Automatic finite element formulation and assembly of hyperelastic higher order structural models

The formulation of higher order structural models and their discretization using the finite element method is difficult owing to their complexity, especially in the presence of non-linearities. In this work a new algorithm for automating the formulation and assembly of hyperelastic higher-order structural finite elements is developed. A hierarchic series of kinematic models is proposed for modeling structures with special geometries and the algorithm is formulated to automate the study of this class of higher order structural models. The algorithm developed in this work sidesteps the need for an explicit derivation of the governing equations for the individual kinematic modes. Using a novel procedure involving a nodal degree-of-freedom based automatic assembly algorithm, automatic differentiation and higher dimensional quadrature, the relevant finite element matrices are directly computed from the variational statement of elasticity and the higher order kinematic model. Another significant feature of the proposed algorithm is that natural boundary conditions are implicitly handled for arbitrary higher order kinematic models. The validity algorithm is illustrated with examples involving linear elasticity and hyperelasticity. (C) 2013 Elsevier Inc. All rights reserved.

Dual enzyme responsive and targeted nanocapsules for intracellular delivery of anticancer agents

We report the fabrication of dual enzyme responsive hollow nanocapsules which can be targeted to deliver anticancer agents specifically inside cancer cells. The enzyme responsive elements, integrated in the nanocapsule walls, undergo degradation in the presence of either trypsin or hyaluronidase leading to the release of encapsulated drug molecules. These nanocapsules, which were crosslinked and functionalised with folic acid, showed minimal drug leakage when kept in pH 7.4 PBS buffer, but released the drug molecules at a rapid rate in the presence of either one of the triggering enzymes. Studies on cellular interactions of these nanocapsules revealed that doxorubicin loaded nanocapsules were taken up by cervical cancer cells via folic acid receptor medicated endocytosis. Interestingly the nanocapsules were able to disintegrate inside the cancer cells and release doxorubicin which then migrated into the nucleus to induce cell death. This study indicates that these nanocapsules fabricated from biopolymers can serve as an excellent platform for targeted intracellular drug delivery to cancer cells.

Formulation of nanotized curcumin and demonstration of its antimalarial efficacy

Aim: The present study was conducted to overcome the disadvantages associated with the poor water solubility and low bioavailability of curcumin by synthesizing nanotized curcumin and demonstrating its efficacy in treating malaria. Materials and methods: Nanotized curcumin was prepared by a modified emulsion-diffusion-evaporation method and was characterized by means of transmission electron microscopy, atomic force microscopy, dynamic light scattering, Zetasizer, Fourier transform infrared spectroscopy, and differential thermal analysis. The novelty of the prepared nanoformulation lies in the fact that it was devoid of any polymeric matrices used in conventional carriers. The antimalarial efficacy of the prepared nanotized curcumin was then checked both in vitro and in vivo. Results: The nanopreparation was found to be non-toxic and had a particle size distribution of 20-50 nm along with improved aqueous dispersibility and an entrapment efficiency of 45%. Nanotized curcumin (half maximal inhibitory concentration IC50]: 0.5 mu M) was also found to be ten-fold more effective for growth inhibition of Plasmodium falciparum in vitro as compared to its native counterpart (IC50: 5 mu M). Oral bioavailability of nanotized curcumin was found to be superior to that of its native counterpart. Moreover, when Plasmodium berghei-infected mice were orally treated with nanotized curcumin, it prolonged their survival by more than 2 months with complete clearance of parasites in comparison to the untreated animals, which survived for 8 days only. Conclusion: Nanotized curcumin holds a considerable promise in therapeutics as demonstrated here for treating malaria as a test system.

