Generation and Analysis of Interaction Energy Maps of p-Substituted Benzoic Acid [(5-Nitro-thiophen-2-yl)-methylene]-Hydrazides Active against MRSA

In this preliminary study eighteen p-substituted benzoic acid [(5-nitro-thiophen-2-yl)-methylene]-hydrazides with antimicrobial activity were evaluated against multidrug-resistant Staphylococcus aureus, correlating the three-dimensional characteristics of the ligands with their respective bioactivities. The computer programs Sybyl and CORINA were used, respectively, for the design and three-dimensional conversion of the ligands. Molecular interaction fields were calculated using GRID program. Calculations using Volsurf resulted in a statistically consistent model with 48 structural descriptors showing that hydrophobicity is a fundamental property in the analyzed biological response.

Characterization of the stimulus for reactive oxygen species generation in calcium-overloaded mitochondria

We have used two different probes with distinct detection properties, dichlorodihydrofluorescein diacetate and Amplex Red/horseradish peroxidase, as well as different respiratory substrates and electron transport chain inhibitors, to characterize the reactive oxygen species (ROS) generation by the respiratory chain in calcium-overloaded mitochondria. Regardless of the respiratory substrate, calcium stimulated the mitochondrial generation of ROS, which were released at both the mitochondrial-matrix side and the extramitochondrial space, in a way insensitive to the mitochondrial permeability transition pores inhibitor cyclosporine A. In glutamate/malate-energized mitochondria, inhibition at complex I or complex III (ubiquinone cycle) similarly modulated ROS generation at either mitochondrial-matrix side or extramitochondrial space; this also occurred when the backflow of electrons to complex I in succinate-energized mitochondria was inhibited. On the other hand, in succinate-energized mitochondria the modulation of ROS generation at mitochondrial-matrix side or extra-mitochondrial space depends on the site of complex III which was inhibited. These results allow a straight comparison between the effects of different respiratory substrates and electron transport chain inhibitors on ROS generation at either mitochondrial-matrix side or extra-mitochondrial space in calcium-overloaded mitochondria.

A convergent approach for the generation of dendrimers containing the [Ru3O(CH3COO)(6)] electroactive core

We report on a convergent approach for the generation of dendrimers containing the [Ru3O(aC)(6)] electroactive core, of great interest as multielectron transfer catalysts. The proposed strategy is based on the generation of the trimeric complex [(Ru3O(ac)(6)(4-pic)(2)(pz))2-mu(2)-Ru3O(ac)(6)(CH3OH)](3+) (ac = acetate, 4-pic = 4-methylpyridine, pz = pyrazine). In this complex, the labile CH3OH ligand can be displaced by the bridging pyrazine ligand of [Ru3O(ac)(6)(pz)3](0), leading to the self-assembly of the [{[Ru3O(ac)(6)(4-pic)(2)(pz)](2)-mu(2)-Ru3O(ac)(6)(pz)}(3)- mu(3)-Ru3O(ac)(6)](n+) dendrimer containing 30 ruthenium atoms. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008).

Characterization of Rubus fruticosus mitochondria and salicylic acid inhibition of reactive oxygen species generation at Complex III/Q cycle: potential implications for hypersensitive response in plants

In addition to adenosine triphosphate (ATP) production, mitochondria have been implicated in the regulation of several physiological responses in plants, such as programmed cell death (PCD) activation. Salicylic acid (SA) and reactive oxygen species (ROS) are essential signaling molecules involved in such physiological responses; however, the mechanisms by which they act remain unknown. In non-photosynthesizing tissues, mitochondria appear to serve as the main source of ROS generation. Evidence suggests that SA and ROS could regulate plant PCD through a synergistic mechanism that involves mitochondria. Herein, we isolate and characterize the mitochondria from non-photosynthesizing cell suspension cultures of Rubus fruticosus. Furthermore, we assess the primary site of ROS generation and the effects of SA on isolated organelles. Mitochondrial Complex III was found to be the major source of ROS generation in this model. In addition, we discovered that SA inhibits the electron transport chain by inactivating the semiquinone radical during the Q cycle. Computational analyses confirmed the experimental data, and a mechanism for this action is proposed.

