Mycobacterium tuberculosis mutT1 (Rv2985) and ADPRase (Rv1700) proteins constitute a two-stage mechanism of 8-Oxo-dGTP and 8-Oxo-GTP detoxification and adenosine to cytidine mutation avoidance

Approximately one third of the world population is infected with Mycobacterium tuberculosis, the causative agent of tuberculosis. A better understanding of the pathogen biology is crucial to develop new tools/strategies to tackle its spread and treatment. In the host macrophages, the pathogen is exposed to reactive oxygen species, known to damage dGTP and GTP to 8-oxo-dGTP and 8-oxo-GTP, respectively. Incorporation of the damaged nucleotides in nucleic acids is detrimental to organisms. MutT proteins, belonging to a class of Nudix hydrolases, hydrolyze 8-oxo-G nucleoside triphosphates/diphosphates to the corresponding nucleoside monophosphates and sanitize the nucleotide pool. Mycobacteria possess several MutT proteins. However, a functional homolog of Escherichia coli MutT has not been identified. Here, we characterized MtuMutT1 and Rv1700 proteins of M. tuberculosis. Unlike other MutT proteins, MtuMutT1 converts 8-oxo-dGTP to 8-oxo-dGDP, and 8-oxo-GTP to 8-oxo-GDP. Rv1700 then converts them to the corresponding nucleoside monophosphates. This observation suggests the presence of a two-stage mechanism of 8-oxo-dGTP/8-oxo-GTP detoxification in mycobacteria. MtuMutT1 converts 8-oxo-dGTP to 8-oxo-dGDP with a K-m of similar to 50 mu M and V-max of similar to 0.9 pmol/min per ng of protein, and Rv1700 converts 8-oxo-dGDP to 8-oxo-dGMP with a K-m of similar to 9.5 mu M and V-max of similar to 0.04 pmol/min per ng of protein. Together, MtuMutT1 and Rv1700 offer maximal rescue to E. coli for its MutT deficiency by decreasing A to C mutations (a hallmark of MutT deficiency). We suggest that the concerted action of MtuMutT1 and Rv1700 plays a crucial role in survival of bacteria against oxidative stress.

Can the viscosity in astrophysical black hole accretion disks be close to its string theory bound?

String theory and gauge/gravity duality suggest the lower bound of shear viscosity (eta) to entropy density (s) for any matter to be mu h/4 pi k(B), when h and k(B) are reduced Planck and Boltzmann constants respectively and mu <= 1. Motivated by this, we explore eta/s in black hole accretion flows, in order to understand if such exotic flows could be a natural site for the lowest eta/s. Accretion flow plays an important role in black hole physics in identifying the existence of the underlying black hole. This is a rotating shear flow with insignificant molecular viscosity, which could however have a significant turbulent viscosity, generating transport, heat and hence entropy in the flow. However, in presence of strong magnetic field, magnetic stresses can help in transporting matter independent of viscosity, via celebrated Blandford-Payne mechanism. In such cases, energy and then entropy produces via Ohmic dissipation. In,addition, certain optically thin, hot, accretion flows, of temperature greater than or similar to 10(9) K, may be favourable for nuclear burning which could generate/absorb huge energy, much higher than that in a star. We find that eta/s in accretion flows appears to be close to the lower bound suggested by theory, if they are embedded by strong magnetic field or producing nuclear energy, when the source of energy is not viscous effects. A lower bound on eta/s also leads to an upper bound on the Reynolds number of the flow.

Biotin-conjugated tumour-targeting photocytotoxic iron(III) complexes

Iron(III) complexes FeL(B)] (1-4) of a tetradentate phenolate-based ligand (H3L) and biotin-conjugated dipyridophenazine bases (B), viz. 7-aminodipyrido 3,2-a: 2',3'-c]-phenazine (dppza in 1), (N-dipyrido3,2-a: 2',3'-c]-phenazino) amidobiotin (dppzNB in 2), dipyrido 3,2-a: 2',3'-c]-phenazine-11-carboxylic acid (dppzc in 3) and 2-((2-biotinamido) ethyl) amidodipyrido 3,2-a: 2',3'-c]-phenazine (dppzCB in 4) are prepared, characterized and their interaction with streptavidin and DNA and their photocytotoxicity and cellular uptake in various cells studied. The high-spin iron(III) complexes display Fe(III)/Fe(II) redox couple near -0.7V versus saturated calomel electrode in dimethyl sulfoxide-0.1M tetrabutylammonium perchlorate. The complexes show non-specific interaction with DNA as determined from the binding studies. Complexes with appended biotin moiety show similar binding to streptavidin as that of free biotin, suggesting biotin conjugation to dppz does not cause any loss in its binding affinity to streptavidin. The photocytotoxicity of the complexes is tested in HepG2, HeLa and HEK293 cell lines. Complex 2 shows higher photocytotoxicity in HepG2 cells than in HeLa or HEK293, forming reactive oxygen species. This effect is attributed to the presence of overexpressed sodium-dependent multi-vitamin transporters in HepG2 cells. Microscopic studies in HepG2 cells show internalization of the biotin complexes 2 and 4 essentially occurring by receptor-mediated endocytosis, which is similar to that of native biotin and biotin fluorescein isothiocyanate conjugate.

