Modelling multiple disulphide loop containing polypeptides by random conformation generation. The test cases of α-conotoxin GI and edothelin I

A general procedure for arriving at 3-D models of disulphiderich olypeptide systems based on the covalent cross-link constraints has been developed. The procedure, which has been coded as a computer program, RANMOD, assigns a large number of random, permitted backbone conformations to the polypeptide and identifies stereochemically acceptable structures as plausible models based on strainless disulphide bridge modelling. Disulphide bond modelling is performed using the procedure MODIP developed earlier, in connection with the choice of suitable sites where disulphide bonds could be engineered in proteins (Sowdhamini,R., Srinivasan,N., Shoichet,B., Santi,D.V., Ramakrishnan,C. and Balaram,P. (1989) Protein Engng, 3, 95-103). The method RANMOD has been tested on small disulphide loops and the structures compared against preferred backbone conformations derived from an analysis of putative disulphide subdatabase and model calculations. RANMOD has been applied to disulphiderich peptides and found to give rise to several stereochemically acceptable structures. The results obtained on the modelling of two test cases, a-conotoxin GI and endothelin I, are presented. Available NMR data suggest that such small systems exhibit conformational heterogeneity in solution. Hence, this approach for obtaining several distinct models is particularly attractive for the study of conformational excursions.

Non-Abelian monopoles break color. I. Classical mechanics

Monopoles which are sources of non-Abelian magnetic flux are predicted by many models of grand unification. It has been argued elsewhere that a generic transformation of the "unbroken" symmetry group H cannot be globally implemented on such monopoles for reasons of topology. In this paper, we show that similar topological obstructions are encountered in the mechanics of a test particle in the field of these monopoles and that the transformations of H cannot all be globally implemented as canonical transformations. For the SU(5) model, if H is SU(3)C×U(1)em, a consequence is that color multiplets are not globally defined, while if H is SU(3)C×SU(2)WS×U(1)Y, the same is the case for both color and electroweak multiplets. There are, however, several subgroups KT, KT′,… of H which can be globally implemented, with the transformation laws of the observables differing from group to group in a novel way. For H=SU(3)C×U(1)em, a choice for KT is SU(2)C×U(1)em, while for H=SU(3)C×SU(2)WS×U(1)Y, a choice is SU(2)C×U(1)×U(1)×U(1). The paper also develops the differential geometry of monopoles in a form convenient for computations.

Catalytic cyclopropanation of olefins using copper(I) diphosphinoamines

Catalytic cyclopropanation reactions of olefins with ethyl diazoacetate were carried out using copper(I) diphosphinoamine (PPh2)(2)N(R) (R = Pr-i, H, Ph and -CH2-C6H4-CH=CH2) complexes at 40 degrees C in chloroform. High yields of the cyclopropanes were obtained in all cases. The rate of the reaction was influenced by the nuclearity of the complex and the binding mode of the ligand which was either bridging or chelating. Comparison of isostructural complexes shows that the rate follows the order R = Pr-i > H > Ph, where R is the substituent on the N. However, cyclopropane formation versus dimerization of the carbene, and trans to cis ratios of cyclopropane was similar in all cases. The nearly identical selectivity for different products formed was indicative of a common catalytic intermediate. A labile "copper-olefin" complex which does not involve the phosphine or the counterion is the most likely candidate. The differences in the reaction rates for different complexes are attributed to differences in the concentration of the catalytically active species which are in equilibrium with the catalytically inactive copper-phosphinoamine complex. To test the hypothesis a diphosphinoamine polymer complexed to copper(I) was used as a heterogeneous catalyst. Leaching of copper(I) and deactivation of the catalyst confirmed the proposed mechanism. (C) 2008 Elsevier B. V. All rights reserved.