Bixin and lycopene modulation of free radical generation induced by cisplatin-DNA interaction

This work evaluated the Modulation of reactive oxygen species (ROS) produced by the cisplatin-human DNA interaction in a cell-free experimental model by the carotenoids bixin and lycopene extracted from, natural dietary Sources and purified through luminol- and Cypridina luciferin methoxy-analogue (MCLA)- enhanced chemiluminescence assays. The results showed that the ROS generation by DNA-cisplatin interaction was inhibited by both lycopene and bixin in a concentration-dependent manner. At a concentration of 100 mu M, lycopene and bixin inhibited Superoxide anion (O center dot(2)) generation at 90% and 82%, respectively, and the total ROS generation at 44% and 42%, respectively. The formation of significant amounts of isomers or degradation products of both carotenoids was not observed after ROS scavenging, as evaluated by high-performance liquid chromatography. Taken together, these results Suggest that carotenoids can be helpful to Modulate the oxidative stress found in cancer therapy with cisplatin. (c) 2008 Elsevier Ltd. All rights reserved.

Second floor reading area interior, Sunshine Coast University Library, Maroochydore

View of second floor reading area with rigid frames and air-conditioning ducting.

Second floor reading area interior, Sunshine Coast University Library, Maroochydore

View of second floor reading area with rigid frames and air-conditioning ducting.

Existence of Multiple Solutions for Second Order Boundary Value Problems

We give conditions on f involving pairs of lower and upper solutions which lead to the existence of at least three solutions of the two point boundary value problem y" + f(x, y, y') = 0, x epsilon [0, 1], y(0) = 0 = y(1). In the special case f(x, y, y') = f(y) greater than or equal to 0 we give growth conditions on f and apply our general result to show the existence of three positive solutions. We give an example showing this latter result is sharp. Our results extend those of Avery and of Lakshmikantham et al.

Molecular cocrystals of carboxylic acids. XXVII - An investigation into the use of triphenylphosphine oxide cocrystals for non-linear optics: the crystal structure of the adduct of triphenylphosphine oxide with N-methylpyrrole-2-carboxylic acid

Four adducts of triphenylphosphine oxide with aromatic carboxylic acids have been synthesized and tested for second-order non-linear optical properties. These were with N-methylpyrrole-2-carboxylic acid (I), indole-2-carboxylic acid (2), 3-dimethylaminobenzoic acid (3), and thiophen-2-carboxylic acid (4). Compound (1) produced clear, colourless crystals (space group P2(1)2(1)2(1) With a 9.892(1), b 14.033(1), c 15.305(1) Angstrom, Z 4) which allowed the structure to be determined by X-ray diffraction.

Sensitive detection of nitric oxide using seeded parametric four-wave mixing

A sensitive near-resonant four-wave mixing technique based on two-photon parametric four-wave mixing has been developed. Seeded parametric four-wave mixing requires only a single laser as an additional phase matched seeder field is generated via parametric four-wave mixing of the pump beam in a high gain cell. The seeder field travels collinearly with the pump beam providing efficient nondegenerate four-wave mixing in a second medium. This simple arrangement facilitates the detection of complex molecular spectra by simply scanning the pump laser. Seeded parametric four-wave mixing is demonstrated in both a low pressure cell and an air/acetylene flame with detection of the two-photon C (2) Pi(upsilon'=0)<--X (2) Pi(upsilon =0) spectrum of nitric oxide. From the cell data a detection limit of 10(12) molecules/cm(3) is established. A theoretical model of seeded parametric four-wave mixing is developed from existing parametric four-wave mixing theory. The addition of the seeder field significantly modifies the parametric four-wave mixing behaviour such that in the small signal regime, the signal intensity can readily be made to scale as the cube of the laser pump power while the density dependence follows a more familiar square law dependence, In general, we find excellent agreement between theory and experiment. Limitations to the process result from an ac Stark shift of the two-photon resonance in the high pressure seeder cell caused by the generation of a strong seeder field, as well as a reduction in phase matching efficiency due to the presence of certain buffer species. Various optimizations are suggested which should overcome these limitations, providing even greater detection sensitivity. (C) 1998 American Institute of Physics, [S0021-9606(98)01014-9].

Sensitive detection of sodium in a flame using parametric four-wave mixing and seeded parametric four-wave mixing

Two-photon resonant parametric four-wave mixing and a newly developed variant called seeded parametric four-wave mixing are used to detect trace quantities of sodium in a flame. Both techniques are simple, requiring only a single laser to generate a signal beam at a different wavelength which propagates collinearly with the pump beam, allowing efficient signal recovery. A comparison of the two techniques reveals that seeded parametric four-wave mixing is more than two orders of magnitude more sensitive than parametric four-wave mixing, with an estimated detection sensitivity of 5 x 10(9) atoms/cm(3). Seeded parametric four-wave mixing is achieved by cascading two parametric four-wave mixing media such that one of the parametric fields generated in the first high-density medium is then used to seed the same four-wave mixing process in a second medium in order to increase the four-wave mixing gain. The behavior of this seeded parametric four-wave mixing is described using semiclassical perturbation theory. A simplified small-signal theory is found to model most of the data satisfactorily. However, an anomalous saturationlike behavior is observed in the large signal regime. The full perturbation treatment, which includes the competition between two different four-wave mixing processes coupled via the signal field, accounts for this apparently anomalous behavior.