Implications of Higgs boson to diphoton decay rate in the bilinear R-parity violating supersymmetric model

The Large Hadron Collider has recently discovered a Higgs-like particle having a mass around 125 GeVand also indicated that there is an enhancement in the Higgs to diphoton decay rate as compared to that in the standard model. We have studied implications of these discoveries in the bilinear R-parity violating supersymmetric model, whose main motivation is to explain the nonzero masses for neutrinos. The R-parity violating parameters in this model are epsilon and b(epsilon), and these parameters determine the scale of neutrino masses. If the enhancement in the Higgs to diphoton decay rate is true, then we have found epsilon greater than or similar to 0.01 GeV and b epsilon similar to 1 GeV2 in order to be compatible with the neutrino oscillation data. Also, in the above mentioned analysis, we can determine the soft masses of sleptons (m(L)) and CP-odd Higgs boson mass (mA). We have estimated that m(L) greater than or similar to 300 GeV and m(A) greater than or similar to 700 GeV. We have also commented on the allowed values of epsilon and b(epsilon), in case there is no enhancement in the Higgs to diphoton decay rate. Finally, we present a model to explain the smallness of epsilon and b(epsilon).

Sea-level changes and its impact on coastal archaeological monuments: seven pagodas of Mahabalipuram, a case study

The name `Seven Pagodas' has served as a nickname for the south Indian port of Mahabalipuram since the early European explorers used it as landmark for navigation as they could see summits of seven temples from the sea. There are many theories concerning the name Seven Pagodas. The present study has compared coastline and adjacent seven monuments illustrated in a 17th century Portolan Chart (maritime map) with recent remote sensing data. This analysis throws new light on the name ``Seven Pagodas'' for the city. This study has used DEM of the site to simulate the coastline which is similar to the one depicted in the old portolan chart. Through this, the then sea level and corresponding flooding extent according to topography of the area and their effect on monuments could be analyzed. Most importantly this work has in the process identified possibly the seven monuments that constituted the name Seven Pagodas and this provides an alternative explanation to one of the mysteries of history. This work has demonstrated unique method of studying coastal archaeological sites. As large numbers of heritage sites around the world are on coastlines, this methodology has potential to be very useful for coastal heritage preservation and management.

Selenium adsorption on Au(111) and Ag(111) surfaces: adsorbed selenium and selenide films

Results of a high resolution photoemission and electrochemistry study of Se adsorption Au(111) and Ag(111) surfaces performed by immersion of pristine samples into an aqeuous solution of Na2Se are presented. Cyclic voltammetry on Au shows formation of selenium adsorbed species and the structures observed in reductive desorption are to the atomic and polymeric species observed in XPS. In the case of Au(111) XPS spectra in the Se(3d) region indeed show two main features attributed to Se chemisorbed atomically and polymeric Se-8 features.' Smaller structures due to other types of Se conformations were also observed. The Au(4f) peak line, shape does not show core level, shifts: indicative of Au selenide formation the case of silver, XPS spectra for the Ag(3d) show a broadening of the peak and a deconvolution into Ag-B bulk like Ag-Se components shows that the Ag-Se is located at a lower binding energy, an effect similar to oxidation and sulfidation of Ag. The Se(3d) XPS spectrum is found to be substantially different from the Au case and dominated by atomic type Se due to the selenide, though a smaller intensity Se structure at an energy similar to the Se-8 structure for Au is also observed. Changes in the valence band region. related to Se adsorption are reported.

