targetTB: A target identification pipeline for Mycobacterium tuberculosis through an interactome, reactome and genome-scale structural analysis

Background: Tuberculosis still remains one of the largest killer infectious diseases, warranting the identification of newer targets and drugs. Identification and validation of appropriate targets for designing drugs are critical steps in drug discovery, which are at present major bottle-necks. A majority of drugs in current clinical use for many diseases have been designed without the knowledge of the targets, perhaps because standard methodologies to identify such targets in a high-throughput fashion do not really exist. With different kinds of 'omics' data that are now available, computational approaches can be powerful means of obtaining short-lists of possible targets for further experimental validation. Results: We report a comprehensive in silico target identification pipeline, targetTB, for Mycobacterium tuberculosis. The pipeline incorporates a network analysis of the protein-protein interactome, a flux balance analysis of the reactome, experimentally derived phenotype essentiality data, sequence analyses and a structural assessment of targetability, using novel algorithms recently developed by us. Using flux balance analysis and network analysis, proteins critical for survival of M. tuberculosis are first identified, followed by comparative genomics with the host, finally incorporating a novel structural analysis of the binding sites to assess the feasibility of a protein as a target. Further analyses include correlation with expression data and non-similarity to gut flora proteins as well as 'anti-targets' in the host, leading to the identification of 451 high-confidence targets. Through phylogenetic profiling against 228 pathogen genomes, shortlisted targets have been further explored to identify broad-spectrum antibiotic targets, while also identifying those specific to tuberculosis. Targets that address mycobacterial persistence and drug resistance mechanisms are also analysed. Conclusion: The pipeline developed provides rational schema for drug target identification that are likely to have high rates of success, which is expected to save enormous amounts of money, resources and time in the drug discovery process. A thorough comparison with previously suggested targets in the literature demonstrates the usefulness of the integrated approach used in our study, highlighting the importance of systems-level analyses in particular. The method has the potential to be used as a general strategy for target identification and validation and hence significantly impact most drug discovery programmes.

A Combination of Hexagonal and 12-Sided Polygonal Voltage Space Vector PWM Control for IM Drives Using Cascaded Two-Level Inverters

This paper proposes a multilevel inverter configuration which produces a hexagonal voltage space vector structure in the lower modulation region and a 12-sided polygonal space vector structure in the overmodulation region. A conventional multilevel inverter produces 6n plusmn 1 (n = odd) harmonics in the phase voltage during overmodulation and in the extreme square-wave mode of operation. However, this inverter produces a 12-sided polygonal space vector location, leading to the elimination of 6n plusmn 1 (n = odd) harmonics in the overmodulation region extending to a final 12-step mode of operation with a smooth transition. The benefits of this arrangement are lower losses and reduced torque pulsation in an induction motor drive fed from this converter at higher modulation indexes. The inverter is fabricated by using three conventional cascaded two-level inverters with asymmetric dc-bus voltages. A comparative simulation study of the harmonic distortion in the phase voltage and associated losses in conventional multilevel inverters and that of the proposed inverter is presented in this paper. Experimental validation on a prototype shows that the proposed converter is suitable for high-power applications because of low harmonic distortion and low losses.

Solid-state Thermal Polymerization of Sodium Acrylate

Initiation and propagation processes in thermally initiated solid-state polymerization of sodiumvacrylate have been studied. The kinetics of initiation, followed with the electron spin resonancev technique, leads to an activation energy E of 28.8 kcal/mol, which is attributed to the formation of dimeric radicals. The activation energy of 16 f 1 kcaVmol obtained for the solid-state polymerization of sodium acrylate by chemical analysis and differential scanning calorimetry has been attributed to the propagation process.