Prefrontal cortex involvement in selective letter generation: A functional magnetic resonance imaging study

Cerebral responses to alternating periods of a control task and a selective letter generation paradigm were investigated with functional Magnetic Resonance Imaging (fMRI). Subjects selectively generated letters from four designated sets of six letters from the English language alphabet, with the instruction that they were not to produce letters in alphabetical order either forward or backward, repeat or alternate letters. Performance during this condition was compared with that of a control condition in which subjects recited the same letters in alphabetical order. Analyses revealed significant and extensive foci of activation in a number of cerebral regions including mid-dorsolateral frontal cortex, inferior frontal gyrus, precuneus, supramarginal gyrus, and cerebellum during the selective letter generation condition. These findings are discussed with respect to recent positron emission tomography (PET) and fMRI studies of verbal working memory and encoding/retrieval in episodic memory.

Subcycling first- and second-order generalizations of the trapezoidal rule

Subcycling algorithms which employ multiple timesteps have been previously proposed for explicit direct integration of first- and second-order systems of equations arising in finite element analysis, as well as for integration using explicit/implicit partitions of a model. The author has recently extended this work to implicit/implicit multi-timestep partitions of both first- and second-order systems. In this paper, improved algorithms for multi-timestep implicit integration are introduced, that overcome some weaknesses of those proposed previously. In particular, in the second-order case, improved stability is obtained. Some of the energy conservation properties of the Newmark family of algorithms are shown to be preserved in the new multi-timestep extensions of the Newmark method. In the first-order case, the generalized trapezoidal rule is extended to multiple timesteps, in a simple way that permits an implicit/implicit partition. Explicit special cases of the present algorithms exist. These are compared to algorithms proposed previously. (C) 1998 John Wiley & Sons, Ltd.

Folding, calcium binding, and structural characterization of a concatemer of the first and second ligand-binding modules of the low-density lipoprotein receptor

The ligand-binding domain of the low-density lipoprotein (LDL) receptor is comprised of seven tandemly repeated ligand-binding modules, each being approximately 40 amino acids long and containing six conserved cysteine residues. We have expressed and characterized a concatemer of the first two modules (LB1 and LB2) of the human LDL receptor. Oxidative folding of the recombinant concatemer (rLB(1-2)), in the presence of calcium ions, gave a single dominant isomer with six disulfide bonds. Peptic cleavage of the short Linker region that connects the last cysteine residue of LB1 and the first cysteine residue of LB2 yielded two discrete fragments, thus excluding the presence of intermodule disulfide bonds. The N-terminal module, LB1, reacted with a conformation-specific monoclonal antibody (IgG-C7) made to LB1 in the native LDL receptor. From this, we concluded that the first module was correctly folded, with the same set of disulfide bonds as LB1 of the LDL receptor. The disulfide bond connections of LB2 were identified from mass spectral analysis of fragments formed by digestion of the C-terminal peptic fragment with elastase. These data showed that the disulfide bonds of LB2 connected Cys(I) and Cys(III), Cys(II) and Cys(V), and Cys(IV) and Cys(VI). This pattern is identical to that found for recombinant LB1 and LB2. The concatemer has two high-affinity calcium-binding sites, one per module. An analysis of the secondary chemical shifts of C alpha protons shows that the conformations of LB1 and LB2 in the concatemer are very similar to those of the individual modules, with no evidence for strong interactions between the two modules.

Three-dimensional quantum solitons with parametric coupling

We consider the quantum field theory of two bosonic fields interacting via both parametric (cubic) and quartic couplings. In the case of photonic fields in a nonlinear optical medium, this corresponds to the process of second-harmonic generation (via chi((2)) nonlinearity) modified by the chi((3)) nonlinearity. The quantum solitons or energy eigenstates (bound-state solutions) are obtained exactly in the simplest case of two-particle binding, in one, two, and three space dimensions. We also investigate three-particle binding in one space dimension. The results indicate that the exact quantum solitons of this field theory have a singular, pointlike structure in two and three dimensions-even though the corresponding classical theory is nonsingular. To estimate the physically accessible radii and binding energies of the bound states, we impose a momentum cutoff on the nonlinear couplings. In the case of nonlinear optical interactions, the resulting radii and binding energies of these photonic particlelike excitations in highly nonlinear parametric media appear to be close to physically observable values.