A novel structural derivative of natural alkaloid ellipticine, MDPSQ, induces necrosis in leukemic cells

DNA intercalating molecules are promising chemotherapeutic agents. In the present study, a novel DNA intercalating compound of pyrimido4',5':4,5]selenolo(2,3-b)quinoline series having 8-methyl-4-(3 diethylaminopropylamino) side chain is studied for its chemotherapeutic properties. Our results showed that 8-methyl-4-(3 diethylaminopropylamino) pyrimido 4',5':4,5] selenolo(2,3-b)quinoline (MDPSQ) induces cytotoxicity in a time- and concentration-dependent manner on leukemic cell lines. Both cell cycle analysis and tritiated thymidine assays revealed that MDPSQ affects DNA replication. Treatment with MDPSQ resulted in both elevated levels of DNA strand breaks and repair proteins, further indicating its cytotoxic effects. Besides, Annexin V/PI staining revealed that MDPSQ induces cell death by triggering necrosis rather than apoptosis.

A natural compound, methyl angolensate, induces mitochondrial pathway of apoptosis in Daudi cells

Natural products discovered from medicinal plants have played an important role in the treatment of cancer. In an effort to identify novel small molecules which can affect the proliferation of lymphoma cells, we tested methyl angolensate (MA), a plant derived tetranortriterpenoid, purified from the crude extract of the root callus of Soymida febrifuga commonly known as Indian red wood tree. We have tested MA for its cytotoxic properties on Burkitt's lymphoma cell lines, using various cellular assays. We observed that MA induces cytotoxicity in Daudi cells in a dose-dependent manner using trypan blue, MTT and LDH assays. We find that the treatment with MA led to activation of DNA double-strand break repair proteins including KU70 and KU80, suggesting the activation of nonhomologous DNA end joining pathway in surviving cells. Further, we find that methyl angolensate could induce apoptosis by cell cycle analysis, annexin V-FITC staining, DNA fragmentation and PARP cleavage. Besides, MA treatment led to reactive oxygen species generation and loss of mitochondrial transmembrane potential. These results suggest the activation of mitochondrial pathway of apoptosis. Hence, we identify MA as a potential chemotherapeutic agent against Daudi cells.

Effect of fluctuations on the freezing of a colloidal suspension in an external periodic potential

We incorporate the effects of fluctuations in a density functional analysis of the freezing of a colloidal liquid in the presence of an external potential generated by interfering laser beams. A mean-field treatment, using a density functional theory, predicts that with the increase in the strength of the modulating potential, the freezing transition changes from a first order to a continuous one via a tricritical point for a suitable choice of the modulating wavevectors. We demonstrate here that the continuous nature of the freezing transition at large values of the external potential V-e survives the presence of fluctuations. We also show that fluctuations tend to stabilize the liquid phase in the large V-e regime.

Angelica archengelica extract induced perturbation of rat skin and tight junctional protein (ZO-1) of HaCaT cells