Warped alternatives to Froggatt-Nielsen models

We consider the Randall-Sundrum (RS) setup to be a theory of flavor, as an alternative to Froggatt-Nielsen models instead of as a solution to the hierarchy problem. The RS framework is modified by taking the low-energy brane to be at the grand unified theory (GUT) scale. This also alleviates constraints from flavor physics. Fermion masses and mixing angles are fit at the GUT scale. The ranges of the bulk mass parameters are determined using a chi(2) fit taking into consideration the variation in O(1) parameters. In the hadronic sector, the heavy top quark requires large bulk mass parameters localizing the right-handed top quark close to the IR brane. Two cases of neutrino masses are considered: (a) Planck scale lepton number violation and (b) Dirac neutrino masses. Contrary to the case of weak scale RS models, both these cases give reasonable fits to the data, with the Planck scale lepton number violation fitting slightly better compared to the Dirac case. In the supersymmetric version, the fits are not significantly different except for the variation in tan beta. If the Higgs superfields and the supersymmetry breaking spurion are localized on the same brane, then the structure of the sfermion masses are determined by the profiles of the zero modes of the hypermultiplets in the bulk. Trilinear terms have the same structure as the Yukawa matrices. The resultant squark spectrum is around similar to 2-3 TeV required by the light Higgs mass to be around 125 GeV and to satisfy the flavor violating constraints.

Spark plasma sintering may lead to phase instability and inferior mechanical properties: A case study with TiB2

In contrast to the widely reported beneficial aspects of spark plasma sintering in developing materials with better properties, we report here two interesting aspects recorded with difficult-to-sinter titanium diboride: (a) in situ formation of second phase (TiB) and (b) inferior hardness (by similar to 30%) and elastic modulus (by similar to 20%) for spark plasma sintered TiB2, with respect to hot pressed TiB2. The formation of TiB is discussed with reference to the enhanced reaction kinetics in the presence of pulsed electric field. (C) 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Characterization of groundwater chemistry under the influence of lithologic and anthropogenic factors along a climatic gradient in Upper Cauvery basin, South India

Hydrogeological and climatic effect on chemical behavior of groundwater along a climatic gradient is studied along a river basin. `Semi-arid' (500-800 mm of mean annual rainfall), `sub-humid' (800-1,200 mm/year) and `humid' (1,200-1,500 mm/year) are the climatic zones chosen along the granito-gneissic plains of Kabini basin in South India for the present analysis. Data on groundwater chemistry is initially checked for its quality using NICB ratio (<+/- 5 %), EC versus TZ+ (similar to 0.85 correlation), EC versus TDS and EC versus TH analysis. Groundwater in the three climatic zones is `hard' to `very hard' in terms of Ca-Mg hardness. Polluted wells are identified (> 40 % of pollution) and eliminated for the characterization. Piper's diagram with mean concentrations indicates the evolution of CaNaHCO3 (semi-arid) from CaHCO3 (humid zone) along the climatic gradient. Carbonates dominate other anions and strong acids exceeded weak acids in the region. Mule Hole SEW, an experimental watershed in sub-humid zone, is characterized initially using hydrogeochemistry and is observed to be a replica of entire sub-humid zone (with 25 wells). Extension of the studies for the entire basin (120 wells) showed a chemical gradient along the climatic gradient with sub-humid zone bridging semi-arid and humid zones. Ca/Na molar ratio varies by more than 100 times from semi-arid to humid zones. Semi-arid zone is more silicaceous than sub-humid while humid zone is more carbonaceous (Ca/Cl similar to 14). Along the climatic gradient, groundwater is undersaturated (humid), saturated (sub-humid) and slightly supersaturated (semi-arid) with calcite and dolomite. Concentration-depth profiles are in support of the geological stratification i.e., not approximate to 18 m of saprolite and similar to 25 m of fracture rock with parent gneiss beneath. All the wells are classified into four groups based on groundwater fluctuations and further into `deep' and `shallow' based on the depth to groundwater. Higher the fluctuations, larger is its impact on groundwater chemistry. Actual seasonal patterns are identified using `recharge-discharge' concept based on rainfall intensity instead of traditional monsoon-non-monsoon concept. Non-pumped wells have low Na/Cl and Ca/Cl ratios in recharge period than in discharge period (Dilution). Few other wells, which are subjected to pumping, still exhibit dilution chemistry though water level fluctuations are high due to annual recharge. Other wells which do not receive sufficient rainfall and are constantly pumped showed high concentrations in recharge period rather than in discharge period (Anti-dilution). In summary, recharge-discharge concept demarcates the pumped wells from natural deep wells thus, characterizing the basin.

