alpha-Tocopherol derived lipid dimers as efficient gene transfection agents. Mechanistic insights into lipoplex internalization and therapeutic induction of apoptotic activity

In this report, we present cationic dimeric (gemini) lipids for significant plasmid DNA (pDNA) delivery to different cell lines without any marked toxicity in the presence of serum. Six gemini lipids based on alpha-tocopherol were synthesized, which differed in their spacer chain lengths. Each of these gemini lipids mixed with a helper lipid, 1,2-dioleoyl phosphatidyl ethanolamine (DOPE), was capable of forming stable aqueous suspensions. These co-liposomal systems were examined for their potential to transfect pEGFP-C3 plasmid DNA into nine cell lines of different origins. The transfection efficacies noticed in terms of EGFP expression levels using flow cytometry were well corroborated using independent fluorescence microscopy studies. Significant EGFP expression levels were reported using the gemini co-liposomes, which counted significantly better than one well known commercial formulation, Lipofectamine 2000 (L2 K). Transfection efficacies were also analyzed in terms of the degree of intracellular delivery of labeled plasmid DNA (pDNA) using confocal microscopy, which revealed an efficient internalization in the presence of serum. The cell viability assays performed using optimized formulations demonstrated no significant toxicity towards any of the cell lines used in the study. We also had a look at the lipoplex internalization pathway to profile the uptake characteristics. A caveolae/lipid raft route was attributed to their excellent gene transfection capabilities. The study was further advanced by using a therapeutic p53-EGFP-C3 plasmid and the apoptotic activity was observed using FACS and growth inhibition assay.

Synthesis of cadmium oxide and carbon nanotube based nanocomposites and their use as a sensing interface for xanthine detection

Xanthine oxidase (XOD) extracted from bovine milk was immobilized covalently via N-ethyl-N'-(3-dimethylaminopropyl) carbodiimide (EDC) and N-hydroxy succinimide (NHS) chemistry onto cadmium oxide nanoparticles (CdO)/carboxylated multiwalled carbon nanotube (c-MWCNT) composite film electrodeposited on the surface of an Au electrode. The nanocomposite modified Au electrode was characterized by Fourier transform infrared (FTIR), cyclic voltammetry (CV), scanning electron microscopy (SEM) and electrochemical impedance spectroscopy (EIS) before and after immobilization of XOD. Under optimal operation conditions (25 degrees C, + 0.2 V vs. Ag/AgCl, sodium phosphate buffer, pH 7.5), the following characteristics are attributed to the biosensor: linearity of response up to xanthine concentrations of 120 mu M, detection limit of 0.05 mu M (S/N = 3) and a response time of at most 4 s. After being used 100 times over a period of 120 days, only 50% loss of the initial activity of the biosensor was evaluated when stored at 4 degrees C. The fabricated biosensor was successfully employed for the determination of xanthine in fish meat.

Ag2S sensitized mesoporous Bi2WO6 architectures with enhanced visible light photocatalytic activity and recycling properties

To harvest solar energy more efficiently, novel Ag2S/Bi2WO6 heterojunctions were synthesized by a hydrothermal route. This novel photocatalyst was synthesized by impregnating Ag2S into a Bi2WO6 semiconductor by a hydrothermal route without any surfactants or templates. The as prepared structures were characterized by multiple techniques such as X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), Brunauer-Emmet-Teller (BET) analysis, scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy dispersive X-ray spectrometry (EDS), UV-vis diffuse reflection spectroscopy (DRS) and photoluminescence (PL). The characterization results suggest mesoporous hierarchical spherical structures with a high surface area and improved photo response in the visible spectrum. Compared to bare Bi2WO6, Ag2S/Bi2WO6 exhibited much higher photocatalytic activity towards the degradation of dye Rhodamine B (RhB). Although silver based catalysts are easily eroded by photogenerated holes, the Ag2S/Bi2WO6 photocatalyst was found to be highly stable in the cyclic experiments. Based on the results of BET, Pl and DRS analysis, two possible reasons have been proposed for the enhanced visible light activity and stability of this novel photocatalyst: (1) broadening of the photoabsorption range and (2) efficient separation of photoinduced charge carriers which does not allow the photoexcited electrons to accumulate on the conduction band of Ag2S and hence prevents the photocorrosion.

