Trehalose-6-Phosphate as a Potential Lead Candidate for the Development of Tps1 Inhibitors: Insights from the Trehalose Biosynthesis Pathway in Diverse Yeast Species

In some pathogens, trehalose biosynthesis is induced in response to stress as a protection mechanism. This pathway is an attractive target for antimicrobials as neither the enzymes, Tps1, and Tps2, nor is trehalose present in humans. Accumulation of T6P in Candida albicans, achieved by deletion of TPS2, resulted in strong reduction of fungal virulence. In this work, the effect of T6P on Tps1 activity was evaluated. Saccharomyces cerevisiae, C. albicans, and Candida tropicalis were used as experimental models. As expected, a heat stress induced both trehalose accumulation and increased Tps1 activity. However, the addition of 125 μM T6P to extracts obtained from stressed cells totally abolished or reduced in 50 and 60 % the induction of Tps1 activity in S. cerevisiae, C. tropicalis, and C. albicans, respectively. According to our results, T6P is an uncompetitive inhibitor of S. cerevisiae Tps1. This kind of inhibitor is able to decrease the rate of reaction to zero at increased concentrations. Based on the similarities found in sequence and function between Tps1 of S. cerevisiae and some pathogens and on the inhibitory effect of T6P on Tps1 activity observed in vitro, novel drugs can be developed for the treatment of infectious diseases caused by organisms whose infectivity and survival on the host depend on trehalose.     

Thermodynamic study of 1,2,3-triphenylbenzene and 1,3,5-triphenylbenzene

The energetic study of 1,2,3-triphenylbenzene (1,2,3-TPhB) and 1,3,5-triphenylbenzene (1,3,5-TPhB) isomers was carried out by making use of the mini-bomb combustion calorimetry and Knudsen mass-loss effusion techniques. The mini-bomb combustion calorimetry technique was used to derive the standard (p° = 0.1 MPa) molar enthalpies of formation in the crystalline state from the measured standard molar energies of combustion for both isomers. The Knudsen mass-loss effusion technique was used to measure the dependence with the temperature of the vapour pressure of crystalline 1,2,3-TPhB, which allowed the derivation of the standard molar enthalpy of sublimation, by application of the Clausius–Clapeyron equation. The sublimation study of 1,3,5-TPhB had been performed previously. From the combination of data obtained by both techniques, the standard molar enthalpies of formation in the gaseous state, for both isomers, at T = 298.15 K, were calculated. The results indicate a higher stability of the 1,3,5-TPhB isomer relative to 1,2,3-TPhB, similarly to the terphenyls. Nevertheless, the 1,2,3-TPhB isomer is not as energetically destabilized as one might expect, supporting the existence of a π–π displacive stacking interaction between both pairs of outer phenyl rings. The volatility difference between the two isomers is ruled by the enthalpy of sublimation. The volatility of the 1,2,3-TPhB is two orders of magnitude higher than the 1,3,5-TPhB isomer, at T = 298.15 K.     

93.

pH effect on the photochemistry of 4-methylcoumarin phosphate esters: caged-phosphate case study     

Pinheiro AV  Parola AJ  Baptista PV  Lima JC 《The journal of physical chemistry. A》2010,114(49):12795-12803

There are numerous reports of coumarin ester derivatives, in particular phosphate esters, as photocleavable cages in biological systems. Despite the comprehensive analysis of the photocleavage mechanism, studies of 4-methylcoumarin caged phosphates and/or nucleotides were always performed at constant pH. In this work, we present the study of the pH effect on the photochemistry of (7-diethylaminocoumarin-4-yl)methyl phosphate (DEACM-P). Fluorescence and photocleavage quantum yields, as well as the fluorescence decay times were measured as a function of the pH. It was found that the pH produces significant changes in the overall photochemical quantum yield of DEACM-P, and the observed changes are complementary to those obtained from the fluorescence quantum yield. Deprotonation of DEACM-HPO(4)(-) to yield DEACM-PO(4)(2-), produces a decrease in the photochemical quantum yield (from 0.0045 to 0.0003) and an increase in the fluorescence quantum yield (from 0.072 to 0.092). Moreover, from the analysis of the decay times, we have also found that hydroxyl ion is not only relevant, but it is mechanistically involved in the photoreaction of DEACM-HPO(4)(-).     

94.

Yet another proof of Marstrand’s theorem     

Yuri Lima  Carlos Gustavo Moreira 《Bulletin of the Brazilian Mathematical Society》2011,42(2):331-345

In a paper from 1954 Marstrand proved that if K ⊂ ℝ² is a Borel set with Hausdorff dimension greater than 1, then its one-dimensional projection has positive Lebesgue measure for almost-all directions. In this article, we give a combinatorial proof of this theorem, extending the techniques developed in our previous paper [9].     

95.