CMOS-Compatible and Scalable Deposition of Nanocrystalline Zinc Ferrite Thin Film to Improve Inductance Density of Integrated RF Inductor

Development towards the combination of miniaturization and improved functionality of RFIC has been stalled due to the lack of high-performance integrated inductors. To meet this challenge, integration of magnetic material with high permeability as well as low conductivity is a must. Ferrite films are excellent candidates for RF devices due to their low cost, high resistivity, and low eddy current losses. Unlike its bulk counterpart, nanocrystalline zinc ferrite, because of partial inversion in the spinel structure, exhibits novel magnetic properties suitable for RF applications. However, most scalable ferrite film deposition processes require either high temperature or expensive equipment or both. We report a novel low temperature (< 200 degrees C) solution-based deposition process for obtaining high quality, polycrystalline zinc ferrite thin films (ZFTF) on Si (100) and on CMOS-foundry-fabricated spiral inductor structures, rapidly, using safe solvents and precursors. An enhancement of up to 20% at 5 GHz in the inductance of a fabricated device was achieved due to the deposited ZFTF. Substantial inductance enhancement requires sufficiently thick films and our reported process is capable of depositing smooth, uniform films as thick as similar to 20 mu m just by altering the solution composition. The method is capable of depositing film conformally on a surface with complex geometry. As it requires neither a vacuum system nor any post-deposition processing, the method reported here has a low thermal budget, making it compatible with modern CMOS process flow.

Tuning ultrafast photoresponse of gold nanorods

Nondegenerate pump probe differential transmission experiments on gold nanorods with varying longitudinal surface plasmon resonance have revealed a new phenomenon where the polarity of the transient transmission signal can be reversibly switched between photo bleaching and photo-induced absorption by controlling probe fluence. Under the usual case where probe fluences are nominal, photo bleaching effect is observed for the nanorods with longitudinal surface plasmon resonance energy smaller than the probe photon energy. The laser-induced melting of the nanorods or change in their shape is ruled out for the observed optical switching effect. A quantitative understanding of the results is attempted by invoking a cascaded two-photon absorption dominant beyond a threshold probe fluence of similar to 75 mu J/cm(2).

Depth: a web server to compute depth, cavity sizes, detect potential small-molecule ligand-binding cavities and predict the pK(a) of ionizable residues in proteins

Residue depth accurately measures burial and parameterizes local protein environment. Depth is the distance of any atom/residue to the closest bulk water. We consider the non-bulk waters to occupy cavities, whose volumes are determined using a Voronoi procedure. Our estimation of cavity sizes is statistically superior to estimates made by CASTp and VOIDOO, and on par with McVol over a data set of 40 cavities. Our calculated cavity volumes correlated best with the experimentally determined destabilization of 34 mutants from five proteins. Some of the cavities identified are capable of binding small molecule ligands. In this study, we have enhanced our depth-based predictions of binding sites by including evolutionary information. We have demonstrated that on a database (LigASite) of similar to 200 proteins, we perform on par with ConCavity and better than MetaPocket 2.0. Our predictions, while less sensitive, are more specific and precise. Finally, we use depth (and other features) to predict pK(a)s of GLU, ASP, LYS and HIS residues. Our results produce an average error of just <1 pH unit over 60 predictions. Our simple empirical method is statistically on par with two and superior to three other methods while inferior to only one. The DEPTH server (http://mspc.bii.a-star.edu.sg/depth/) is an ideal tool for rapid yet accurate structural analyses of protein structures.

Dynamics of a flexible splitter plate in the wake of a circular cylinder

Rigid splitter plates in the wake of bluff bodies are known to suppress the primary vortex shedding. In the present work, we experimentally study the problem of a flexible splitter plate in the wake of a circular cylinder. In this case, the splitter plate is free to continuously deform along its length due to the fluid forces acting on it; the flexural rigidity (EI) of the plate being an important parameter. Direct visualizations of the splitter plate motions, for very low values of flexural rigidity (EI), indicate periodic traveling wave type deformations of the splitter plate with maximum tip amplitudes of the order of I cylinder diameter. As the Reynolds number based on cylinder diameter is varied, two regimes of periodic splitter plate motions are found that are referred to as mode I and mode II, with a regime of aperiodic motions between them. The frequency of plate motions in both periodic modes is found to be close to the plane cylinder Strouhal number of about 0.2, while the average frequencies in the non-periodic regime are substantially lower. The measured normalized phase speed of the traveling wave for both periodic modes is also close to the convection speed of vortices in the plane cylinder wake. As the flexural rigidity of the plate (EI) is increased, the response of the plate was found to shift to the right when plotted with flow speed or Re. To better capture the effect of varying EI, we define and use a non-dimensional bending stiffness, K*, similar to the ones used in the flag flutter problem, K*=EI/(0.5 rho(UL3)-L-2), where U is the free-stream velocity and L is the splitter plate length. Amplitude data for different EI cases when plotted against this parameter appear to collapse on to a single curve for a given splitter plate length. Measurements of the splitter plate motions for varying splitter plate lengths indicate that plates that are substantially larger than the formation length of the plane cylinder wake have similar responses, while shorter plates show significant differences.