Robust Whisper Activity Detection Using Long-Term Log Energy Variation of Sub-Band Signal

The goal in the whisper activity detection (WAD) is to find the whispered speech segments in a given noisy recording of whispered speech. Since whispering lacks the periodic glottal excitation, it resembles an unvoiced speech. This noise-like nature of the whispered speech makes WAD a more challenging task compared to a typical voice activity detection (VAD) problem. In this paper, we propose a feature based on the long term variation of the logarithm of the short-time sub-band signal energy for WAD. We also propose an automatic sub-band selection algorithm to maximally discriminate noisy whisper from noise. Experiments with eight noise types in four different signal-to-noise ratio (SNR) conditions show that, for most of the noises, the performance of the proposed WAD scheme is significantly better than that of the existing VAD schemes and whisper detection schemes when used for WAD.

A quantitative imaging-based screen reveals the exocyst as a network hub connecting endocytosis and exocytosis

The coupling of endocytosis and exocytosis underlies fundamental biological processes ranging from fertilization to neuronal activity and cellular polarity. However, the mechanisms governing the spatial organization of endocytosis and exocytosis require clarification. Using a quantitative imaging-based screen in budding yeast, we identified 89 mutants displaying defects in the localization of either one or both pathways. High-resolution single-vesicle tracking revealed that the endocytic and exocytic mutants she4 Delta and bud6 Delta alter post-Golgi vesicle dynamics in opposite ways. The endocytic and exocytic pathways display strong interdependence during polarity establishment while being more independent during polarity maintenance. Systems analysis identified the exocyst complex as a key network hub, rich in genetic interactions with endocytic and exocytic components. Exocyst mutants displayed altered endocytic and post-Golgi vesicle dynamics and interspersed endocytic and exocytic domains compared with control cells. These data are consistent with an important role for the exocyst in coordinating endocytosis and exocytosis.

Metal Complexes of Curcumin for Cellular Imaging, Targeting, and Photoinduced Anticancer Activity

CONSPECTUS: Curcumin is a polyphenolic species. As an active ingredient of turmeric, it is well-known for its traditional medicinal properties. The therapeutic values include antioxidant, anti-inflammatory, antiseptic, and anticancer activity with the last being primarily due to inhibition of the transcription factor NF-kappa B besides affecting several biological pathways to arrest tumor growth and its progression. Curcumin with all these positive qualities has only remained a potential candidate for cancer treatment over the years without seeing any proper usage because of its hydrolytic instability involving the diketo moiety in a cellular medium and its poor bioavailability. The situation has changed considerably in recent years with the observation that curcumin in monoanionic form could be stabilized on binding to a metal ion. The reports from our group and other groups have shown that curcumin in the metal-bound form retains its therapeutic potential. This has opened up new avenues to develop curcumin-based metal complexes as anticancer agents. Zinc(II) complexes of curcumin are shown to be stable in a cellular medium. They display moderate cytotoxicity against prostate cancer and neuroblastoma cell lines. A similar stabilization and cytotoxic effect is reported for (arene)ruthenium(II) complexes of curcumin against a variety of cell lines. The half-sandwich 1,3,5-triaza-7-phosphatricyclo-3.3.1.1]decane (RAPTA)-type ruthenium(II) complexes of curcumin are shown to be promising cytotoxic agents with low micromolar concentrations for a series of cancer cell lines. In a different approach, cobalt(III) complexes of curcumin are used for its cellular delivery in hypoxic tumor cells using intracellular agents that reduce the metal and release curcumin as a cytotoxin. Utilizing the photophysical and photochemical properties of the curcumin dye, we have designed and synthesized photoactive curcumin metal complexes that are used for cellular imaging by fluorescence microscopy and damaging the cancer cells on photoactivation in visible light while being minimally toxic in darkness. In this Account, we have made an attempt to review the current status of the chemistry of metal curcumin complexes and present results from our recent studies on curcumin complexes showing remarkable in vitro photocytotoxicity. The undesirable dark toxicity of the complexes can be reduced with suitable choice of the metal and the ancillary ligands in a ternary structure. The complexes can be directed to specific subcellular organelles. Selectivity by targeting cancer cells over normal cells can be achieved with suitable ligand design. We expect that this methodology is likely to provide an impetus toward developing curcumin-based photochemotherapeutics for anticancer treatment and cure.

