Crowd Sourcing a New Paradigm for Interactome Driven Drug Target Identification in Mycobacterium tuberculosis

A decade since the availability of Mycobacterium tuberculosis (Mtb) genome sequence, no promising drug has seen the light of the day. This not only indicates the challenges in discovering new drugs but also suggests a gap in our current understanding of Mtb biology. We attempt to bridge this gap by carrying out extensive re-annotation and constructing a systems level protein interaction map of Mtb with an objective of finding novel drug target candidates. Towards this, we synergized crowd sourcing and social networking methods through an initiative `Connect to Decode' (C2D) to generate the first and largest manually curated interactome of Mtb termed `3interactome pathway' (IPW), encompassing a total of 1434 proteins connected through 2575 functional relationships. Interactions leading to gene regulation, signal transduction, metabolism, structural complex formation have been catalogued. In the process, we have functionally annotated 87% of the Mtb genome in context of gene products. We further combine IPW with STRING based network to report central proteins, which may be assessed as potential drug targets for development of drugs with least possible side effects. The fact that five of the 17 predicted drug targets are already experimentally validated either genetically or biochemically lends credence to our unique approach.

Radio interference measurements on a ceramic disc insulator string with field reduction electrode

This paper presents a laboratory study of the discharge radio noise generated by ceramic insulator strings under normal conditions. In the course of study, a comparison on the performance of two types of insulator strings under two different conditions was studied namely (a) normal disc insulators in a string and (b) disc insulators integrated with a newly developed field reduction electrode fixed to the disc insulator at the pin junction. The results obtained during the study are discussed and presented.

Potential and electric field distribution in a ceramic disc insulator string with faulty insulators

Ceramic/Porcelain suspension disc insulators are widely used in power systems to provide electrical insulation and mechanically support for high-voltage transmission lines. These insulators are subjected to a variety of stresses, including mechanical, electrical and environmental. These stresses act in unison. The exact nature and magnitude of these stresses vary significantly and depends on insulator design, application and its location. Due to various reasons the insulator disc can lose its electrical insulation properties without any noticeable mechanical failure. Such a condition while difficult to recognize, can enhance the stress on remaining healthy insulator discs in the string further may lead to a flashover. To understand the stress enhancement due to faulty discs in a string, attempt has been made to simulate the potential and electric field profiles for various disc insulators presently used in the country. The results of potential and electric filed stress obtained for normal and strings with faulty insulator discs are presented.

Hybrid stiff-string-polynomial basis functions for vibration analysis of high speed rotating beams

A new finite element is developed for free vibration analysis of high speed rotating beams using basis functions which use a linear combination of the solution of the governing static differential equation of a stiff-string and a cubic polynomial. These new shape functions depend on rotation speed and element position along the beam and account for the centrifugal stiffening effect. The natural frequencies predicted by the proposed element are compared with an element with stiff-string, cubic polynomial and quintic polynomial shape functions. It is found that the new element exhibits superior convergence compared to the other basis functions.

Negative resistance mode of forced oscillations of a string

A new mode of driven nonlinear vibrations of a stretched string is investigated with reference to conditions of existence, properties, and regions of stability. It is shown that this mode exhibits negative resistance properties at all frequencies and driving force amplitudes. Discovery of this mode helps to fill certain gaps in the theory of forced nonlinear vibrations of strings.

Performance studies on mechanical + adsorption hybrid compression refrigeration cycles with HFC 134a

This paper presents the results of an investigation on the efficacy of hybrid compression process for refrigerant HFC 134a in cooling applications. The conventional mechanical compression is supplemented by thermal compression using a string of adsorption compressors. Activated carbon is the adsorbent for the thermal compression segment. The alternatives of bottoming either mechanical or thermal compression stages are investigated. It is shown that almost 40% energy saving is realizable by carrying out a part of the compression in a thermal compressor compared to the case when the entire compression is carried out in a single-stage mechanical compressor. The hybrid compression is feasible even when low grade heat is available. Some performance indictors are defined and evaluated for various configurations.