Background and purpose of the study: Herbal enhancers compared to the synthetic ones have shown less toxis effects. Coumarins have been shown at concentrations inhibiting phospoliphase C-Y (Phc-Y) are able to enhance tight junction (TJ) permeability due to hyperpoalation of Zonolous Occludense-1 (ZO-1) proteins. The purpose of this study was to evaluate the influence of ethanolic extract of Angelica archengelica (AA-E) which contain coumarin on permeation of repaglinide across rat epidermis and on the tight junction plaque protein ZO-1 in HaCaT cells. Methods: Transepidermal water loss (TEWL) from the rat skin treated with different concentrations of AA-E was assessed by Tewameter. Scanning and Transmission Electron Microscopy (TEM) on were performed on AA-E treated rat skin portions. The possibility of AA-E influence on the architecture of tight junctions by adverse effect on the cytoplasmic ZO-1 in HaCaT cells was investigated. Finally, the systemic delivery of repaglinide from the optimized transdermal formulation was investigated in rats. Results: The permeation of repaglinide across excised rat epidermis was 7-fold higher in the presence of AA-E (5% w/v) as compared to propylene glycol:ethanol (7:3) mixture. The extract was found to perturb the lipid microconstituents in both excised and viable rat skin, although, the effect was less intense in the later. The enhanced permeation of repaglinide across rat epidermis excised after treatment with AA-E (5% w/v) for different periods was in concordance with the high TEWL values of similarly treated viable rat skin. Further, the observed increase in intercellular space, disordering of lipid structure and corneocyte detachment indicated considerable effect on the ultrastructure of rat epidermis. Treatment of HaCaT cell line with AA-E (0.16% w/v) for 6 hrs influenced ZO-1 as evidenced by reduced immunofluorescence of anti-TJP1 (ZO-1) antibody in Confocal Laser Scanning Microscopy studies (CLSM) studies. The plasma concentration of repaglinide from transdermal formulation was maintained higher and for longer time as compared to oral administration of repaglinide. Major conclusion: Results suggest the overwhelming influence of Angelica archengelica in enhancing the percutaneous permeation of repaglinide to be mediated through perturbation of skin lipids and tight junction protein (ZO-1).

Regulation of an 8-kDa peptide involved in testosterone production by luteinizing hormone in rat Leydig cells

Results of Western blot analysis carried out with an interstitial cell extract from male guinea pig and ovarian extract from immature female rats administered equine chorionic gonadotropin (eCG) provide supportive evidence to our earlier suggestion that an 8-kDa peptide is involved in acquisition of steroidogenic capacity by the rat Leydig cells. It was found that though the signal was observed in other tissues such as liver, kidney and lung which do not produce gonadal hormones, the peptide was modulated only by lutenizing hormone (LH) in the rat Leydig cells.

Zinc-substituted alpha-nickel hydroxide as an electrode material for alkaline secondary cells

Double hydroxides of the formula, Ni1-xZn2x (OH)(2) (CO3)(x). nH(2)O (x = 0.1 to 0.25) having the same structure as that of alpha-nickel hydroxide have been synthesized by partial substitution of zinc for nickel. The hydroxide having the composition x = 0.25 exhibits prolonged stability in 6 M KOH. Pasted electrodes comprising this material are rechargeable with a stabilized reversible discharge capacity of 410 +/- 15 mAh g(-1) of nickel even under suboptimal conditions of electrode fabrication. This compares favorably with the capacity values achieved for beta-nickel hydroxide (221 mAh g(-1)', This work; 297 mAh g(-1), Delahaye-Vidal and Figlarz;(1) 456 mAh g(-1), theoretical). (C) 1999 The Electrochemical Society. S0013-4651(98)01-071-4. All rights reserved.

Optimization of off-oriented Ge substrates for MOVPE-grown GaAs solar cells

GaAs/Ge heterostructures having abrupt interfaces were grown on 2degrees, 6degrees, and 9degrees off-cut Ge substrates and investigated by cross-sectional high-resolution transmission electron microscopy (HRTEM), scanning electron microscopy, photoluminescence spectroscopy and electrochemical capacitance voltage (ECV) profiler. The GaAs films were grown on off-oriented Ge substrates with growth temperature in the range of 600-700degreesC, growth rate of 3-12 mum/hr and a V/III ratio of 29-88. The lattice indexing of HRTEM exhibits an excellent lattice line matching between GaAs and Ge substrate. The PL spectra from GaAs layer on 6degrees off-cut Ge substrate shows the higher excitonic peak compared with 2degrees and 9degrees off-cut Ge substrates. In addition, the luminescence intensity from the GaAs solar cell grown on 6degrees off-cut is higher than on 9degrees off-cut Ge substrates and signifies the potential use of 6degrees off-cut Ge substrate in the GaAs solar cells industry. The ECV profiling shows an abrupt film/substrate interface as well as between various layers of the solar cell structures.