Activity-travel behaviour of non-workers from Bangalore City in India

This paper presents exploratory and statistical analyses of the activity-travel behaviour of non-workers in Bangalore city in India. The study summarises the socio-demographic characteristics as well as the activity-travel behaviour of non-workers using a primary activity-travel survey data collected by the authors. Where possible, the research also compares the analysis findings with the case studies on activity-travel behaviour of non-workers, carried out in developed and developing countries. This gives an opportunity to understand the differences/similarities in the activity-travel behaviour of non-workers across diverse socio-cultural settings. The preliminary exploratory analysis shed light on the differences in activity participation, trip chaining, time-of-day preference for trip departure, and mode use behaviour of non-workers in Bangalore city. Statistical models were developed for investigating the effects of individual and household socio-demographics, land use parameters, and travel context attributes on activity participation, trip chaining, time-of-day choice, and mode choice decisions of non-workers. A few important results of the analysis are the influence of viewing television at home on out-of-home activity participation and trip-chaining behaviour, and the impact of in-home maintenance activity duration on time-of-day choice. Further, based on the findings of the initial analyses, an attempt has been made in this study to develop an integrated model that links time allocation, time-of-day choice, and trip chaining behaviour of non-workers. The study also discusses the implications of the research findings for transportation planning and policy for Bangalore city. (C) 2015 Elsevier Ltd. All rights reserved.

High Catalytic Activity of Amorphous Ir-Pi for Oxygen Evolution Reaction

Large-scale production of hydrogen gas by water electrolysis is hindered by the sluggish kinetics of oxygen evolution reaction (OER) at the anode. The development of a highly active and stable catalyst for OER is a challenging task. Electrochemically prepared amorphous metal-based catalysts have gained wide attention after the recent discovery of a cnbalt-phosphate (Co-Pi) catalyst: Herein, an amorphous iridium-phosphate (Ir-Pi) is investigated as an oxygen evolution catalyst. The catalyst is prepared by the anodic polarization of carbon paper electrodes in neutral phosphate buffer solutions containing IrCl3. The Ir-Pi film deposited on the substrate has significant amounts of phosphate and It centers in an oxidation state higher than +4. Phosphate plays a significant role in the deposition of the catalyst and also in its activity toward OER. The onset potential of OER on the Ir-Pi is about 150 mV lower in comparison with the Co-Pi under identical experimental conditions. Thus, Ir-Pi is a promising catalyst for electrochemical oxidation of water.

Introduction of a catalytic triad increases the glutathione peroxidase-like activity of diaryl diselenides

Reactive oxygen species (ROS)-mediated diseased states are of major concern in modern day life. Under oxidative stress conditions, the cellular antioxidants deplete, leading to several biological disorders. Small molecule mimics of different antioxidant enzymes are found to be useful in supplementing the biological systems to detoxify ROS. In this study, we have synthesized a series of amine or amide-based diselenides containing an additional amino group as glutathione peroxidase (GPx) mimetics. These diselenides act as a catalytic triad model of the native GPx featuring two basic amino groups near the selenium centre. A comparison of the catalytic activities reveals that the additional amino group increases the activity significantly in the presence of aromatic thiols. Deprotonation of thiol by an additional amine either stabilizes the selenolate intermediate or facilitates the nucleophilic attack of thiol in other intermediates. The Se-77 NMR experiments and DFT calculations show that the amino group does not have any significant effect on the catalytic intermediates. Although the amino moiety increases the nucleophilicity of the thiol, it does not prevent the thiol exchange reactions that take place in the selenenyl sulfide intermediates.