Stiff-String Basis Functions for Vibration Analysis of High Speed Rotating Beams

A new rotating beam finite element is developed in which the basis functions are obtained by the exact solution of the governing static homogenous differential equation of a stiff string, which results from an approximation in the rotating beam equation. These shape functions depend on rotation speed and element position along the beam and account for the centrifugal stiffening effect. Using this new element and the Hermite cubic finite element, a convergence study of natural frequencies is performed, and it is found that the new element converges much more rapidly than the conventional Hermite cubic element for the first two modes at higher rotation speeds. The new element is also applied for uniform and tapered rotating beams to determine the natural frequencies, and the results compare very well with the published results given in the literature.

Probability Distribution of the Eigenvalues of the Random String Equation

The probability distribution of the eigenvalues of a second-order stochastic boundary value problem is considered. The solution is characterized in terms of the zeros of an associated initial value problem. It is further shown that the probability distribution is related to the solution of a first-order nonlinear stochastic differential equation. Solutions of this equation based on the theory of Markov processes and also on the closure approximation are presented. A string with stochastic mass distribution is considered as an example for numerical work. The theoretical probability distribution functions are compared with digital simulation results. The comparison is found to be reasonably good.

Investigations on the Corona performance of a Ceramic disc Insulators integrated with Field Reduction Electrode

This paper presents laboratory investigations on the visible corona and discharge radio noise. Experimental investigations are carried on various types of normal and anti-fog types of ceramic disc insulator at the recently established artificial pollution experimental facility. The results obtained from the experimental investigations show better performance for the disc insulators fitted with field reduction electrodes. In addition to the corona and radio noise investigations the comparisons are also made for the experimental results of the potential distribution across the insulator string (with and without filed reduction electrode) with the simulation results obtained by using Surface Charge Simulation Method.

Linear dynamics and active control of an elastically supported travelling string

In this paper, the linear dynamics and active control of a string travelling with uniform velocity is presented. Discrete elastic supports are introduced along the length of the string. Finite element formulation is adopted to obtain the governing equations of motion. The velocity of translation introduces gyroscopic terms in the system equations. The effect of translation and the discrete elastic supports on the free vibration solution is studied. The solution is utilized in actively controlling the string vibrations due to an initial disturbance. The control, affected in modal space, is optimal with respect to a quadratic performance index. Numerical results are presented to demonstrate the effectiveness of the control strategy in regulating the travelling string vibrations.

Study of temperature distribution along an artificially polluted insulator string

Insulator becomes wet partially or completely, and the pollution layer on it becomes conductive, when collecting pollutants for an extended period during dew, light rain, mist, fog or snow melting. Heavy rain is a complicated factor that it may wash away the pollution layer without initiating other stages of breakdown or it may bridge the gaps between sheds to promote flashover. The insulator with a conducting pollution layer being energized, can cause a surface leakage current to flow (also temperature-rise). As the surface conductivity is non-uniform, the conducting pollution layer becomes broken by dry bands (at spots of high current density), interrupting the flow of leakage current. Voltage across insulator gets concentrated across dry bands, and causes high electric stress and breakdown (dry band arcing). If the resistance of the insulator surface is sufficiently low, the dry band arcs can be propagated to bridge the terminals causing flashover. The present paper concerns the evaluation of the temperature distribution along the surface of an energized artificially polluted insulator string.

String-like propagation of the 5-coordinated defect state in supercooled water: molecular origin of dynamic and thermodynamic anomalies

We find that at low temperature water, large amplitude (similar to 60 degrees) rotational jumps propagate like a string, with the length of propagation increasing with lowering temperature. The strings are formed by mobile 5-coordinated water molecules which move like a Glarum defect (J. Chem. Phys., 1960, 33, 1371), causing water molecules on the path to change from 4-coordinated to 5-coordinated and again back to 4-coordinated water, and in the process cause the tagged water molecule to jump, by following essentially the Laage-Hynes mechanism (Science, 2006, 311, 832-835). The effects on relaxation of the propagating defect causing large amplitude jumps are manifested most dramatically in the mean square displacement (MSD) and also in the rotational time correlation function of the O-H bond of the molecule that is visited by the defect (transient transition to the 5-coordinated state). The MSD and the decay of rotational time correlation function, both remain quenched in the absence of any visit by the defect, as postulated by Glarum long time ago. We establish a direct connection between these propagating events and the known thermodynamic and dynamic anomalies in supercooled water. These strings are found largely in the regions that surround the relatively rigid domains of 4-coordinated water molecules. The propagating strings give rise to a noticeable dynamical heterogeneity, quantified here by a sharp rise in the peak of the four-point density response function, chi(4)(t). This dynamics heterogeneity is also responsible for the breakdown of the Stokes-Einstein relation.