Multimode vibrational couplings in resonant positron annihilation     

d'A Sanchez S  Lima MA  Varella MT 《Physical review letters》2011,107(10):103201

The mechanisms for multimode vibrational couplings in resonant positron annihilation are not well understood. We show that these resonances can arise from positron-induced distortions of the potential energy surface (target response to the positron field). Though these distortions can transfer energy into single- and multiquantum vibrations, they have so far been disregarded as a pathway to resonant annihilation. We also compare the existing annihilation theories and show that the currently accepted model can be cast as a special case of the Feshbach annihilation theory.     

96.

3D elemental distribution images in biological samples by XRFµCT     

G. R. Pereira  H. S. Rocha  C. Calza  M. J. Anjos  I. Lima  C. A. Pérez  R. T. Lopes 《X射线光谱测定》2011,40(4):260-264

An X‐ray transmission microtomography (CT) system combined with an X‐ray fluorescence microtomography (XRFµCT) system was implemented in the Brazilian Synchrotron Light Laboratory (LNLS), Campinas, Brazil. The aim of this work was to determine the elemental distribution in biological samples (breast, prostate and lung samples) in order to verify the concentration of some elements correlated with characteristics and pathology of each tissue observed by the transmission CT. The experiments were performed at the X‐ray fluorescence beamline (D09B‐XRF) of the Brazilian Synchrotron Light Laboratory, Campinas, Brazil. A quasi‐monochromatic beam produced by a multilayer monochromator was used as an incident beam. The sample was placed on a high‐precision goniometer and translation stages that allow rotating as well as translating it perpendicularly to the beam. The fluorescence photons were collected with an energy dispersive HPGe detector placed at 90° to the incident beam, while transmitted photons were detected with a fast Na(Tl) scintillation counter placed behind the sample on the beam path. The CT images were reconstructed using a filtered‐back projection algorithm and the XRFµCT images were reconstructed using a filtered‐back projection algorithm with absorption corrections. The 3D images were reconstructed using the 3D‐DOCTOR software. Results from the 3D visualization showed that the distribution of iron, copper and zinc is different and heterogeneous from the analyzed samples. Copyright © 2011 John Wiley & Sons, Ltd.     

97.

Majority-vote model on triangular, honeycomb and Kagomé lattices     

J.C. SantosF.W.S. Lima  K. Malarz 《Physica A》2011,390(2):359-364

     

98.

A computational analysis of multidimensional piecewise-linear models with applications to oil production optimization     

Thiago Lima Silva  Eduardo Camponogara 《European Journal of Operational Research》2014

Production optimization of gas-lifted oil wells under facility, routing and pressure constraints is a challenging problem, which has attracted the interest of operations engineers aiming to drive economic gains and scientists for its inherent complexity. The hardness of this problem rests on the non-linear characteristics of the multidimensional well-production and pressure-drop functions, as well as the discrete routing decisions. To this end, this work develops several formulations in Mixed-Integer Linear Programming (MILP) using multidimensional piecewise-linear models to approximate the non-linear functions with domains spliced in hypercubes and simplexes. Computational and simulation analyses were performed considering a synthetic but realistic oil field modeled with a multiphase-flow simulator. The purpose of the analyses was to assess the relative performance of the MILP formulations and their impact on the simulated oil production.     

99.

On the umbilicity of complete constant mean curvature spacelike hypersurfaces     

Cícero P. Aquino  Henrique F. de Lima 《Mathematische Annalen》2014,360(3-4):555-569

In this paper, we show that a complete spacelike hypersurface immersed with constant mean curvature either in the de Sitter space or in the anti-de Sitter space must be totally umbilical, provided that its Gauss mapping has some suitable behavior. In particular, we use an extension of Hopf’s maximum principle due to Yau in order to give new positive answers to Goddard’s conjecture.     

100.

Uniqueness of complete spacelike hypersurfaces via their higher order mean curvatures in a conformally stationary spacetime          下载免费PDF全文

Henrique Fernandes de Lima  Marco Antonio Lázaro Velásquez 《Mathematische Nachrichten》2014,287(11-12):1223-1240

We study complete noncompact spacelike hypersurfaces immersed into conformally stationary spacetimes, that is, Lorentzian manifolds endowed with a timelike conformal vector field V. In this setting, by using as main analytical tool a suitable maximum principle for complete noncompact Riemannian manifolds, we establish new characterizations of totally umbilical hypersurfaces in terms of their higher order mean curvatures. For instance, supposing an appropriated restriction on the norm of the tangential component of the vector field V, we are able to show that such hypersurfaces must be totally umbilical provided that either some of their higher order mean curvatures are linearly related or one of them is constant. Applications to the so‐called generalized Robertson‐Walker spacetimes are given. In particular, we extend to the Lorentzian context a classical result due to Jellett  29 .     