Novel AgBr/Ag3PO4 Decorated Ceria Nanoflake Composites for Enhanced Photocatalytic Activity toward Dyes and Bacteria under Visible Light

The aim of this study was to develop heterogeneous visible light active photocatalysts using AgBr and Ag3PO4 using CeO2 nanoflakes as an efficient substrate. Ascorbic acid was employed as a fuel to synthesize fine ceria nanoflakes by a facile solution combustion process. AgBr and Ag3PO4 were decorated on ceria to prepare AgBr/Ag3PO4/ceria nanocomposites. The structure of the composite was determined by X-ray diffraction analysis. Novel flakelike morphology was revealed using electron microscopy techniques. The nanocomposites exhibit excellent photocatalytic activity under visible light compared to pristine ceria nanoparticles. The nanocomposite catalyst particles degraded both anionic and cationic dyes. It also exhibited efficient antimicrobial activity under visible light. The AgBr/Ag3PO4/ceria nanocomposite was characterized using X-ray diffraction analysis, diffuse reflectance spectroscopy, electron microscopy, BET surface area analysis, and X-ray photoelectron spectroscopy, and the reasons for enhanced photocatalytic activity were elucidated. The presence of silver based semiconductors on ceria has shown to decrease charge recombination through photoluminescence analysis that attributed for enhanced photocatalytic activity. The AgBr/Ag3PO4/ceria nanocomposite has shown a stable performance after many repeated cycles.

New symmetrical dinucleating ligand based assembly of bridged dicopper(II) and dizinc(II) centers: Synthesis, structure, spectroscopy, magnetic properties and glycoside hydrolysis

Two dinuclear copper(II) complexes Li(H2O)(3)(CH3OH)](4)Cu2Br4]Cu-2(cpdp)(mu-O2CCH3)](4)(OH)(2) (1), Cu (H2O)(4)]Cu-2(cpdp)(mu-O2CC6H5)](2)Cl-2 center dot 5H(2)O (2), and a dinuclear zinc(II) complex Zn-2(cpdp)(mu-O2CCH3)] (3) have been synthesized using pyridine and benzoate functionality based new symmetrical dinucleating ligand, N, N'-Bis2-carboxybenzomethyl]-N, N'-Bis2-pyridylmethyl]-1,3-diaminopropan-2-ol (H(3)cpdp). Complexes 1, 2 and 3 have been synthesized by carrying out reaction of the ligand H3cpdp with stoichiometric amounts of Cu-2(O2CCH3)(4)(H2O)(2)], CuCl2 center dot 2H(2)O/C6H5COONa, and Zn(CH3COO)(2)center dot 2H(2)O, respectively, in methanol in the presence of NaOH at ambient temperature. Characterizations of the complexes have been done using various analytical techniques including single crystal X-ray structure determination. The X-ray crystal structure analyses reveal that the copper(II) ions in complexes 1 and 2 are in a distorted square pyramidal geometry with Cu-Cu separation of 3.455(8) angstrom and 3.492(1)angstrom, respectively. The DFT optimized structure of complex 3 indicates that two zinc(II) ions are in a distorted square pyramidal geometry with Zn-Zn separation of 3.492(8)angstrom. UV-Vis and mass spectrometric analyses of the complexes confirm their dimeric nature in solution. Furthermore, H-1 and C-13 NMR spectroscopic investigations authenticate the integrity of complex 3 in solution. Variable-temperature (2-300 K) magnetic susceptibility measurements show the presence of antiferromagnetic interactions between the copper centers, with J = -26.0 cm(-1) and -23.9 cm(-1) ((H) over cap = -2JS(1)S(2)) in complexes 1 and 2, respectively. In addition, glycosidase-like activity of the complexes has been investigated in aqueous solution at pH similar to 10.5 by UV-Vis spectrophotometric technique using p-nitrophenyl-alpha-D-glucopyranoside (4) and p-nitrophenyl-beta-D-glucopyranoside (5) as model substrates. (C) 2015 Elsevier B.V. All rights reserved.

Tungsten-based nanomaterials (WO3 & Bi2WO6): Modifications related to charge carrier transfer mechanisms and photocatalytic applications