Remarkable photocytotoxicity in hypoxic HeLa cells by a dipyridophenazine copper(II) Schiff base thiolate

Copper(II) complexes Cu(satp)(L)] (1-3) of a Schiff base thiolate (salicylidene-2-aminothiophenol, H(2)satP) and phenanthroline bases (L), viz. 1,10-phenanthroline (phen in 1), dipyrido3,2-d:2',3'-f]quinoxaline (dpq in 2) and dipyrido3,2-a:2',3'-c]phenazine (dppz in 3), were prepared, characterized and their anaerobic DNA photocleavage activity and hypoxic photocytotoxicity studied. The redox active complexes show the Cu(II)-Cu(I) couple near -0.5 V for 1 and near 0.0 V vs. SCE (saturated calomel electrode) for 2 and 3. The one-electron paramagnetic complexes (similar to 1.85 mu(B)) are avid DNA binders giving K(b) values within 1.0 x 10(5) - 8.0 x 10(5) M(-1). Thermal melting and viscosity data along with molecular docking calculations suggest DNA groove and/or partial intercalative binding of the complexes. The complexes show anaerobic DNA cleavage activity in red light under argon via type-I pathway, while DNA photocleavage in air proceeds via hydroxyl radical pathway. The DFT (density functional theory) calculations reveal a thyil radical pathway for the anaerobic DNA photocleavage activity and suggest the possibility of generation of a transient copper(I) species due to bond breakage between the copper and sulfur to generate the thyil radical. An oxidation of the copper(I) species is likely by oxygen in an aerobic medium or by the buffer medium in an anaerobic condition. Complex 3 exhibits significant photocytotoxicity in HeLa cells (IC(50) = 8.3(+/- 1.0) mu M) in visible light, while showing lower dark toxicity (IC(50) = 17.2(+/- 1.0) mu M). A significant reduction in the dark toxicity is observed under hypoxic cellular conditions (IC(50) = 30.0(+/- 1.0) mu M in dark), while retaining its photocytotoxicity (IC(50) = 8.0(+/- 1.0) mu M). (C) 2011 Elsevier Inc. All rights reserved.

Calcium ruthenates: Determination of Gibbs energies of formation using electrochemical cells

Metallic Ru has been found to coexist separately with CaO, RuO2, and the interoxide phases, Ca2RuO4, Ca3Ru2O7, and CaRuO3, present along the pseudobinary system CaO-RuO2. The standard Gibbs energies of formation (Df((ox))G(o)) of the three calcium ruthenates from their component oxides have been measured in the temperature range 925-1350 K using solid-state cells with yttria-stabilized zirconia as the electrolyte and Ru+RuO2 as the reference electrode. The standard Gibbs energies of formation (Deltaf((ox))G(o)) of the compounds can be represented by Ca2RuO4:Deltaf((ox))G(o)/J mol(-1)=-38,340-6.611 T (+/-120), Ca3Ru2O7 : Df((ox))G(o)/J mol(-1)=-75,910-11.26 T (+/-180), and CaRuO3 : Deltaf((ox))G(o)/J mol(-1)=-35,480-3.844 T(+/-70). The data for Ca2RuO4 corresponds to the stoichiometric composition, which has an orthorhombic structure, space group Pbca, with short c axis ("S'' form). The structural features of the ternary oxides responsible for their mild entropy stabilization are discussed. A three-dimensional oxygen potential diagram for the system Ca-Ru-O is developed as a function of composition and temperature from the results obtained. Using the Neumann-Kopp rule to estimate the heat capacity of the ternary oxides relative to their constituent binary oxides, the standard enthalpies of formation of the three calcium ruthenates from the elements and their standard entropies at 298.15 K are evaluated. (C) 2003 The Electrochemical Society.