Effect of directionality of unidirectional grinding marks on friction and transfer layer formation of Mg on steel using inclined scratch test

Surface topography has been known to play an important role in the friction and transfer layer formation during sliding. In the present investigation, EN8 steel flats were ground to attain different surface roughness with unidirectional grinding marks. Pure Mg pins were scratched on these surfaces using an Inclined Scratch Tester to study the influence of directionality of surface grinding marks on coefficient of friction and transfer layer formation. Grinding angle (i.e., the angle between direction of scratch and grinding marks) was varied between 0 degrees and 90 degrees during the tests. Experiments were conducted under both dry and lubricated conditions. Scanning electron micrographs of the contact surfaces of pins and flats were used to reveal the surface features that included the morphology of the transfer layer. It was observed that the average coefficient of friction and transfer layer formation depend primarily on the directionality of the grinding marks but were independent of surface roughness on the harder mating surface. In addition, a stick-slip phenomenon was observed, the amplitude of which depended both on the directionality of grinding marks and the surface roughness of the harder mating surface. The grinding angle effect on the coefficient of friction, which consists of adhesion and plowing components, was attributed to the variation of plowing component of friction. (c) 2006 Elsevier B.V. All rights reserved.

Impedance parameters and the state-of charge. I. Nickel-cadmium battery

The problem of nondestructive determination of the state-of-charge of nickel-cadmium batteries has been examined experimentally as well as theoretically from the viewpoint of internal impedance. It is shown that the modulus of the impedance is mainly controlled by diffusion at all states of charge. Even so, a prediction of the state of charge is possible if the equivalent series/parallel capacitance or the alternating current phase shift is measured at a sufficiently low a.c. test frequency (5–30 Hz) which also avoids inductive effects. These results are explained on the basis of a uniform transmission-line analog equivalent circuit for the battery electrodes.

Perturbative growth of cosmological clustering. I: Formalism

Here we rederive the hierarchy of equations for the evolution of distribution functions of various orders using a convenient parameterization. We use this to obtain equations for two- and three-point correlation functions in powers of a small parameter, viz., the initial density contrast. The correspondence of the lowest order solutions of these equations to the results from the linear theory of density perturbations is shown for an OMEGA = 1 universe. These equations are then used to calculate, to the lowest order, the induced three-point correlation function that arises from Gaussian initial conditions in an OMEGA = 1 universe. We obtain an expression which explicitly exhibits the spatial structure of the induced three-point correlation function. It is seen that the spatial structure of this quantity is independent of the value of OMEGA. We also calculate the triplet momentum. We find that the induced three-point correlation function does not have the ''hierarchical'' form often assumed. We discuss possibilities of using the induced three-point correlation to interpret observational data. The formalism developed here can also be used to test a validity of different schemes to close the

V-Transform: “An Enhanced Polynomial Coefficient Based DC Test for Non-linear Analog Circuits

Abstract—DC testing of parametric faults in non-linear analog circuits based on a new transformation, entitled, V-Transform acting on polynomial coefficient expansion of the circuit function is presented. V-Transform serves the dual purpose of monotonizing polynomial coefficients of circuit function expansion and increasing the sensitivity of these coefficients to circuit parameters. The sensitivity of V-Transform Coefficients (VTC) to circuit parameters is up to 3x-5x more than sensitivity of polynomial coefficients. As a case study, we consider a benchmark elliptic filter to validate our method. The technique is shown to uncover hitherto untestable parametric faults whose sizes are smaller than 10 % of the nominal values. I.

Conditional silencing of topoisomerase I gene of Mycobacterium tuberculosis validates its essentiality for cell survival

Topoisomerases are an important class of enzymes for regulating the DNA transaction processes. Mycobacterium tuberculosis (Mtb) is one of the most formidable pathogens also posing serious challenges for therapeutic interventions. The organism contains only one type IA topoisomerase (Rv3646c), offering an opportunity to test its potential as a candidate drug target. To validate the essentiality of M.tuberculosis topoisomerase I (TopoI(Mt)) for bacterial growth and survival, we have generated a conditionally regulated strain of topoI in Mtb. The conditional knockdown mutant exhibited delayed growth on agar plate. In liquid culture, the growth was drastically impaired when TopoI expression was suppressed. Additionally, novobiocin and isoniazid showed enhanced inhibitory potential against the conditional mutant. Analysis of the nucleoid revealed its altered architecture upon TopoI depletion. These studies establish the essentiality of TopoI for the M.tuberculosis growth and open up new avenues for targeting the enzyme.