A fuzzy logic based dynamic wave model inversion algorithm for canal regulation

A fuzzy logic based centralized control algorithm for irrigation canals is presented. Purpose of the algorithm is to control downstream discharge and water level of pools in the canal, by adjusting discharge release from the upstream end and gates settings. The algorithm is based on the dynamic wave model (Saint-Venant equations) inversion in space, wherein the momentum equation is replaced by a fuzzy rule based model, while retaining the continuity equation in its complete form. The fuzzy rule based model is developed on fuzzification of a new mathematical model for wave velocity, the derivational details of which are given. The advantages of the fuzzy control algorithm, over other conventional control algorithms, are described. It is transparent and intuitive, and no linearizations of the governing equations are involved. Timing of the algorithm and method of computation are explained. It is shown that the tuning is easy and the computations are straightforward. The algorithm provides stable, realistic and robust outputs. The disadvantage of the algorithm is reduced precision in its outputs due to the approximation inherent in the fuzzy logic. Feed back control logic is adopted to eliminate error caused by the system disturbances as well as error caused by the reduced precision in the outputs. The algorithm is tested by applying it to water level control problem in a fictitious canal with a single pool and also in a real canal with a series of pools. It is found that results obtained from the algorithm are comparable to those obtained from conventional control algorithms.

Intrinsic Electron localization in manganites

We mention here an unusual disorder effect in manganites, namely the ubiquitous hopping behavior for electron transport observed in them over a wide range of doping. We argue that the implied Anderson localization is intrinsic to manganites, because of the existence of polarons in them which are spatially localized, generally at random sites (unless there is polaron ordering). We have developed a microscopic two fluid lb model for manganites, where l denotes lattice site localized l polarons, and b denotes band electrons. Using this, and the self-consistent theory of localization, we show that the occupied b states are Anderson localized in a large range of doping due to the scattering of b electrons from l polarons. Numerical simulations which further include the effect of long range Coulomb interactions support this, as well the existence of a novel polaronic Coulomb glass. A consequence is the inevitable hopping behaviour for electron transport observed in doped insulating manganites.

Refinement of the thermodynamic properties of ruthenium dioxide and osmium dioxide

The standard Gibbs energies of formation of RuO2 and OsO2 at high temperature have been determined with high precision, using a novel apparatus that incorporates a buffer electrode between the reference and working electrodes, The buffer electrode absorbs the electrochemical flux of oxygen through the solid electrolyte from the electrode with higher oxygen chemical potential to the electrode with lower oxygen potential, The buffer electrode prevents polarization of the measuring electrode and ensures accurate data, The standard Gibbs energies of formation (Delta(f)G degrees) of RuO2, in the temperature range of 900-1500 K, and OsO2, in the range of 900-1200 K, can be represented by the equations Delta(f)G degrees(RuO2)(J/mol) = -324 720 + 354.21T - 23.490T In T Delta(f)G degrees(OsO2)(J/mol) = -304 740 + 318.80T - 18.444T In T where the temperature T is given in Kelvin and the deviation of the measurement is +/- 80 J/mol, The high-temperature heat ;capacities of RuO2 and OsO2 are measured using differential scanning calorimetry. The information for both the low- and high-temperature heat rapacity of RuO2 is coupled with the Delta(f)G degrees data obtained in this study to evaluate the standard enthalpy of formation of RuO2 at 298.15 K (Delta(f)H degrees(298.15K)). The low-temperature heat capacity of OsO2 has not been measured: therefore, the standard enthalpy and entropy of formation of OsO2 at 298.15 K (Delta(f)H degrees(298.15K) and S degrees(298.15K), respectively) are derived simultaneously through an optimization procedure from the high-temperature heat capacity and the Gibbs energy of formation. Both Delta fH degrees(298.15K) and S degrees(298.15K) are treated as variables in the optimization routine, For RuO2, the standard enthalpy of formation at 298.15 K is Delta fH degrees(298.15K) (RuO2) -313.52 +/- 0.08 kJ/mol, and that for OsO2 is Delta(f)H degrees(298.15K) (OSO2) = -295.96 +/- 0.08 kJ/mol. The standard entropy of OsO2 at 298.15 K that has been obtained from the optimization is given as S degrees(298.15K) (OsO2) = 49.8 +/- 0.2 J (mol K)(-1).

