Monte Carlo simulation of light transport in turbid medium with embedded object-spherical, cylindrical, ellipsoidal, or cuboidal objects embedded within multilayered tissues

Monte Carlo modeling of light transport in multilayered tissue (MCML) is modified to incorporate objects of various shapes (sphere, ellipsoid, cylinder, or cuboid) with a refractive-index mismatched boundary. These geometries would be useful for modeling lymph nodes, tumors, blood vessels, capillaries, bones, the head, and other body parts. Mesh-based Monte Carlo (MMC) has also been used to compare the results from the MCML with embedded objects (MCML-EO). Our simulation assumes a realistic tissue model and can also handle the transmission/reflection at the object-tissue boundary due to the mismatch of the refractive index. Simulation of MCML-EO takes a few seconds, whereas MMC takes nearly an hour for the same geometry and optical properties. Contour plots of fluence distribution from MCML-EO and MMC correlate well. This study assists one to decide on the tool to use for modeling light propagation in biological tissue with objects of regular shapes embedded in it. For irregular inhomogeneity in the model (tissue), MMC has to be used. If the embedded objects (inhomogeneity) are of regular geometry (shapes), then MCML-EO is a better option, as simulations like Raman scattering, fluorescent imaging, and optical coherence tomography are currently possible only with MCML. (C) 2014 Society of Photo-Optical Instrumentation Engineers (SPIE)

Differentially Selective Chemosensor with Fluorescence Off-On Responses on Cu2+ and Zn2+ Ions in Aqueous Media and Applications in Pyrophosphate Sensing, Live Cell Imaging, and Cytotoxicity

A new benzoyl hydrazone based chemosensor R is synthesized by Schiff base condensation of 2,6-diformyl-4-methylphenol and phenyl carbohydrazide and acts as a highly selective fluorescence sensor for Cu2+ and Zn2+ ions in aqueous media. The reaction of R with CuCl2 or ZnCl2 forms the corresponding dimeric dicopper(II) Cu-2(R)(CH3O)-(NO3)](2)(CH3O)(2) (R-Cu2+) and dizinc(1) Zn-2(R)(2)](NO3)(2) (R-Zn2+) complexes, which are characterized, as R, by conventional techniques including single-crystal X-ray analysis. Electronic absorption and fluorescence titration studies of R with different metal cations in a CH3CN/0.02 M HEPES buffer medium (pH = 7.3) show a highly selective binding affinity only toward Cu(2+)and Zn2+ ions even in the presence of other commonly coexisting ions such as Ne+, K+, Mg2+, Ca2+, Mn2+, Fe2+, Fe3+, Co2+, Ni2+, Cd2+, and Hg2+. Quantification of the fluorescence titration analysis shows that the chemosensor R can indicate the presence of Cu2+ and Zn2+ even at very low concentrations of 17.3 and 16.5 ppb, respectively. R-Zn2+ acts as a selective metal-based fluorescent sensor for inorganic pyrophosphate ion (PPi) even in the presence of other common anions such as F-, Cl-, Br-, I-, CH3COO-, CO32-, HCO3-, N-3(-), SO42-, PPi, AMP, ADP, and ATP in an aqueous medium. The propensity of R as a bioimaging fluorescent probe to detect Cu2+ and Zn2+ ions in human cervical HeLa cancer cell lines and their cytotoxicity against human cervical (HeLa), breast cancer (MCF7), and noncancer breast epithelial (MCF10a) cells have also been investigated. R-Cu2+ shows better cytotoxicity and sensitivity toward cancer cells over noncancer cells than R and R-Zn2+ under identical conditions, with the appearance of apoptotic bodies.

Fine-Tuning Dual Emission and Aggregation-Induced Emission Switching in NPI-BODIPY Dyads

Three new NPI-BODIPY dyads 1-3 (NPI = 1,8-naphthalimide, BODIPY = boron-dipyrromethene) were synthesized, characterized, and studied. The NPI and BODIPY moieties in these dyads are electronically separated by oxoaryl bridges, and the compounds only differ structurally with respect to methyl substituents on the BODIPY fluorophore. The NPI and BODIPY moieties retain their optical features in molecular dyads 1-3. Dyads 1-3 show dual emission in solution originating from the two separate fluorescent units. The variations of the dual emission in these compounds are controlled by the structural flexibilities of the systems. Dyads 13, depending on their molecular flexibilities, show considerably different spectral shapes and dissimilar intensity ratios of the two emission bands. The dyads also show significant aggregation-induced emission switching (AIES) on formation of nano-aggregates in THF/H2O with changes in emission color from green to red. Whereas the flexible and aggregation-prone compound 1 shows AIES, rigid systems with less favorable intermolecular interactions (i.e., 2 and 3) show aggregation-induced quenching of emission. Correlations of the emission intensity and structural flexibility were found to be reversed in solution and aggregated states. Photophysical and structural investigations suggested that intermolecular interactions (e. g., pi-pi stacking) play a major role in controlling the emission of these compounds in the aggregated state.

