Analysis of the wave properties of a new two-lane continuum model with the coupling effect

A multilane extension of the single-lane anisotropic continuum model (GK model) developed by Gupta and Katiyar for traffic flow is discussed with the consideration of the coupling effect between the vehicles of different lanes in the instantaneous traffic situation and the lane-changing effect.The conditions for securing the linear stability of the new model are presented.The shock and the rarefaction waves,the local cluster effect and the phase transition are investigated through simulation experiments with the new model and are found to be consistent with the diverse nonlinear dynamical phenomena observed in a real traffic flow.The analysis also focuses on empirically observed twolane phenomena,such as lane usage inversion and the density dependence of the number of lane changes.It is shown that single-lane dynamics can be extended to multilane cases without changing the basic properties of the single-lane model.The results show that the new multilane model is capable of explaining some particular traffic phenomena and is in accordance with real traffic flow.     

Analyses of Lattice Traffic Flow Model on a Gradient Highway

The optimal current difference lattice hydrodynamic model is extended to investigate the traffic flow dynamics on a unidirectional single lane gradient highway. The effect of slope on uphill/downhill highway is examined through linear stability analysis and shown that the slope significantly affects the stability region on the phase diagram. Using nonlinear stability analysis, the Burgers, Korteweg-deVries (KdV) and modified Korteweg-deVries (mKdV) equations are derived in stable, metastable and unstable region, respectively. The effect of reaction coefficient is examined and concluded that it plays an important role in suppressing the traffic jams on a gradient highway. The theoretical findings have been verified through numerical simulation which confirm that the slope on a gradient highway significantly influence the traffic dynamics and traffic jam can be suppressed efficiently by considering the optimal current difference effect in the new lattice model.     

Luminescent proteins from Aequorea victoria: applications in drug discovery and in high throughput analysis

Recent progress in generating a vast number of drug targets through genomics and large compound libraries through combinatorial chemistry have stimulated advancements in drug discovery through the development of new high throughput screening (HTS) methods. Automation and HTS techniques are also highly desired in fields such as clinical diagnostics. Luminescence-based assays have emerged as an alternative to radiolabel-based assays in HTS as they approach the sensitivity of radioactive detection along with ease of operation, which makes them amenable to miniaturization. Luminescent proteins provide the advantage of reduced reagent and operating costs because they can be produced in unlimited amounts through the use of genetic engineering tools. In that regard, the use of two naturally occurring and recombinantly produced luminescent proteins from the jellyfish Aequorea victoria, namely, aequorin and the green fluorescent protein (GFP), has attracted attention in a number of analytical applications in diverse research areas. Aequorin is naturally bioluminescent and has therefore, virtually no associated background signal, which allows its detection down to attomole levels. GFP has become the reporter of choice in a variety of applications given that it is an autofluorescent protein that does not require addition of any co-factors for fluorescence emission. Furthermore, the generation of various mutants of GFP with differing luminescent and spectral properties has spurred additional interest in this protein. In this review, we focus on the use of aequorin and GFP in the development of highly sensitive assays that find applications in drug discovery and in high throughput analysis.     

2,2-Bis(3-allyl-4-hydroxyphenyl)hexafluoropropane and fluorosiloxane as coating materials for nerve agent sensors

A simpler technique for the synthesis of 2,2-bis(4-allyoxyphenyl)hexafluoropropane has been achieved from 4,4′-(hexafluoroisopropylidene)diphenol for obtaining 2,2-bis(3-allyl-4-hydroxyphenyl)hexafluoropropane. This monomer and its corresponding hybrid organic/inorganic siloxane polymer are successfully used as a coating material for the detection of toxic chemical warfare agents.     

Drug detection based on the conformational changes of calmodulin and the fluorescence of its enhanced green fluorescent protein fusion partner

A homogeneous phase protein-based assay for the high throughput screening of drugs was developed using enhanced green fluorescent protein (EGFP) as the reporter. For that, a fusion protein between calmodulin (CaM) and EGFP was constructed in order to monitor the conformational changes induced in CaM upon binding to tricyclic anti-depressant drugs. In the presence of Ca²⁺, CaM undergoes a conformational change exposing a hydrophobic pocket that interacts with CaM-binding proteins, peptides, and drugs. Further, the conformational changes induced in CaM upon binding to Ca²⁺ and the target analyte drug, leads to a change in the microenvironment of EGFP concomitant with a change in its fluorescence intensity. The observed change in fluorescence intensity of EGFP can be correlated to the concentration of the analyte present in the sample. Further, the response of CaM–EGFP fusion protein in the presence of Ca²⁺ to increasing concentrations of phenothiazines and structurally related tricyclic anti-depressants was investigated. Dose-response curves for various tricyclic anti-depressants were prepared. Moreover, this assay can serve as a model system for other homogeneous binding assays for pharmaceuticals employing genetically fused binding proteins with reporter proteins and may find applications in the high throughput screening of tricyclic anti-depressants.     

