Fluorescent probe studies of biomembranes and model systems. The design and use of anionic site reporters

The fluorescence properties of a homologous series of fluorescent alkylamines are described. The binding of the probes to crythrocyte membranes increases with the length of the alkyl chain. The probes are shown to interact more strongly with membranes than with protein and lipid model systems. The binding of the probes to the membrane is sensitive to the cation concentration of the medium.

Agents Based Algorithms for Design Parameter Estimation in Contaminant Transport Inverse Problems

A considerable amount of work has been dedicated on the development of analytical solutions for flow of chemical contaminants through soils. Most of the analytical solutions for complex transport problems are closed-form series solutions. The convergence of these solutions depends on the eigen values obtained from a corresponding transcendental equation. Thus, the difficulty in obtaining exact solutions from analytical models encourages the use of numerical solutions for the parameter estimation even though, the later models are computationally expensive. In this paper a combination of two swarm intelligence based algorithms are used for accurate estimation of design transport parameters from the closed-form analytical solutions. Estimation of eigen values from a transcendental equation is treated as a multimodal discontinuous function optimization problem. The eigen values are estimated using an algorithm derived based on glowworm swarm strategy. Parameter estimation of the inverse problem is handled using standard PSO algorithm. Integration of these two algorithms enables an accurate estimation of design parameters using closed-form analytical solutions. The present solver is applied to a real world inverse problem in environmental engineering. The inverse model based on swarm intelligence techniques is validated and the accuracy in parameter estimation is shown. The proposed solver quickly estimates the design parameters with a great precision.

Cooperative game play with avatars and agents: Differences in brain activity and the experience of play

The current study sought to identify the impact of whether teammates in a cooperative videogame were controlled by other humans (avatars) or by the game (agents). The impact on player experience was explored through both subjective questionnaire measures and brain wave activity measurement (electroencephalography). Play with human teammates was associated with a greater sense of relatedness, but less competence and flow than play with other computer-controlled teammates. In terms of brain activity, play with human teammates was associated with greater activity in the alpha, theta and beta power bands than play with computer-controlled teammates. Overall, the results suggest that play with human teammates involves greater cognitive activity in terms of 'mentalising' than play with computer-controlled teammates. Additionally, the associations between subjective measures of player experience and brain activity are described. Limitations of the current study are identified and key directions for future research are discussed.

Design, synthesis, and application of novel triclosan prodrugs as potential antimalarial and antibacterial agents

A number of new triclosan-conjugated analogs bearing biodegradable ester linkage have been synthesized, characterized and evaluated for their antimalarial and antibacterial activities. Many of these compounds exhibit good inhibition against Plasmodium falciparum and Escherichia coli. Among them tertiary amine containing triclosan-conjugated prodrug (5) inhibited both P. falciparum (IC50; 0.62 μM) and E. coli (IC50; 0.26 μM) at lower concentrations as compared to triclosan. Owing to the presence of a cleavable ester moiety, these new prodrugs are hydrolyzed under physiological conditions and parent molecule, triclosan, is released. Further, introduction of tertiary/quaternary functionality increases their cellular uptake. These properties impart them with higher potency to their antimalarial as well as antibacterial activities. The best compound among them 5 shows close to four-fold enhanced activities against P. falciparum and E. coli cultures as compared to triclosan.

Fluorescent Fields: electric lighting and the rationalization of the modern corporate workplace

This study investigates the implications of the introduction of electric lighting systems, building technologies, and theories of worker efficiency on the deep spatial and environmental transformations that occurred within the corporate workplace during the twentieth century. Examining the shift from daylighting strategies to largely artificially lit workplace environments, this paper argues that electric lighting significantly contributed to the architectural rationalization of both office work and the modern office environment. Contesting the historical and critical marginalization of lighting within the discourse of the modern built environment, this study calls for a reassessment of the role of artificial lighting in the development of the modern corporate workplace. Keywords: daylighting, fluorescent lighting, rationalization, workplace design

Self-Assembly of a Nanoscopic Prism via a New Organometallic Pt3 Acceptor and Its Fluorescent Detection of Nitroaromatics

A nanoscale-sized cage with a trigonal prismatic shape is prepared by coordination-driven self-assembly of a predesigned organometallic Pt-3 acceptor with an organic clip-type ligand. This trigonal prism is fluorescent and undergoes efficient fluorescence quenching by nitroaromatics, which are the chemical signatures of many explosives.