Useful approach to the synthesis of aryl thio- and selenoglycosides in the presence of rongalite

A simple, mild, and cost effective methodology has been developed for the synthesis of aryl thio-and selenoglycosides from glycosyl halides and diaryl dichalcogenides. Diaryl dichalcogenides undergo reductive cleavage in the presence of rongalite (HOCH2SO2Na) to generate a chalcogenide anion in situ followed by reaction with glycosyl halides to furnish the corresponding aryl thio- and selenoglycosides in excellent yields. Using this protocol, synthesis of 4-methyl-7-thioumbelliferyl-beta-D-cellobioside (MUS-CB), a fluorescent non-hydrolyzable substrate analogue for cellulases has been achieved. (C) 2014 Elsevier Ltd. All rights reserved.

A napthelene-pyrazol conjugate: Al(III) ion-selective blue shifting chemosensor applicable as biomarker in aqueous solution

A newly synthesized and crystalographically characterized napthelene-pyrazol conjugate, 1-(5-phenyl-1H-pyrazole-3-ylimino)-methyl]-naphthalen-2-ol (HL) behaves as an Al(III) ion-selective chemosensor through internal charge transfer (ICT)-chelation-enhanced fluorescence (CHEF) processes in 100 mM HEPES buffer (water-DMSO 5 : 1, v/v) at biological pH with almost no interference of other competitive ions. This mechanism is readily studied from electronic, fluorimetric and H-1 NMR titration. The probe (HL) behaved as a highly selective fluorescent sensor for Al(III) ions as low as 31.78 nM within a very short response time (15-20 s). The sensor (HL), which has no cytotoxicity, is also efficient in detecting the distribution of Al(III) ions in HeLa cells via image development under fluorescence microscope.

Explosives Sensing by Using Electron-Rich Supramolecular Polymers: Role of Intermolecular Hydrogen Bonding in Significant Enhancement of Sensitivity

We demonstrate here that supramolecular interactions enhance the sensitivity towards detection of electron-deficient nitro-aromatic compounds (NACs) over discrete analogues. NACs are the most commonly used explosive ingredients and are common constituents of many unexploded landmines used during World WarII. In this study, we have synthesised a series of pyrene-based polycarboxylic acids along with their corresponding discrete esters. Due to the electron richness and the fluorescent behaviour of the pyrene moiety, all the compounds act as sensors for electron-deficient NACs through a fluorescence quenching mechanism. A Stern-Volmer quenching constant determination revealed that the carboxylic acids are more sensitive than the corresponding esters towards NACs in solution. The high sensitivity of the acids was attributed to supramolecular polymer formation through hydrogen bonding in the case of the acids, and the enhancement mechanism is based on an exciton energy migration upon excitation along the hydrogen-bond backbone. The presence of intermolecular hydrogen bonding in the acids in solution was established by solvent-dependent fluorescence studies and dynamic light scattering (DLS) experiments. In addition, the importance of intermolecular hydrogen bonds in solid-state sensing was further explored by scanning tunnelling microscopy (STM) experiments at the liquid-solid interface, in which structures of self-assembled monolayer of the acids and the corresponding esters were compared. The sensitivity tests revealed that these supramolecular sensors can even detect picric acid and trinitrotoluene in solution at levels as low as parts per trillion (ppt), which is much below the recommended permissible level of these constituents in drinking water.