Nonlinear I-V characteristics of nanocrystalline SnO2

Current versus voltage characteristics (I-V) of nanocrystalline SnO2 materials have been investigated in air at room temperature. The samples were prepared by the inert gas condensation technique (IGCT) as well as by chemical methods. X-ray diffraction studies showed a tetragonal rutile structure for all the samples. Microstructural studies were performed with transmission electron microscopy. All the samples exhibited nonlinear I-V characteristics of the current-controlled negative resistance (CCNR) type. The results show that the threshold field (break down) voltage is higher for the samples prepared by the IGCT method than for those prepared by the chemical method due to the formation of a tin oxide layer over the crystalline tin. It is also found that the threshold field increases with the decrease in grain size.

Optimal Weighted Antenna Selection For Imperfect Channel Knowledge From Training

Receive antenna selection (AS) reduces the hardware complexity of multi-antenna receivers by dynamically connecting an instantaneously best antenna element to the available radio frequency (RF) chain. Due to the hardware constraints, the channels at various antenna elements have to be sounded sequentially to obtain estimates that are required for selecting the ``best'' antenna and for coherently demodulating data. Consequently, the channel state information at different antennas is outdated by different amounts. We show that, for this reason, simply selecting the antenna with the highest estimated channel gain is not optimum. Rather, the channel estimates of different antennas should be weighted differently, depending on the training scheme. We derive closed-form expressions for the symbol error probability (SEP) of AS for MPSK and MQAM in time-varying Rayleigh fading channels for arbitrary selection weights, and validate them with simulations. We then derive an explicit formula for the optimal selection weights that minimize the SEP. We find that when selection weights are not used, the SEP need not improve as the number of antenna elements increases, which is in contrast to the ideal channel estimation case. However, the optimal selection weights remedy this situation and significantly improve performance.

Structure of ant assemblages in Western Ghats, India: role of habitat, disturbance and introduced species

1. Habitat fragmentation, anthropogenic disturbance and the introduction of invasive species are factors thought to structure ant assemblages. To understand responses of the ant community to changes in the environment, ants are commonly categorised into functional groups, a scheme developed and based on Australian ants. 2. Behaviourally dominant and aggressive ants of the dominant dolichoderinae functional group have been suggested to structure the ant assemblages in arid and semi-arid habitats of these regions. Given the limited geographical distribution of dominant dolichoderinae, it is crucial to determine the responses of the ant community to changes in the environment in their absence. 3. This study addresses this less studied aspect by considering the associations of ants of Western Ghats, India, with habitat, anthropogenic disturbance and introduced ants. We determined how ant functional groups respond to these factors in this region, where dominant dolichoderines are naturally absent, and whether responses are consistent with predictions derived from the ant functional group scheme. 4. This study provides new information on ant assemblages in a little-studied region. As in other parts of the world, ant assemblages in Western Ghats were strongly influenced by habitat and disturbance, with different functional groups associated with different habitats and levels of disturbance. 5. No functional group showed evidence of being influenced by the abundance of introduced species. In addition, predictions of negative interactions between functional groups were not supported. Our findings suggest that abiotic factors are universal determinants of ant assemblage structure, but that competitive interactions may not be.

Microhabitat selection in an assemblage of crickets (Orthoptera: Ensifera) of a tropical evergreen forest in Southern India

1. Habitat selection is a universal aspect of animal ecology that has important fitness consequences and may drive patterns of spatial organisation in ecological communities. 2. Measurements of habitat selection have mostly been carried out on single species and at the landscape level. Quantitative studies examining microhabitat selection at the community level are scarce, especially in insects. 3. In this study, microhabitat selection in a natural assemblage of cricket species was examined for the first time using resource selection functions (RSF), an approach more commonly applied in studies of macrohabitat selection. 4. The availability and differential use of six microhabitats by 13 species of crickets inhabiting a tropical evergreen forest in southern India was examined. The six available microhabitats included leaf litter-covered ground, tree trunks, dead logs, brambles, understorey and canopy foliage. The area offered by the six microhabitats was estimated using standard methods of forest structure measurement. Of the six microhabitats, the understorey and canopy accounted for approximately 70% of the total available area. 5. The use of different microhabitats by the 13 species was investigated using acoustic sampling of crickets to locate calling individuals. Using RSF, it was found that of 13 cricket species examined, 10 showed 100% selection for a specific microhabitat. Of these, two species showed fairly high selection for brambles and dead logs, which were rare microhabitats, highlighting the importance of preserving all components of forest structure.

