, we shall attempt to identify and investigate a few problems where the cross-sectional nonlinearities are significant. This will be carried out by varying stacking sequences and material properties, and speculating on the dominating diagonal and coupling terms in the closed-form nonlinear beam stiffness matrix. Numerical examples will be presented and results from this analysis will be compared with those available in the literature, for linear cross-sectional analysis and isotropic materials as special cases.

Robustness Study of a Dynamic Inversion Control Law for a High Performance Aircraft

In the design of °ight control system modeling uncertainties in the form of param-eter variations is one of the major problems. It is even more critical for high performance aircrafts,since such aircrafts are purposefully designed unstable to enhance their performance (especially ma-neuverability). Hence the °ight control system needs to be quite e®ective in both assuring accurate tracking of pilot commands, while simultaneously assuring overall stability of the aircraft. In addi-tion, the control system must also be su±ciently robust to cater for possible parameter variations and inaccuracies . The primary aim of this paper is to carry out a robustness study of a dynamic inversion based nonlinear control design for a high performance aircraft, which has been developed recently [1].