Development, in vitro and in vivo characterization of zoledronic acid functionalized hydroxyapatite nanoparticle based formulation for treatment of osteoporosis in animal model

We investigated the potential of using novel zoledronic acid (ZOL)-hydroxyapatite (HA) nanoparticle based drug formulation in a rat model of postmenopausal osteoporosis. By a classical adsorption method, nanoparticles of HA loaded with ZOL (HNLZ) drug formulation with a size range of 100-130 nm were prepared. 56 female Wistar rats were ovariectomized (OVX) or sham-operated at 3 months of age. Twelve weeks post surgery, rats were randomized into seven groups and treated with various doses of HNLZ (100, 50 and 25 mu g/kg, intravenous single dose), ZOL (100 mu g/kg, intravenous single dose) and HA nanoparticle (100 mu g/kg, intravenous single dose). Untreated OVX and sham OVX served as controls. After three months treatment period, we evaluated the mechanical properties of the lumbar vertebra and femoral mid-shaft. Femurs were also tested for trabecular microarchitecture. Sensitive biochemical markers of bone formation and bone resorption in serum were also determined. With respect to improvement in the mechanical strength of the lumbar spine and the femoral mid-shaft, the therapy with HNLZ drug formulation was more effective than ZOL therapy in OVX rats. Moreover, HNLZ drug therapy preserved the trabecular microarchitecture better than ZOL therapy in OVX rats. Furthermore, the HNLZ drug formulation corrected increase in serum levels of bone-specific alkaline phosphatase, procollagen type I N-terminal propeptide, osteocalcin, tartrate-resistant acid phosphatase 5b and C-telopeptide of type 1 collagen better than ZOL therapy in OVX rats. The results strongly suggest that HNLZ novel drug formulation appears to be more effective approach for treating severe osteoporosis in humans. (C) 2014 Elsevier B.V. All rights reserved.

Effect of metal oxidation state on FRET: a Cu(I) silent but selectively Cu(II) responsive fluorescent reporter and its bioimaging applications

Copper(II) and copper(I) complexes of a newly designed and crystallographically characterized Schiff base (HL) derived from rhodamine hydrazide and cinnamaldehyde were isolated in pure form formulated as Cu(L)(NO3)] (L-Cu) (1) and Cu(HL)(CH3CN)(H2O)]ClO4 (HL-Cu) (2), and characterized by physicochemical and spectroscopic tools. Interestingly, complex 1 but not 2 offers red fluorescence in solution state, and eventually HL behaves as a Cu(II) ions selective FRET based fluorosensor in HEPES buffer (1 mM, acetonitrile-water: 1/5, v/v) at 25 degrees C at biological pH with almost no interference of other competitive ions. The dependency of the FRET process on the +2 oxidation state of copper has been nicely supported by exhaustive experimental studies comprising electronic, fluorimetric, NMR titration, and theoretical calculations. The sensing ability of HL has been evaluated by the LOD value towards Cu(II) ions (83.7 nM) and short responsive time (5-10 s). Even the discrimination of copper(I) and copper(II) has also been done using only UV-Vis spectroscopic study. The efficacy of this bio-friendly probe has been determined by employing HL to detect the intercellular distribution of Cu(II) ions in HeLa cells by developing image under fluorescence microscope.

Remotely triggered micro-shock wave responsive drug delivery system for resolving diabetic wound infection and controlling blood sugar levels

A novel, micro-shock wave responsive spermidine and dextran sulfate microparticle was developed. Almost 90% of the drug release was observed when the particles were exposed to micro-shock waves 5 times. Micro-shock waves served two purposes; of releasing the antibiotic from the system and perhaps disrupting the S. aureus biofilm in the skin infection model. A combination of shock waves with ciprofloxacin loaded microparticles could completely cure the S. aureus infection lesion in a diabetic mouse model. As a proof of concept insulin release was triggered using micro-shock waves in diabetic mice to reduce the blood glucose level. Insulin release could be triggered for at least 3 days by exposing subcutaneously injected insulin loaded particles.