Synthesis and exploration of novel curcumin analogues as anti-malarial agents

Curcumin, a major yellow pigment and active component of turmeric, has been shown to possess anti-inflammatory and anti-cancer activities. Recent studies have indicated that curcumin inhibits chloroquine-sensitive (CQ-S) and chloroquine-resistant (CQ-R) Plasmodium falciparum growth in culture with an IC50 of not, vert, similar3.25 μM (MIC = 13.2 μM) and IC50 4.21 μM (MIC = 14.4 μM), respectively. In order to expand their potential as anti-malarials a series of novel curcumin derivatives were synthesized and evaluated for their ability to inhibit P. falciparum growth in culture. Several curcumin analogues examined show more effective inhibition of P. falciparumgrowth than curcumin. The most potent curcumin compounds 3, 6, and 11 were inhibitory for CQ-S P. falciparum at IC50 of 0.48, 0.87, 0.92 μM and CQ-R P. falciparum at IC50 of 0.45 μM, 0.89, 0.75 μM, respectively. Pyrazole analogue of curcumin (3) exhibited sevenfold higher anti-malarial potency against CQ-S and ninefold higher anti-malarial potency against CQ-R. Curcumin analogues described here represent a novel class of highly selective P. falciparum inhibitors and promising candidates for the design of novel anti-malarial agents.

Understanding the folding process of synthetic polymers by small-molecule folding agents

Two acceptor containing polyimides PDI and NDI carrying pyromellitic diimide units and 1,4,5,8-naphthalene tetracarboxy diimide units, respectively, along with hexa(oxyethylene) (EO6) segments as linkers, were prepared from the corresponding dianhydrides and diamines. These polyimides were made to fold by interaction with specifically designed folding agents containing a dialkoxynaphtha-lene (DAN) donor linked to a carboxylic acid group. The alkali-metal counter-ion of the donor carboxylic acid upon complexation with the EO6 segment brings the DAN unit in the right location to induce a charge-transfer complex formation with acceptor units in the polymer backbone. This two-point interaction between the folding agent and the polymer backbone leads to a folding of the polymer chain, which was readily monitored by NMR titrations. The effect of various parameters, such as structures of the folding agent and polymer, and the solvent composition, on the folding propensities of the polymer was studied.

Synergistic effects of UdgB and Ung in mutation prevention and protection against commonly encountered DNA damaging agents in Mycobacterium smegmatis

The incorporation of dUMP during replication or the deamination of cytosine in DNA results in the occurrence of uracils in genomes. To maintain genomic integrity, uracil DNA glycosylases (UDGs) excise uracil from DNA and initiate the base-excision repair pathway. Here, we cloned, purified and biochemically characterized a family 5 UDG, UdgB, from Mycobacterium smegmatis to allow us to use it as a model organism to investigate the physiological significance of the novel enzyme. Studies with knockout strains showed that compared with the wild-type parent, the mutation rate of the udgB(-) strain was approximately twofold higher, whereas the mutation rate of a strain deficient in the family 1 UDG (ung(-)) was found to be similar to 8.4-fold higher. Interestingly, the mutation rate of the double-knockout (ung(-)ludgB(-)) strain was remarkably high, at similar to 19.6-fold. While CG to TA mutations predominated in the ung(-) and ung(-)/udgb(-) strains, AT to GC mutations were enhanced in the udgB(-) strain. The ung(-)/udgB(-) strain was notably more sensitive to acidified nitrite and hydrogen peroxide stresses compared with the single knockouts (ung(-) or udgB(-)). These observations reveal a synergistic effect of UdgB and Ung in DNA repair, and could have implications for the generation of attenuated strains of Mycobacterium tuberculosis.