Particle dynamics in a turbulent particle–gas suspension at high Stokes number. Part 2. The fluctuating-force model

A fluctuating-force model is developed for representing the effect of the turbulent fluid velocity fluctuations on the particle phase in a turbulent gas–solid suspension in the limit of high Stokes number, where the particle relaxation time is large compared with the correlation time for the fluid velocity fluctuations. In the model, a fluctuating force is incorporated in the equation of motion for the particles, and the force distribution is assumed to be an anisotropic Gaussian white noise. It is shown that this is equivalent to incorporating a diffusion term in the Boltzmann equation for the particle velocity distribution functions. The variance of the force distribution, or equivalently the diffusion coefficient in the Boltzmann equation, is related to the time correlation functions for the fluid velocity fluctuations. The fluctuating-force model is applied to the specific case of a Couette flow of a turbulent particle–gas suspension, for which both the fluid and particle velocity distributions were evaluated using direct numerical simulations by Goswami & Kumaran (2010). It is found that the fluctuating-force simulation is able to quantitatively predict the concentration, mean velocity profiles and the mean square velocities, both at relatively low volume fractions, where the viscous relaxation time is small compared with the time between collisions, and at higher volume fractions, where the time between collisions is small compared with the viscous relaxation time. The simulations are also able to predict the velocity distributions in the centre of the Couette, even in cases in which the velocity distribution is very different from a Gaussian distribution.

Particle dynamics in a turbulent particle–gas suspension at high Stokes number. Part 1. Velocity and acceleration distributions

The effect of fluid velocity fluctuations on the dynamics of the particles in a turbulent gas–solid suspension is analysed in the low-Reynolds-number and high Stokes number limits, where the particle relaxation time is long compared with the correlation time for the fluid velocity fluctuations, and the drag force on the particles due to the fluid can be expressed by the modified Stokes law. The direct numerical simulation procedure is used for solving the Navier–Stokes equations for the fluid, the particles are modelled as hard spheres which undergo elastic collisions and a one-way coupling algorithm is used where the force exerted by the fluid on the particles is incorporated, but not the reverse force exerted by the particles on the fluid. The particle mean and root-mean-square (RMS) fluctuating velocities, as well as the probability distribution function for the particle velocity fluctuations and the distribution of acceleration of the particles in the central region of the Couette (where the velocity profile is linear and the RMS velocities are nearly constant), are examined. It is found that the distribution of particle velocities is very different from a Gaussian, especially in the spanwise and wall-normal directions. However, the distribution of the acceleration fluctuation on the particles is found to be close to a Gaussian, though the distribution is highly anisotropic and there is a correlation between the fluctuations in the flow and gradient directions. The non-Gaussian nature of the particle velocity fluctuations is found to be due to inter-particle collisions induced by the large particle velocity fluctuations in the flow direction. It is also found that the acceleration distribution on the particles is in very good agreement with the distribution that is calculated from the velocity fluctuations in the fluid, using the Stokes drag law, indicating that there is very little correlation between the fluid velocity fluctuations and the particle velocity fluctuations in the presence of one-way coupling. All of these results indicate that the effect of the turbulent fluid velocity fluctuations can be accurately represented by an anisotropic Gaussian white noise.

Haptic Feedback for Injecting Biological Cells using Miniature Compliant Mechanisms

We present a real-time haptics-aided injection technique for biological cells using miniature compliant mechanisms. Our system consists of a haptic robot operated by a human hand, an XYZ stage for micro-positioning, a camera for image capture, and a polydimethylsiloxane (PDMS) miniature compliant device that serves the dual purpose of an injecting tool and a force-sensor. In contrast to existing haptics-based micromanipulation techniques where an external force sensor is used, we use visually captured displacements of the compliant mechanism to compute the applied and reaction forces. The human hand can feel the magnified manipulation force through the haptic device in real-time while the motion of the human hand is replicated on the mechanism side. The images are captured using a camera at the rate of 30 frames per second for extracting the displacement data. This is used to compute the forces at the rate of 30 Hz. The force computed in this manner is sent at the rate of 1000 Hz to ensure stable haptic interaction. The haptic cell-manipulation system was tested by injecting into a zebrafish egg cell after validating the technique at a size larger than that of the cell.