Noise Detected NMR Spectroscopy

Spin noise phenomenon was predicted way back in 1946. However, experimental investigations regarding spin noise became possible only recently with major technological improvements in NMR hardware. These experiments have several potential novel applications and also demand refinements in the existing theoretical framework to explain the phenomenon. Elegance of noise spectroscopy in gathering information about the properties of a system lies in the fact that it does not require external perturbation, and the system remains in thermal equilibrium. Spin noise is intrinsic magnetic fluctuations, and both longitudinal and transverse components have been detected independently in many systems. Detection of fluctuating longitudinal magnetization leads to field of Magnetic Resonance Force Microscopy (MRFM) that can efficiently probe very few spins even down to the level of single spin utilizing ultrasensitive cantilevers. Transverse component of spin noise, which can simultaneously monitor different resonances over a given frequency range enabling one to distinguish between different chemical environments, has also received considerable attention, and found many novel applications. These experiments demand a detailed understanding of the underlying spin noise phenomenon in order to perform perturbation-free magnetic resonance and widen the highly promising application area. Detailed investigations of noise magnetization have been performed recently using force microscopy on equilibrium ensemble of paramagnetic alkali atoms. It was observed that random fluctuations generate spontaneous spin coherences which has similar characteristics as generated by macroscopic magnetization of polarized ensemble in terms of precession and relaxation properties. Several other intrinsic properties like g-factors, isotope-abundance ratios, hyperfine splitting, spin coherence lifetimes etc. also have been achieved without having to excite the sample. In contrast to MRFM-approaches, detection of transverse spin noise also offers novel applications, attracting considerable attention. This has unique advantage as different resonances over a given frequency range enable one to distinguish between different chemical environments. Since these noise signatures scale inversely with sample size, these approaches lead to the possibility of non-perturbative magnetic resonance of small systems down to nano-scale. In this review, these different approaches will be highlighted with main emphasis on transverse spin noise investigations.

A quinazoline derivative as quick-response red-shifted reporter for nanomolar Al3+ and applicable to living cell staining

A newly synthesized and structurally characterized quinazoline derivative (L) has been shown to act as a quick-response chemosensor for Al3+ with a high selectivity over other metal ions in water-DMSO. In the presence of Al3+, L shows a red-shifted ratiometric enhancement in fluorescence as a result of internal charge transfer and chelation-enhanced fluorescence through the inhibition of a photo-induced electron transfer mechanism. This probe detects Al3+ at concentrations as low as 1.48 nM in 100 mM HEPES buffer (DMSO-water, 1 : 9 v/v) at biological pH with a very short response time (15-20 s). L was applied to biological imaging to validate its utility as a fluorescent probe for monitoring Al3+ ions in living cells, illustrating its value in practical environmental and biological systems.

Effect of alkyl substituents in BODIPYs: a comparative DFT computational investigation

Random changes in the alkyl substitution patterns of fluorescent dyes, e.g. BODIPYs, are often accompanied by significant changes in their photophysical properties. To understand such alterations in properties in closely related molecular systems, a comparative DFT (density functional theory) computational investigation was performed in order to comprehend the effects of alkyl substitution in controlling the structural and electronic nature of BODIPY dyes. In this context, a systematic strategy was utilized, considering all possible outcomes of constitutionally-isomeric molecules to understand the alkyl groups' effects on the BODIPY molecules. Four different computational methods {i.e. B3LYP/631G(d); B3LYP/6-311++ G(d,p); wb97xd/6-311++ G(d,p) and mpw1pw91/6-311++ G(d,p)} were employed to rationalize the agreement of the trends associated with the molecular properties. In line with experimental observations, it was found that alkyl substituents in BODIPY dyes situated at 3/5-positions effectively participate in stabilization as well as planarization of such molecules. Screening of all the possible isomeric molecular systems was used to understand the individual properties and overall effects of the typical alkyl substituents in controlling several basic properties of such BODIPY molecules.

Carbon quantum dots as a macromolecular crowder

Fluorescent carbon quantum dots (CQD) induce macromolecular crowding making them suitable for probing the structure, function and dynamics of both hydrophilic and hydrophobic peptides/proteins under near in-cell conditions.

Layer-by-Layer Assembly of Nafion on Surlyn with Ultrahigh Water Vapor Barrier

A layer-by-layer approach was used for the fabrication of multilayer films for ultra high gas barrier applications. The ultra high gas barrier material was designed by incorporating Nafion layer in between bilayers of poly(ethylene imine) and poly(acrylic acid) on a Surlyn substrate. When the barrier film with self-assembled Nafion is exposed to the moist environment, Nafion absorbs and desorbs water molecules simultaneously, thereby reducing the ingress of moisture in to the film. In order to study the effect of Nafion, the fabricated barrier materials with and without the presence of Nafion were tested for water vapor barrier properties. The barrier films were further used for encapsulating organic photovoltaic devices and were evaluated for their potential use in barrier applications. The devices encapsulated with the films containing Nafion exhibited better performance when subjected to accelerated aging conditions. Therefore, this study demonstrates the effectiveness of self-assembled Nafion in reducing the water vapor permeability by nearly five orders of magnitude and in increasing the lifetimes of organic devices by similar to 22 times under accelerated weathering conditions.