Instabilities of soft elastic microtubes filled with viscous fluids: Pearls, wrinkles, and sausage strings

A linear stability analysis is presented to study the self-organized instabilities of a highly compliant elastic cylindrical shell filled with a viscous liquid and submerged in another viscous medium. The prototype closely mimics many components of micro-or nanofluidic devices and biological processes such as the budding of a string of pearls inside cells and sausage-string formation of blood vessels. The cylindrical shell is considered to be a soft linear elastic solid with small storage modulus. When the destabilizing capillary force derived from the cross-sectional curvature overcomes the stabilizing elastic and in-plane capillary forces, the microtube can spontaneously self-organize into one of several possible configurations; namely, pearling, in which the viscous fluid in the core of the elastic shell breaks up into droplets; sausage strings, in which the outer interface of the mircrotube deforms more than the inner interface; and wrinkles, in which both interfaces of the thin-walled mircrotube deform in phase with small amplitudes. This study identifies the conditions for the existence of these modes and demonstrates that the ratios of the interfacial tensions at the interfaces, the viscosities, and the thickness of the microtube play crucial roles in the mode selection and the relative amplitudes of deformations at the two interfaces. The analysis also shows asymptotically that an elastic fiber submerged in a viscous liquid is unstable for Y = gamma/(G(e)R) > 6 and an elastic microchannel filled with a viscous liquid should rupture to form spherical cavities (pearling) for Y > 2, where gamma, G(e), and R are the surface tension, elastic shear modulus, and radius, respectively, of the fiber or microchannel.

Correlation between corona current and radio interference due to high voltage insulator string

The Radio Interference (RI) from electric power transmission line hardware, if not controlled, poses serious electromagnetic interference to system in the vicinity. The present work mainly concerns with the RI from the insulator string along with the associated line hardware. The laboratory testing for the RI levels are carried out through the measurement of the conducted radio interference levels. However such measurements do not really locate the coronating point, as well as, the mode of corona. At the same time experience shows that it is rather difficult to locate the coronating points by mere inspection. After a thorough look into the intricacies of the problem, it is ascertained that the measurement of associated ground end currents could give a better picture of the prevailing corona modes and their intensities. A study on the same is attempted in the present work. Various intricacies of the problem,features of ground end current pulses and its correlation with RI are dealt with. Owing to the complexity of such experimental investigations, the study made is not fully complete nevertheless it seems to be first of its kind.

Simulation of potential and electric field across faulty ceramic disc insulator string

Ceramic/Porcelain insulators are widely used in power transmission lines to provide mechanical support for High voltage conductors in addition to withstand electrical stresses. As a result of lightning, switching or temporary over voltages that could initiate flashover under worst weather conditions, and to operate within interference limits. Given that the useful life in service of the individual insulator elements making up the insulator strings is hard to predict, they must be verified periodically to ensure that adequate line reliability is maintained at all times. Over the years utilities have adopted few methods to detect defective discs in a string, subsequently replacement of the faulty discs are being carried out for smooth operation. But, if the insulator is found to be defective in a string at some location that may not create any changes in the field configuration, there is no need to replace to avoid manpower and cost of replacement. Due to deficiency of electric field data for the existing string configuration, utilities are forced to replace the discs which may not be essentially required. Hence, effort is made in the present work to simulate the potential and electric field along the normal and with faults induced discs in a string up to 765 kV system voltages using Surface Charge Simulation Method (SCSM). A comparison is made between simulated results, experimental and field data and it was found that the computed results are quite acceptable and useful.