NUMERICAL STUDIES OF DYNAMO ACTION IN A TURBULENT SHEAR FLOW. I.

We perform numerical experiments to study the shear dynamo problem where we look for the growth of a large-scale magnetic field due to non-helical stirring at small scales in a background linear shear flow in previously unexplored parameter regimes. We demonstrate the large-scale dynamo action in the limit where the fluid Reynolds number (Re) is below unity while the magnetic Reynolds number (Rm) is above unity; the exponential growth rate scales linearly with shear, which is consistent with earlier numerical works. The limit of low Re is particularly interesting, as seeing the dynamo action in this limit would provide enough motivation for further theoretical investigations, which may focus attention on this analytically more tractable limit of Re < 1 compared to the more formidable limit of Re > 1. We also perform simulations in the regimes where (i) both (Re, Rm) < 1, and (ii) Re > 1 and Rm < 1, and compute all of the components of the turbulent transport coefficients (alpha(ij) and alpha(ij)) using the test-field method. A reasonably good agreement is observed between our results and the results of earlier analytical works in similar parameter regimes.

ANRC Hybrid Test Bed Implementation and an End-to-End Performance Characterization of Dynamic Spectrum Access

An abundance of spectrum access and sensing algorithms are available in the dynamic spectrum access (DSA) and cognitive radio (CR) literature. Often, however, the functionality and performance of such algorithms are validated against theoretical calculations using only simulations. Both the theoretical calculations and simulations come with their attendant sets of assumptions. For instance, designers of dynamic spectrum access algorithms often take spectrum sensing and rendezvous mechanisms between transmitter-receiver pairs for granted. Test bed designers, on the other hand, either customize so much of their design that it becomes difficult to replicate using commercial off the shelf (COTS) components or restrict themselves to simulation, emulation /hardware-in-Ioop (HIL), or pure hardware but not all three. Implementation studies on test beds sophisticated enough to combine the three aforementioned aspects, but at the same time can also be put together using COTS hardware and software packages are rare. In this paper we describe i) the implementation of a hybrid test bed using a previously proposed hardware agnostic system architecture ii) the implementation of DSA on this test bed, and iii) the realistic hardware and software-constrained performance of DSA. Snapshot energy detector (ED) and Cumulative Summation (CUSUM), a sequential change detection algorithm, are available for spectrum sensing and a two-way handshake mechanism in a dedicated control channel facilitates transmitter-receiver rendezvous.

Characterization of type I interferon pathway during hepatic differentiation of human pluripotent stem cells and hepatitis C virus infection

Pluripotent stem cells are being actively studied as a cell source for regenerating damaged liver. For long-term survival of engrafting cells in the body, not only do the cells have to execute liver-specific function but also withstand the physical strains and invading pathogens. The cellular innate immune system orchestrated by the interferon (IFN) pathway provides the first line of defense against pathogens. The objective of this study is to assess the innate immune function as well as to systematically profile the IFN-induced genes during hepatic differentiation of pluripotent stem cells. To address this objective, we derived endodermal cells (day 5 post-differentiation), hepatoblast (day 15) and hepatocyte-like cells (day 21) from human embryonic stem cells (hESCs). Day 5, 15 and 21 cells were stimulated with IFN-alpha and subjected to IFN pathway analysis. Transcriptome analysis was carried out by RNA sequencing. The results showed that the IFN-alpha treatment activated STAT-JAK pathway in differentiating cells. Transcriptome analysis indicated stage specific expression of classical and non-classical IFN-stimulated genes (ISGs). Subsequent validation confirmed the expression of novel ISGs including RASGRP3, CLMP and TRANK1 by differentiated hepatic cells upon IFN treatment. Hepatitis C virus replication in hESC-derived hepatic cells induced the expression of ISGs - LAMP3, ETV7, RASGRP3, and TRANK1. The hESC-derived hepatic cells contain intact innate system and can recognize invading pathogens. Besides assessing the tissue-specific functions for cell therapy applications, it may also be important to test the innate immune function of engrafting cells to ensure adequate defense against infections and improve graft survival. (C) 2015 The Authors. Published by Elsevier B.V.