Charge Transfer Induces Formation of Stimuli-Responsive, Chiral, Cohesive Vesicles-on-a-String that Eventually Turn into a Hydrogel

A charge transfer (CT) mediated two-component, multistimuli responsive supergelation involving a L-histidine-appended pyrenyl derivative (PyHisOMe) as a donor and an asymmetric bolaamphiphilic naphthalene-diimide (Asym-NDI) derivative as an acceptor in a 2: 1 mixture of H2O/MeOH was investigated. Asym-NDI alone self-assembled into pH-responsive vesicular nanostructures in water. Excellent selectivity in CT gel formation was achieved in terms of choosing amino acid appended pyrenyl donor scaffolds. Circular di-chroism and morphological studies suggested formation of chiral, interconnected vesicular assemblies resembling ``pearls-on-a-string'' from these CT mixed stacks. XRD studies revealed the formation of monolayer lipid membranes from these CT mixed stacks that eventually led to the formation of individual vesicles. Strong cohesive forces among the interconnected vesicles originate from the protrusion of the oxyethylene chains from the surfaces of the chiral vesicles.

Mesoporous silica-chondroitin sulphate hybrid nanoparticles for targeted and bio-responsive drug delivery

This work proposes the fabrication of a novel targeted drug delivery system based on mesoporous silica-biopolymer hybrids that can release drugs in response to biological stimuli present in cancer cells. The proposed system utilizes mesoporous silica nanoparticles as a carrier to host the drug molecules. A bio-polymer cap is attached onto these particles which serves the multiple functions of drug retention, targeting and bio-responsive drug release. The biopolymer chondroitin sulphate used here is a glycosaminoglycan that can specifically bind to receptors over-expressed in cancer cells. This molecule also possesses the property of disintegrating upon exposure to enzymes over-expressed in cancer cells. When these particles interact with cancer cells, the chondroitin sulphate present on the surface recognizes and attaches onto the CD44 receptors facilitating the uptake of these particles. The phagocytised particles are then exposed to the degradative enzymes, such as hyaluronidase present inside the cancer cells, which degrade the cap resulting in drug release. By utilizing a cervical cancer cell line we have demonstrated the targetability and intracellular delivery of hydrophobic drugs encapsulated in these particles. It was observed that the system was capable of enhancing the anticancer activity of the hydrophobic drug curcumin. Overall, we believe that this system might prove to be a valuable candidate for targeted and bioresponsive drug delivery.

Water-responsive carbon nanotubes for selective detection of toxic gases

Ammonia plays an important role in our daily lives and hence its quantitative and qualitative sensing has become necessary. Bulk structure of carbon nanotubes (CNTs) has been employed to detect the gas concentration of 10 ppm. Hydrophobic CNTs were turned to hydrophilic via the application of a ramp electric field that allowed confinement of a controlled amount of water inside CNT microstructure. These samples were then also used to detect different gases. A comparative study has been performed for sensing three reducing gases, namely, ammonia, sulphur-di-oxide, and hydrogen sulphide to elaborate the selectivity of the sensor. A considerable structural bending in the bulk CNT was observed on evaporation of the confined water, which can be accounted to the zipping of individual nanotubes. However, the rate of the stress induced on these bulk microstructures increased on the exposure of ammonia due to the change in the surface tension of the confined solvent. A prototype of an alarm system has been developed to illustrate sensing concept, wherein the generated stress in the bulk CNT induces a reversible loss in electrical contact that changes the equivalent resistance of the electrical circuit upon exposure to the gas. (C) 2015 AIP Publishing LLC.

Efficacious redox-responsive gene delivery in serum by ferrocenylated monomeric and dimeric cationic cholesterols