Inhibition of Lactoperoxidase-Catalyzed Oxidation by Imidazole-Based Thiones and Selones: A Mechanistic Study

Herein, we describe the synthesis and biomimetic activity of a series of N,N-disubstituted thiones and selones that contain an imidazole pharmacophore. The N,N-disubstituted thiones do not show any inhibitory activity towards LPO-catalyzed oxidation reactions, but their corresponding N,N-disubstituted selones exhibit inhibitory activity towards LPO-catalyzed oxidation reactions. Substituents on the N atom of the imidazole ring appear to have a significant effect on the inhibition of LPO-catalyzed oxidation and iodination reactions. Selones 16, 17, and 19, which contain methyl, ethyl, and benzyl substituents, exhibit similar inhibition activities towards LPO-catalyzed oxidation reactions with IC50 values of 24.4, 22.5, and 22.5M, respectively. However, their activities are almost three-fold lower than that of the commonly used anti-thyroid drug methimazole (MMI). In contrast, selone 21, which contains a NCH2CH2OH substituent, exhibits high inhibitory activity, with an IC50 value of 7.2M, which is similar to that of MMI. The inhibitory activity of these selones towards LPO-catalyzed oxidation/iodination reactions is due to their ability to decrease the concentrations of the co-substrates (H2O2 and I2), either by catalytically reducing H2O2 (anti-oxidant activity) or by forming stable charge-transfer complexes with oxidized iodide species. The inhibition of LPO-catalyzed oxidation/iodination reactions by N,N-disubstituted selones can be reversed by increasing the concentration of H2O2. Interestingly, all of the N,N-disubstituted selones exhibit high anti-oxidant activities and their glutathione peroxidase (GPx)-like activity is 4-12-fold higher than that of the well-known GPx-mimic ebselen. These experimental and theoretical studies suggest that the selones exist as zwitterions, in which the imidazole ring contains a positive charge and the selenium atom carries a large negative charge. Therefore, the selenium moieties of these selones possess highly nucleophilic character. The 77SeNMR chemical shifts for the selones show large upfield shift, thus confirming the zwitterionic structure in solution.

Platinum Ion-Doped TiO2: High Catalytic Activity of Pt2+ with Oxide Ion Vacancy in Ti1-x4+Ptx2+O2-x Compared to Pt4+ without Oxide Ion Vacancy in Ti1-x4+Ptx4+O2

Ti0.97Pt0.032+O1.97 and Ti0.97Pt0.034+O2 have been synthesized by a solution combustion method using alanine and glycine as the fuels, respectively. Both crystallize in anatase TiO2 structure with 15 nm average crystallite size. X-ray photoelectron spectroscopy (XPS) confirmed Pt ions are in the 2+ state in Ti0.97Pt0.03O1.97 (alanine) and 4+ state in Ti0.97Pt0.03O2 (glycine). The rate of CO oxidation occurring over Ti0.97Pt0.032+O1.97 (0.76 mu mol.g(-1).s(-1)) is similar to 10, times more than that over Ti0.97Pt0.034+O2 at 60 degrees C (0.08 mu mol.g(-1).s(-1)). A large shift in 100% hydrocarbons conversion to lower temperature was observed for Pt2+ ion-substituted TiO2 relative 10 that for Pt4+ ion-substituted TiO2. After reoxidation of the reduced compound by H-2 as well as CO, Pt ions are stabilized in mixed valences, 2+ and 4+ states. The role of oxide ion vacancy has been demonstrated by CO oxidation and H-2 + O-2 recombination reactions in the presence and absence of O-2. We analyze the activated lattice oxygens upon substitution of Pt2+ and Pt4+ ions in TiO2, using first-principles density functional theory (DFT) calculations with supercells of Ti31Pt1O63, Ti30Pt2O62, and Ti29Pt3O61 for Pt2+ ion substitution and Ti31Pt1O64, Ti30Pt2O62, and Ti29Pt3O61 for Pt4+ ion substitution in TiO2. We find that the local structure of Pt2+ ion has a distorted square planar geometry and that of Pt4+ ion has an octahedral geometry similar to that of Ti4+ ion in pure TiO2. The change in coordination of Pt2+ ion gives rise to weakly bonded oxygens, and these oxygens are involved in high rates of catalytic reaction. Thus, the high catalytic activity results from synergistic roles of Pt2+ ion and oxide ion vacancy and weakly bonded lattice oxygen.