Fluorescent resonant excitation energy transfer in linear polyenes

We have studied the dynamics of excitation transfer between two conjugated polyene molecules whose intermolecular separation is comparable to the molecular dimensions. We have employed a correlated electron model that includes both the charge-charge, charge-bond, and bond-bond intermolecular electron repulsion integrals. We have shown that the excitation transfer rate varies as inverse square of donor-acceptor separation R-2 rather than as R-6, suggested by the Foumlrster type of dipolar approximation. Our time-evolution study alsom shows that the orientational dependence on excitation transfer at a fixed short donor-acceptor separation cannot be explained by Foumlrster type of dipolar approximation beyond a certain orientational angle of rotation of an acceptor polyene with respect to the donor polyene. The actual excitation transfer rate beyond a certain orientational angle is faster than the Foumlrster type of dipolar approximation rate. We have also studied the excitation transfer process in a pair of push-pull polyenes for different push-pull strengths. We have seen that, depending on the push-pull strength, excitation transfer could occur to other dipole coupled states. Our study also allows for the excitation energy transfer to optically dark states which are excluded by Foumlrster theory since the one-photon transition intensity to these states (from the ground state) is zero.

Analysis of the binding of polymyxin B to endotoxic lipid A and core glycolipid using a fluorescent displacement probe

Dansylcadaverine, a cationic fluorescent probe binds to bacterial lipopolysaccharide and lipid A, and is displaced competitively by other compounds which possess affinity toward endotoxins. The binding parameters of dansylcadaverine for lipid A were determined by Scatchard analysis to be two apparently equivalent sites with apparent dissociation constants (Kd) ranging between 16 μM to 26 μM, while that obtained for core glycolipid from Salmonella minnesota Re595 yielded a Kd of 22 μM to 28 μM with three binding sites. The Kd of polymyxin B for lipid A was computed from dansylcadaverine displacement by the method of Horovitz and Levitzki (Horovitz, A., and Levitzki, A. (1987) Proc. Natl. Acad. Sci. USA 84, 6654–6658). The applicability of this method for analyzing fluorescence data was validated by comparing the Kds of melittin for lipid A obtained by direct Scatchard analysis, and by the Horovitz-Levitzki method. The displacement of dansylcadaverine from lipid A by polymyxin B was distinctly biphasic with Kds for polymyxin B-lipid A interactions corresponding to 0.4 μM and 1.5 μM, probably resulting as a consequence of lipid A being a mixture of mono- and di-phosphoryl species. This was not observed with core glycolipid, for which the Kd for polymyxin was estimated to range from 1.1 μM to 5.8 μM. The use of dansylcadaverine as a displacement probe offers a novel and convenient method of quantitating the interactions of a wide variety of substances with lipid A.

Synthesis and exploration of novel curcumin analogues as anti-malarial agents

Curcumin, a major yellow pigment and active component of turmeric, has been shown to possess anti-inflammatory and anti-cancer activities. Recent studies have indicated that curcumin inhibits chloroquine-sensitive (CQ-S) and chloroquine-resistant (CQ-R) Plasmodium falciparum growth in culture with an IC50 of similar to 3.25 mu M (MIC = 13.2 mu M) and IC50 4.21 mu M (MIC = 14.4 mu M), respectively. In order to expand their potential as anti-malarials a series of novel curcumin derivatives were synthesized and evaluated for their ability to inhibit P. falciparum growth in culture. Several curcumin analogues examined show more effective inhibition of P. falciparum growth than curcumin. The most potent curcumin compounds 3, 6, and 11 were inhibitory for CQ-S P. falciparum at IC50 of 0.48, 0.87, 0.92 mu M and CQ-R P. falcipartan at IC50 of 0.45 mu M, 0.89, 0.75 mu M, respectively. Pyrazole analogue of curcumin (3) exhibited sevenfold higher anti-malarial potency against CQ-S and ninefold higher anti-malarial potency against CQ-R. Curcumin analogues described here represent a novel class of highly selective P. falcipartan inhibitors and promising candidates for the design of novel anti-malarial agents. (C) 2007 Elsevier Ltd. All rights reserved.