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pH effect on the photochemistry of 4-methylcoumarin phosphate esters: caged-phosphate case study

There are numerous reports of coumarin ester derivatives, in particular phosphate esters, as photocleavable cages in biological systems. Despite the comprehensive analysis of the photocleavage mechanism, studies of 4-methylcoumarin caged phosphates and/or nucleotides were always performed at constant pH. In this work, we present the study of the pH effect on the photochemistry of (7-diethylaminocoumarin-4-yl)methyl phosphate (DEACM-P). Fluorescence and photocleavage quantum yields, as well as the fluorescence decay times were measured as a function of the pH. It was found that the pH produces significant changes in the overall photochemical quantum yield of DEACM-P, and the observed changes are complementary to those obtained from the fluorescence quantum yield. Deprotonation of DEACM-HPO(4)(-) to yield DEACM-PO(4)(2-), produces a decrease in the photochemical quantum yield (from 0.0045 to 0.0003) and an increase in the fluorescence quantum yield (from 0.072 to 0.092). Moreover, from the analysis of the decay times, we have also found that hydroxyl ion is not only relevant, but it is mechanistically involved in the photoreaction of DEACM-HPO(4)(-).     

Yet another proof of Marstrand’s theorem

In a paper from 1954 Marstrand proved that if K ⊂ ℝ² is a Borel set with Hausdorff dimension greater than 1, then its one-dimensional projection has positive Lebesgue measure for almost-all directions. In this article, we give a combinatorial proof of this theorem, extending the techniques developed in our previous paper [9].     

Multimode vibrational couplings in resonant positron annihilation

The mechanisms for multimode vibrational couplings in resonant positron annihilation are not well understood. We show that these resonances can arise from positron-induced distortions of the potential energy surface (target response to the positron field). Though these distortions can transfer energy into single- and multiquantum vibrations, they have so far been disregarded as a pathway to resonant annihilation. We also compare the existing annihilation theories and show that the currently accepted model can be cast as a special case of the Feshbach annihilation theory.     

3D elemental distribution images in biological samples by XRFµCT

An X‐ray transmission microtomography (CT) system combined with an X‐ray fluorescence microtomography (XRFµCT) system was implemented in the Brazilian Synchrotron Light Laboratory (LNLS), Campinas, Brazil. The aim of this work was to determine the elemental distribution in biological samples (breast, prostate and lung samples) in order to verify the concentration of some elements correlated with characteristics and pathology of each tissue observed by the transmission CT. The experiments were performed at the X‐ray fluorescence beamline (D09B‐XRF) of the Brazilian Synchrotron Light Laboratory, Campinas, Brazil. A quasi‐monochromatic beam produced by a multilayer monochromator was used as an incident beam. The sample was placed on a high‐precision goniometer and translation stages that allow rotating as well as translating it perpendicularly to the beam. The fluorescence photons were collected with an energy dispersive HPGe detector placed at 90° to the incident beam, while transmitted photons were detected with a fast Na(Tl) scintillation counter placed behind the sample on the beam path. The CT images were reconstructed using a filtered‐back projection algorithm and the XRFµCT images were reconstructed using a filtered‐back projection algorithm with absorption corrections. The 3D images were reconstructed using the 3D‐DOCTOR software. Results from the 3D visualization showed that the distribution of iron, copper and zinc is different and heterogeneous from the analyzed samples. Copyright © 2011 John Wiley & Sons, Ltd.     

A computational analysis of multidimensional piecewise-linear models with applications to oil production optimization

Production optimization of gas-lifted oil wells under facility, routing and pressure constraints is a challenging problem, which has attracted the interest of operations engineers aiming to drive economic gains and scientists for its inherent complexity. The hardness of this problem rests on the non-linear characteristics of the multidimensional well-production and pressure-drop functions, as well as the discrete routing decisions. To this end, this work develops several formulations in Mixed-Integer Linear Programming (MILP) using multidimensional piecewise-linear models to approximate the non-linear functions with domains spliced in hypercubes and simplexes. Computational and simulation analyses were performed considering a synthetic but realistic oil field modeled with a multiphase-flow simulator. The purpose of the analyses was to assess the relative performance of the MILP formulations and their impact on the simulated oil production.     

On the umbilicity of complete constant mean curvature spacelike hypersurfaces

In this paper, we show that a complete spacelike hypersurface immersed with constant mean curvature either in the de Sitter space or in the anti-de Sitter space must be totally umbilical, provided that its Gauss mapping has some suitable behavior. In particular, we use an extension of Hopf’s maximum principle due to Yau in order to give new positive answers to Goddard’s conjecture.     

Uniqueness of complete spacelike hypersurfaces via their higher order mean curvatures in a conformally stationary spacetime

We study complete noncompact spacelike hypersurfaces immersed into conformally stationary spacetimes, that is, Lorentzian manifolds endowed with a timelike conformal vector field V. In this setting, by using as main analytical tool a suitable maximum principle for complete noncompact Riemannian manifolds, we establish new characterizations of totally umbilical hypersurfaces in terms of their higher order mean curvatures. For instance, supposing an appropriated restriction on the norm of the tangential component of the vector field V, we are able to show that such hypersurfaces must be totally umbilical provided that either some of their higher order mean curvatures are linearly related or one of them is constant. Applications to the so‐called generalized Robertson‐Walker spacetimes are given. In particular, we extend to the Lorentzian context a classical result due to Jellett  29 .