Heterogeneous photocatalysis is an ideal green energy technology for the purification of wastewater. Although titania dominates as the reference photocatalyst, its wide band gap is a bottleneck for extended utility. Thus, search for non-TiO2 based nanomaterials has become an active area of research in recent years. In this regard, visible light absorbing polycrystalline WO3 (2.4-2.8 eV) and Bi2WO6 (2.8 eV) with versatile structure-electronic properties has gained considerable interest to promote the photocatalytic reactions. These materials are also explored in selective functional group transformation in organic reactions, because of low reduction and oxidation potential of WO3 CB and Bi2WO6 VB, respectively. In this focused review, various strategies such as foreign ion doping, noble metal deposition and heterostructuring with other semiconductors designed for efficient photocatalysis is discussed. These modifications not only extend the optical response to longer wavelengths, but also prolong the life-time of the charge carriers and strengthen the photocatalyst stability. The changes in the surface-bulk properties and the charge carrier transfer dynamics associated with each modification correlating to the high activity are emphasized. The presence of oxidizing agents, surface modification with Cu2+ ions and synthesis of exposed facets to promote the degradation rate is highlighted. In depth study on these nanomaterials is likely to sustain interest in wastewater remediation and envisaged to signify in various green energy applications. (C) 2015 Elsevier B.V. All rights reserved.

Design and administration of activity-travel diaries: a case study from Bengaluru city in India

Studies on travel survey instrument design and administration in the context of Indian cities are limited despite the fact that these aspects of travel survey face unique challenges here when compared to the cities in the developed world. Here we report results of a pilot survey conducted for evaluating the performances, alternative diary formats and survey administration techniques in Bengaluru city, India. The study proposes two diary formats. `Diary-1' is in day-planner format and is a variant of the one reported earlier in the literature. `Diary-2' is derived as a combination of `Diary-1' and the trip-based diaries widely applied in Indian cities. `Face-to-face', and `drop-off and pick-up' methods of survey administration are considered for retrieving the activity-travel information of individuals. Evidence appears to be strong that diary-2 is preferable to diary-1 for collecting the travel details of individuals. The comparison of the retrieval methods suggests that the face-to-face method of instrument administration is superior to the drop-off and pick-up method in terms of higher response rates and minimum recording errors.

Controlled release kinetics of p-aminosalicylic acid from biodegradable crosslinked polyesters for enhanced anti-mycobacterial activity

Unlike conventional polymeric drug delivery systems, where drugs are entrapped in polymers, this study focuses on the incorporation of the drug into the polymer backbone to achieve higher loading and sustained release. Crosslinked, biodegradable, xylitol based polyesters have been synthesized in this study. The bioactive drug moiety, p-aminosalicylic acid (PAS), was incorporated in xylitol based polyesters to impart its anti-mycobacterial activity. To understand the influence of the monomer chemistry on the incorporation of PAS and its subsequent release from the polymer, different diacids have been used. Controlled release profiles of the drug from these polyesters were studied under normal physiological conditions. The degradation of the polyesters varied from 48% to 76% and the release of PAS ranged from 54% to 65% of its initial loading in 7 days. A new model was developed to explain the release kinetics of PAS from the polymer that accounted for the polymer degradation and drug concentration. The thermal, mechanical, drug release and cytocompatibility properties of the polymers indicate their suitability in biomedical applications. The released products from these polymers were observed to be pharmacologically active against Mycobacteria. The high drug loading and sustained release also ensured enhanced efficacy. These polymers form biocompatible, biodegradable polyesters where the sustained release of PAS may be tailored for potential treatment of mycobacterial infections. Statement of significance In the present work, we report on novel polyesters with p-aminosalicylic acid (PAS) incorporated in the polymer backbone. The current work aims to achieve controlled release of PAS and ensures the delivered PAS is stable and pharmacologically active. The novelty of this work primarily involves the synthetic chemistry of polymerization and detailed analysis and efficacy of active PAS delivery. A new kinetic model has been developed to explain the PAS release profiles. These polymers are biodegradable, cytocompatible and anti-mycobacterial in nature. (C) 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

A Remarkably Efficient MnFe2O4-based Oxidase Nanozyme

Nanomaterials-based enzyme mimetics (nanozymes) have attracted considerable interest due to their applications in imaging, diagnostics, and therapeutic treatments. Particularly, metal-oxide nanozymes have been shown to mimic the interesting redox properties and biological activities of metalloenzymes. Here we describe an efficient synthesis of MnFe2O4 nanomaterials and show how the morphology can be controlled by using a simple co-precipitation method. The nanomaterials prepared by this method exhibit a remarkable oxidase-like activity. Interestingly, the activity is morphology-dependent, with nanooctahedra (NOh) exhibiting a catalytic efficiency of 2.21 x 10(9) M-1 s(-1), the highest activity ever reported for a nanozyme.