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.

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.

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.

A hybrid finite element formulation for flexible multibody dynamics

This work deals with the transient analysis of flexible multibody systems within a hybrid finite element framework. Hybrid finite elements are based on a two-field variational formulation in which the displacements and stresses are interpolated separately yielding very good coarse mesh accuracy. Most of the literature on flexible multibody systems uses beam-theory-based formulations. In contrast, the use of hybrid finite elements uses continuum-based elements, thus avoiding the problems associated with rotational degrees of freedom. In particular, any given three-dimensional constitutive relations can be directly used within the framework of this formulation. Since the coarse mesh accuracy as compared to a conventional displacement-based formulation is very high, the scheme is cost effective as well. A general formulation is developed for the constrained motion of a given point on a line manifold, using a total Lagrangian method. The multipoint constraint equations are implemented using Lagrange multipliers. Various kinds of joints such as cylindrical, prismatic, and screw joints are implemented within this general framework. Hinge joints such as spherical, universal, and revolute joints are obtained simply by using shared nodes between the bodies. In addition to joints, the formulation and implementation details for a DC motor actuator and for prescribed relative rotation are also presented. Several example problems illustrate the efficacy of the developed formulation.

Spallation analysis with a closed trans-scale formulation damage evolution

A closed, trans-scale formulation of damage evolution based on the statistical microdamage mechanics is summarized in this paper. The dynamic function of damage bridges the mesoscopic and macroscopic evolution of damage. The spallation in an aluminium plate is studied with this formulation. It is found that the damage evolution is governed by several dimensionless parameters, i.e., imposed Deborah numbers De* and De, Mach number M and damage number S. In particular, the most critical mode of the macroscopic damage evolution, i.e., the damage localization, is deter-mined by Deborah number De+. Deborah number De* reflects the coupling and competition between the macroscopic loading and the microdamage growth. Therefore, our results reveal the multi-scale nature of spallation. In fact, the damage localization results from the nonlinearity of the microdamage growth. In addition, the dependence of the damage rate on imposed Deborah numbers De* and De, Mach number M and damage number S is discussed.

An elastoplastic constitutive relation of whisker-reinforced composite for meso damage: Part I - formulation

An elastoplastic constitutive relation is developed for meso damage of whisker-reinforced composites. A model is constructed that includes orientation distribution of whiskers and slip systems as well as interface and crystal sliding. Evolution of damage will be addressed. Given in Part I is the formulation while examples will be illustrated in Part II.

Statistical formulation and experimental determination of growth rate of micrometre cracks under impact loading

A new statistical formulation and a relevant experimental approach to determine the growth rate of microcracks were proposed. The method consists of experimental measurements and a statistical analysis' on the basis of the conservation law of number density of microcracks in phase space. As a practical example of the method, the growth rate of microcracks appearing in an aluminium alloy subjected to planar impact loading was determined to be ca. 10 mu m/mu s under a tensile stress of 1470 MPa and load duration between 0.26 mu s and 0.80 mu s.