Herein, we present the design and synthesis of new redox-active monomeric and dimeric (gemini) cationic lipids based on ferrocenylated cholesterol derivatives for gene delivery. The cationic cholesterols are shown to be transfection efficient after being formulated with the neutral helper lipid DOPE in the presence of serum (FBS). The redox activity of the resulting co-liposomes and their lipoplexes could be regulated using the alkanyl ferrocene moiety attached to the ammonium head groups of the cationic cholesterols. Atomic force microscopy (AFM), dynamic light scattering (DLS) and zeta potential measurements were performed to characterize the co-liposomal aggregates and their complexes with pDNA. The transfection efficiency of lipoplexes could be tuned by changing the oxidation state of the ferrocene moiety. The gene transfection capability was assayed in terms of green fluorescence protein (GFP) expression using pEGFP-C3 plasmid DNA in three cell lines of different origins, namely Caco-2, HEK293T and HeLa, in the presence of serum. The vesicles possessing ferrocene in the reduced state induced an efficient transfection, even better than a commercial reagent Lipofectamine 2000 (Lipo 2000) as evidenced by flow cytometry and fluorescence microscopy. All the co-liposomes containing the oxidized ferrocene displayed diminished levels of gene expression. Gene transfection events from the oxidized co-liposomes were further potentiated by introducing ascorbic acid (AA) as a reducing agent during lipoplex incubation with cells, leading to the resumption of transfection activity. Assessment of transfection capability of both reduced and oxidized co-liposomes was also undertaken following cellular internalization of labelled pDNA using confocal microscopy and flow cytometry. Overall, we demonstrate here controlled gene transfection activities using redox-driven, transfection efficient cationic monomeric and dimeric cholesterol lipids. Such systems could be used in gene delivery applications where transfection needs to be performed spatially or temporally.

GRMHD formulation of highly super-Chandrasekhar magnetized white dwarfs: stable configurations of non-spherical white dwarfs

The topic of magnetized super-Chandrasekhar white dwarfs is in the limelight, particularly in the last few years, since our proposal of their existence. By full-scale general relativistic magnetohydrodynamic (GRMHD) numerical analysis, we confirm in this work the existence of stable, highly magnetized, significantly super-Chandrasekhar white dwarfs with mass more than 3 solar mass. While a poloidal field geometry renders the white dwarfs oblate, a toroidal field makes them prolate retaining an overall quasi-spherical shape, as speculated in our earlier work. These white dwarfs are expected to serve as the progenitors of over-luminous type Ia supernovae.

Alternative Formulation of the Discrete Linear Quadratic Regulator (DLQR)

In this paper, an alternative apriori and aposteriori formulation has been derived for the discrete linear quadratic regulator (DLQR) in a manner analogous to that used in the discrete Kalman filter. It has been shown that the formulation seamlessly fits into the available formulation of the DLQR and the equivalent terms in the existing formulation and the proposed formulation have been identified. Thereafter, the significance of this alternative formulation has been interpreted in terms of the sensitivity of the controller performances to any changes in the states or to changes in the control inputs. The implications of this alternative formulation to adaptive controller tuning have also been discussed.

Influence of fuel hydrogen fraction on syngas fueled SI engine: Fuel thermo-physical property analysis and in-cylinder experimental investigations