Measuring Glutathione Redox Potential of HIV-1-infected Macrophages

Redox signaling plays a crucial role in the pathogenesis of human immunodeficiency virus type-1 (HIV-1). The majority of HIV redox research relies on measuring redox stress using invasive technologies, which are unreliable and do not provide information about the contributions of subcellular compartments. A major technological leap emerges from the development of genetically encoded redox-sensitive green fluorescent proteins (roGFPs), which provide sensitive and compartment-specific insights into redox homeostasis. Here, we exploited a roGFP-based specific bioprobe of glutathione redox potential (E-GSH; Grx1-roGFP2) and measured subcellular changes in E-GSH during various phases of HIV-1 infection using U1 monocytic cells (latently infected U937 cells with HIV-1). We show that although U937 and U1 cells demonstrate significantly reduced cytosolic and mitochondrial E-GSH (approximately -310 mV), active viral replication induces substantial oxidative stress (E-GSH more than -240 mV). Furthermore, exposure to a physiologically relevant oxidant, hydrogen peroxide (H2O2), induces significant deviations in subcellular E-GSH between U937 and U1, which distinctly modulates susceptibility to apoptosis. Using Grx1-roGFP2, we demonstrate that a marginal increase of about similar to 25 mV in E-GSH is sufficient to switch HIV-1 from latency to reactivation, raising the possibility of purging HIV-1 by redox modulators without triggering detrimental changes in cellular physiology. Importantly, we show that bioactive lipids synthesized by clinical drug-resistant isolates of Mycobacterium tuberculosis reactivate HIV-1 through modulation of intracellular E-GSH. Finally, the expression analysis of U1 and patient peripheral blood mononuclear cells demonstrated a major recalibration of cellular redox homeostatic pathways during persistence and active replication of HIV.

Actin-Curcumin Interaction: Insights into the Mechanism of Actin Polymerization Inhibition

Curcumin, derived from rhizomes of the Curcuma longa plant, is known to possess a wide range of medicinal properties. We have examined the interaction of curcumin with actin and determined their binding and thermodynamic parameters using isothermal titration calorimetry. Curcumin is weakly fluorescent in aqueous solution, and binding to actin enhances fluorescence several fold with a large blue shift in the emission maximum. Curcumin inhibits microfilament formation, which is similar to its role in inhibiting microtubule formation. We synthesized a series of stable curcumin analogues to examine their affinity for actin and their ability to inhibit actin self-assembly. Results show that curcumin is a ligand with two symmetrical halves, each of which possesses no activity individually. Oxazole, pyrazole, and acetyl derivatives are less effective than curcumin at inhibiting actin self-assembly, whereas a benzylidiene derivative is more effective. Cell biology studies suggest that disorganization of the actin network leads to destabilization of filaments in the presence of curcumin. Molecular docking reveals that curcumin binds close to the cytochalasin binding site of actin. Further molecular dynamics studies reveal a possible allosteric effect in which curcumin binding at the barbed end of actin is transmitted to the pointed end, where conformational changes disrupt interactions with the adjacent actin monomer to interrupt filament formation. Finally, the recognition and binding of actin by curcumin is yet another example of its unique ability to target multiple receptors.

Maximum likelihood analysis of multi-stress accelerated life test data of series systems with competing log-normal causes of failure

This article presents frequentist inference of accelerated life test data of series systems with independent log-normal component lifetimes. The means of the component log-lifetimes are assumed to depend on the stress variables through a linear stress translation function that can accommodate the standard stress translation functions in the literature. An expectation-maximization algorithm is developed to obtain the maximum likelihood estimates of model parameters. The maximum likelihood estimates are then further refined by bootstrap, which is also used to infer about the component and system reliability metrics at usage stresses. The developed methodology is illustrated by analyzing a real as well as a simulated dataset. A simulation study is also carried out to judge the effectiveness of the bootstrap. It is found that in this model, application of bootstrap results in significant improvement over the simple maximum likelihood estimates.

Electron-Rich Triphenylamine-Based Sensors for Picric Acid Detection

This paper demonstrates the role of solvent in selectivity and sensitivity of a series of electron-rich compounds for the detection of trace amounts of picric acid. Two new electron-rich fluorescent esters (6, 7) containing a triphenylamine backbone as well as their analogous carboxylic acids (8, 9) have been synthesized and characterized. Fluorescent triphenylamine coupled with an ethynyl moiety constitutes p-electron-rich selective and sensitive probes for electron-deficient picric acid (PA). In solution, the high sensitivity of all the sensors toward PA can be attributed to a combined effect of the ground-state charge-transfer complex formation and resonance energy transfer between the sensor and analyte. The acids 8 and 9 also showed enhanced sensitivity for nitroaromatics in the solid state, and their enhanced sensitivity could be attributed to exciton migration due to close proximity of the neighboring acid molecules, as evident from the X-ray diffraction study. The compounds were found to be quite sensitive for the detection of trace amount of nitroaromatics in solution, solid, and contact mode.