Enthalpy-entropy contributions to salt and osmolyte effects on molecular-scale hydrophobic hydration and interactions

Salts and additives can significantly affect the strength of water-mediated interactions in solution. We present results from molecular dynamics simulations focused on the thermodynamics of hydrophobic hydration, association, and the folding-unfolding of a hydrophobic polymer in water and in aqueous solutions of NaCl and of an osmolyte trimethylamine oxide (TMAO). It is known that addition of NaCl makes the hydration of hydrophobic solutes unfavorable and, correspondingly, strengthens their association at the pair as well as the many-body level (Ghosh, T.; Kalra, A.; Garde, S. J. Phys. Chem. B 2005, 109, 642), whereas the osmolyte TMAO has an almost negligible effect on the hydrophobic hydration and association (Athawale, M. V.; Dordick, J. S.; Garde, S. Biophys. J. 2005, 89, 858). Whether these effects are enthalpic or entropic in origin is not fully known. Here we perform temperature-dependent simulations to resolve the free energy into entropy and enthalpy contributions. We find that in TMAO solutions, there is an almost precise entropy-enthalpy compensation leading to the negligible effect of TMAO on hydrophobic phenomena. In contrast, in NaCl solutions, changes in enthalpy dominate, making the salt-induced strengthening of hydrophobic interactions enthalpic in origin. The resolution of total enthalpy into solute-solvent and solvent-solvent terms further shows that enthalpy changes originate primarily from solvent-solvent energy terms. Our results are consistent with experimental data on the hydration of small hydrophobic solutes by Ben-Naim and Yaacobi (Ben-Naim, A.; Yaacobi, M. J. Phys. Chem. 1974, 78, 170). In combination with recent work by Zangi, Hagen, and Berne (Zangi, R.; Hagen, M.; Berne, B. J. J. Am. Chem. Soc. 2007, 129, 4678) and the experimental data on surface tensions of salt solutions by Matubayasi et al. (Matubayasi, N.; Matsuo, H.; Yamamoto, K.; Yamaguchi, S.; Matuzawa, A. J. Colloid Interface Sci. 1999, 209, 398), our results highlight interesting length scale dependences of salt effects on hydrophobic phenomena. Although NaCl strengthens hydrophobic interactions at both small and large length scales, that effect is enthalpy-dominated at small length scales and entropy-dominated for large solutes and interfaces. Our results have implications for understanding of additive effects on water-mediated interactions, as well as on biocompatibility of osmolyte molecules in aqueous solutions.     

Molecular biosensing system based on intrinsically disordered proteins

Intrinsically disordered proteins (IDPs) that undergo structural transition upon binding their target molecules are becoming increasingly known. IDPs, because of their binding specificity and induced folding properties, can serve as biological recognition elements for sensing applications. In this paper, BRCA1, an IDP, was utilized as the biological recognition element to detect tumor suppressor protein p53 through the BRCA1/p53 binding interaction to serve as a proof-of-concept for the use of IDPs as recognition elements. The binding resulted in a disordered-to-ordered BRCA1 conformational change, as seen in our circular dichroism (CD) measurements. This conformational change in BRCA1 (residues 219-498) was utilized in the detection of p53 (residues 311-393) via both intrinsic and extrinsic fluorescent probes. Intrinsic tryptophan residues within the BRCA1 sequence detected p53 (311-393) with a detection limit of 0.559 nM (0.112 pmol). Two environmentally sensitive fluorophores, tetramethylrhodamine-5-maleimide (TMR) and 6-((5-dimethylaminonaphthalene-1-sulfonyl)amino)hexanoic acid, succinimidyl ester (dansyl-X, SE) were conjugated to BRCA1 (219-498). Dansyl-X, SE-conjugated BRCA1 (219-498) detected p53 (311-393) with a detection limit of 1.50 nM (0.300 pmol). The sensitivities for TMR and dansyl-X, SE-conjugated BRCA1 for the detection of p53 were nearly threefold and twofold higher, respectively, than the sensitivity reported using intrinsic BRCA1 tryptophan fluorescence. CD measurements did not reveal a disruption of p53/dye-conjugated BRCA1 binding, thus validating the applicability of environmentally sensitive fluorophores as transduction moieties to detect molecules which bind to IDPs and induce a structural change.     

Controlling the ON/OFF threading of a terpyridine containing [2]pseudorotaxane ligand via changes in coordination geometry

A 1,2-bis(pyridinium)ethane type axle containing a terpyridine chelate group, when combined with 24-membered crown ethers, forms [2]pseudorotaxanes, the stability of which can be controlled by coordination of metal ions with different geometries.