Hydrogen, either in pure form or as a gaseous fuel mixture specie enhances the fuel conversion efficiency and reduce emissions in an internal combustion engine. This is due to the reduction in combustion duration attributed to higher laminar flame speeds. Hydrogen is also expected to increase the engine convective heat flux, attributed (directly or indirectly) to parameters like higher adiabatic flame temperature, laminar flame speed, thermal conductivity and diffusivity and lower flame quenching distance. These factors (adversely) affect the thermo-kinematic response and offset some of the benefits. The current work addresses the influence of mixture hydrogen fraction in syngas on the engine energy balance and the thermo-kinematic response for close to stoichiometric operating conditions. Four different bio-derived syngas compositions with fuel calorific value varying from 3.14 MJ/kg to 7.55 MJ/kg and air fuel mixture hydrogen fraction varying from 7.1% to 14.2% by volume are used. The analysis comprises of (a) use of chemical kinetics simulation package CHEMKIN for quantifying the thermo-physical properties (b) 0-D model for engine in-cylinder analysis and (c) in-cylinder investigations on a two-cylinder engine in open loop cooling mode for quantifying the thermo-kinematic response and engine energy balance. With lower adiabatic flame temperature for Syngas, the in-cylinder heat transfer analysis suggests that temperature has little effect in terms of increasing the heat flux. For typical engine like conditions (700 K and 25 bar at CR of 10), the laminar flame speed for syngas exceeds that of methane (55.5 cm/s) beyond mixture hydrogen fraction of 11% and is attributed to the increase in H based radicals. This leads to a reduction in the effective Lewis number and laminar flame thickness, potentially inducing flame instability and cellularity. Use of a thermodynamic model to assess the isolated influence of thermal conductivity and diffusivity on heat flux suggests an increase in the peak heat flux between 2% and 15% for the lowest (0.420 MW/m(2)) and highest (0.480 MW/m(2)) hydrogen containing syngas over methane (0.415 MW/m(2)) fueled operation. Experimental investigations indicate the engine cooling load for syngas fueled engine is higher by about 7% and 12% as compared to methane fueled operation; the losses are seen to increase with increasing mixture hydrogen fraction. Increase in the gas to electricity efficiency is observed from 18% to 24% as the mixture hydrogen fraction increases from 7.1% to 9.5%. Further increase in mixture hydrogen fraction to 14.2% results in the reduction of efficiency to 23%; argued due to the changes in the initial and terminal stages of combustion. On doubling of mixture hydrogen fraction, the flame kernel development and fast burn phase duration decrease by about 7% and 10% respectively and the terminal combustion duration, corresponding to 90%-98% mass burn, increases by about 23%. This increase in combustion duration arises from the cooling of the near wall mixture in the boundary layer attributed to the presence of hydrogen. The enhancement in engine cooling load and subsequent reduction in the brake thermal efficiency with increasing hydrogen fraction is evident from the engine energy balance along with the cumulative heat release profiles. Copyright (C) 2015, Hydrogen Energy Publications, LLC. Published by Elsevier Ltd. All rights reserved.

Lower-Bound Axisymmetric Formulation for Geomechanics Problems Using Nonlinear Optimization

A lower-bound limit analysis formulation, by using two-dimensional finite elements, the three-dimensional Mohr-Coulomb yield criterion, and nonlinear optimization, has been given to deal with an axisymmetric geomechanics stability problem. The optimization was performed using an interior point method based on the logarithmic barrier function. The yield surface was smoothened (1) by removing the tip singularity at the apex of the pyramid in the meridian plane and (2) by eliminating the stress discontinuities at the corners of the yield hexagon in the pi-plane. The circumferential stress (sigma(theta)) need not be assumed. With the proposed methodology, for a circular footing, the bearing-capacity factors N-c, N-q, and N-gamma for different values of phi have been computed. For phi = 0, the variation of N-c with changes in the factor m, which accounts for a linear increase of cohesion with depth, has been evaluated. Failure patterns for a few cases have also been drawn. The results from the formulation provide a good match with the solutions available from the literature. (C) 2014 American Society of Civil Engineers.

GRMHD formulation of highly super-Chandrasekhar rotating magnetized white dwarfs: stable configurations of non-spherical white dwarfs

Here we extend the exploration of significantly super-Chandrasekhar magnetized white dwarfs by numerically computing axisymmetric stationary equilibria of differentially rotating magnetized polytropic compact stars in general relativity (GR), within the ideal magnetohydrodynamic regime. We use a general relativistic magnetohydrodynamic (GRMHD) framework that describes rotating and magnetized axisymmetric white dwarfs, choosing appropriate rotation laws and magnetic field profiles (toroidal and poloidal). The numerical procedure for finding solutions in this framework uses the 3 + 1 formalism of numerical relativity, implemented in the open source XNS code. We construct equilibrium sequences by varying different physical quantities in turn, and highlight the plausible existence of super-Chandrasekhar white dwarfs, with masses in the range of 2-3 solar mass, with central (deep interior) magnetic fields of the order of 10(14) G and differential rotation with surface time periods of about 1-10 s. We note that such white dwarfs are candidates for the progenitors of peculiar, overluminous Type Ia supernovae, to which observational evidence ascribes mass in the range 2.1-2.8 solar mass. We also present some interesting results related to the structure of such white dwarfs, especially the existence of polar hollows in special cases.