A total synthesis of 11-O-methyldebenzoyltashironin

A concise total synthesis of 11-O-methyldebenzoyltashironin is reported in which oxidative dearomatization-IMDA-RCM triad constitutes the key ring forming steps, while an unorthodox DIBAL-H mediated stereo- and regioselective reductive epoxide openings and implementation of the vinyl bromide-carbonyl equivalency concept were pivotal to the success of this endeavor. (C) 2011 Elsevier Ltd. All rights reserved.

A note on magnetization of high temperature superconductors (YBCO, BSCCO) in mixed state

We present a critical study of the temperature and field dependence magnetization of high temperature superconductors (HTSCs). The controversial field dependence of dM/dInB for YBa(2)Cu(3)O(7) (YBCO) and Bi(2)Sr(2)CaCu(2)O(8) (BSCCO) is discussed using different models. Moreover, for both the systems the magnetization (M(H)) dependence is compared with field (H) dependence. (C) 2011 Elsevier B.V. All rights reserved.

Physically Based, Hydrologic Model Results Based on Three Precipitation Products

The main objective of the study is to examine the accuracy of and differences among simulated streamflows driven by rainfall estimates from a network of 22 rain gauges spread over a 2,170 km2 watershed, NEXRAD Stage III radar data, and Tropical Rainfall Measuring Mission (TRMM) 3B42 satellite data. The Gridded Surface Subsurface Hydrologic Analysis (GSSHA), a physically based, distributed parameter, grid-structured, hydrologic model, was used to simulate the June-2002 flooding event in the Upper Guadalupe River watershed in south central Texas. There were significant differences between the rainfall fields estimated by the three types of measurement technologies. These differences resulted in even larger differences in the simulated hydrologic response of the watershed. In general, simulations driven by radar rainfall yielded better results than those driven by satellite or rain-gauge estimates. This study also presents an overview of effects of land cover changes on runoff and stream discharge. The results demonstrate that, for major rainfall events similar to the 2002 event, the effect of urbanization on the watershed in the past two decades would not have made any significant effect on the hydrologic response. The effect of urbanization on the hydrologic response increases as the size of the rainfall event decreases.

Effect of lipopolysaccharide on alteration of phospholipids and their fatty acid composition in spleen and thymus by in vitro metabolic labeling

Lipopolysaccharide (LPS) is an endotoxin, a potent stimulator of immune response and induction of LPS leads to acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). ARDS is a life-threatening disease worldwide with a high mortality rate. The immunological effect of LPS with spleen and thymus is well documented; however the impact on membrane phospholipid during endotoxemia has not yet been studied. Hence we aimed to investigate the influence of LPS on spleen and thymus phospholipid and fatty acid composition by 32P]orthophosphate labeling in rats. The in vitro labeling was carried out with phosphate-free medium (saline). Time course, LPS concentration-dependent, pre- and post-labeling with LPS and fatty acid analysis of phospholipid were performed. Labeling studies showed that 50 mu g LPS specifically altered the major phospholipids, phosphatidylcholine and phosphatidylglycerol in spleen and phosphatidylcholine in thymus. Fatty acid analysis showed a marked alteration of unsaturated fatty acids/saturated fatty acids in spleen and thymus leading to immune impairment via the fatty acid remodeling pathway. Our present in vitro lipid metabolic labeling study could open up new vistas for exploring LPS-induced immune impairment in spleen and thymus, as well as the underlying mechanism.