Development of a bioanalytical method for the quantification of sinococuline in human plasma and its application in phase I clinical pharmacokinetic study

A selective, highly sensitive, precise, and novel bioanalytical method has been developed and validated to quantify sinococuline, an active constituent present in the phytopharmaceutical drug product containing Cocculus hirsutus plant extract, in vivo. Chromatographic separation was achieved on a Luna Omega Polar-C18 bonded analytical column maintained at 45°C. The isocratic mobile phase consisted of methanol and ammonium formate buffer (60:40, v/v) at acidic pH with a low flow rate of 0.250 mL/min. Detection was performed on an API 4000 mass spectrometer using electrospray ionization in positive polarity and multiple reaction monitoring mode to achieve a lower limit of quantification of 1.50 ng/mL. Excellent accuracy and precision were obtained after extracting the analyte from plasma samples using a chemical analogue as an internal standard in the absence of an isotope-labeled compound. The extraction efficacy was evidenced from recovery study, and the analyte was found to be stable in plasma. Validation study demonstrated linearity with coefficient of correlation, r ≥ 0.99, and minimal matrix effect. This bioanalytical method was successfully applied to evaluate pharmacokinetic parameters of sinococuline from a phase I clinical trial of an aqueous extract of C. hirsutus in healthy human volunteers.     

Dark and bright soliton solutions and computational modeling of nonlinear regularized long wave model

Nonlinear Dynamics - In this article, the authors simulate and study dark and bright soliton solutions of 1D and 2D regularized long wave (RLW) models. The RLW model occurred in various fields such...     

Synthesis,spectral investigation and development of tetrahedral copper(II) complexes as artificial metallonucleases and antimalarial agents

Seven new copper(II) complexes of type [Cu(A)(L)]?H₂O (A = sparfloxacin, ciprofloxacin, levofloxacin, gatifloxacin, pefloxacin, ofloxacin, norfloxacin; L = 5‐[(3‐chlorophenyl)diazenyl]‐4‐hydroxy‐1,3‐thiazole‐2(3H)‐thione) were synthesized and characterized using elemental and thermogravimetric analyses, and electronic, electron paramagnetic resonance (EPR), Fourier transform infrared and liquid chromatography–mass spectroscopies. Tetrahedral geometry around copper is assigned in all complexes using EPR and electronic spectral analyses. All complexes were investigated for their interaction with herring sperm DNA utilizing absorption titration (K_b = 1.27–3.13 × 10⁵ M^?1) and hydrodynamic volume measurement studies. The studies suggest the classical intercalative mode of DNA binding. The cleavage reaction on pUC19 DNA was monitored by agarose gel electrophoresis. The results indicate that the Cu(II) complexes can more effectively promote the cleavage of plasmid DNA. The superoxide dismutase mimic activity of the complexes was evaluated by nitroblue tetrazolium assay, and the complexes catalysed the dismutation of superoxide at pH = 7.8 with IC₅₀ values in the range 0.597–0.900 μM. The complexes were screened for their in vitro antibacterial activity against five pathogenic bacteria. All the complexes are good cytotoxic agents and show LC₅₀ values ranging from 5.559 to 11.912 µg ml^?1. All newly synthesized Cu(II) complexes were also evaluated for their in vitro antimalarial activity against Plasmodium falciparum strain (IC₅₀ = 0.62–2.0 µg ml^?1). Copyright © 2015 John Wiley & Sons, Ltd.     

Degree-regular triangulations of torus and Klein bottle

A triangulation of a connected closed surface is called weakly regular if the action of its automorphism group on its vertices is transitive. A triangulation of a connected closed surface is called degree-regular if each of its vertices have the same degree. Clearly, a weakly regular triangulation is degree-regular. In [8], Lutz has classified all the weakly regular triangulations on at most 15 vertices. In [5], Datta and Nilakantan have classified all the degree-regular triangulations of closed surfaces on at most 11 vertices. In this article, we have proved that any degree-regular triangulation of the torus is weakly regular. We have shown that there exists ann-vertex degree-regular triangulation of the Klein bottle if and only if n is a composite number ≥ 9. We have constructed two distinctn-vertex weakly regular triangulations of the torus for eachn ≥ 12 and a (4m + 2)-vertex weakly regular triangulation of the Klein bottle for eachm ≥ 2. For 12 ≤n ≤ 15, we have classified all then-vertex degree-regular triangulations of the torus and the Klein bottle. There are exactly 19 such triangulations, 12 of which are triangulations of the torus and remaining 7 are triangulations of the Klein bottle. Among the last 7, only one is weakly regular.     

Critical Behavior of Two Interacting Linear Polymer Chains in a Good Solvent

A model of two interacting (chemically different) linear polymer chains is solved exactly using the real-space renormalization group transformation on a family of Sierpinski gasket type fractals and on a truncated 4-simplex lattice. The members of the family of the Sierpinski gasket-type fractals are characterized by an integer scale factorb which runs from 2 to ∞. The Hausdorff dimensiond _F of these fractals tends to 2 from below asb → ∞. We calculate the contact exponenty for the transition from the State of segregation to a State in which the two chains are entangled forb = 2-5. Using arguments based on the finite-size scaling theory, we show that forb→∞, y = 2 - v(b) d _F, wherev is the end-toend distance exponent of a chain. For a truncated 4-simplex lattice it is shown that the system of two chains either remains in a State in which these chains are intermingled in such a way that they cannot be told apart, in the sense that the chemical difference between the polymer chains completely drop out of the thermodynamics of the system, or in a State in which they are either zipped or entangled. We show the region of existence of these different phases separated by tricritical lines. The value of the contact exponenty is calculated at the tricritical points.     

Dielectric properties of KDP-type ferroelectric crystals in the presence of external electric field

Considering external electric field as well as third- and fourth-order phonon anharmonic interaction terms in the pseudospin-lattice coupled mode (PLCM) model Hamiltonian for KDP-type ferroelectrics, expressions for field-dependent shift, width, renormalized soft mode frequency, Curie temperature, dielectric constant and dielectric loss are evaluated. For the calculation, method of statistical double-time temperature-dependent Green’s function has been used. By fitting model values of physical quantities, temperature and electric field dependences of soft mode frequency, dielectric constant and loss have been calculated which compare well with experimental results of Baumgartner [8] and Choi and Lockwood [9]. Both dielectric constant and loss decrease with electric field.     

Enzymes immobilized on montmorillonite: comparison of performance in batch and packed-bed reactors

Summary The enzymes a-amylase, invertase and glucoamylase were immobilized on acid activated montmorillonite using two techniques, viz. adsorption and covalent binding, and their activities were tested in a batch and packed-bed reactor and were compared. The packed-bed reactor showed an improved performance for all immobilized enzymes, which was attributed to lowering of diffusional restrictions to mass transfer. Lower activity in case of batch reactor for immobilized invertase was due to a combined effect of loss of native conformation of enzyme on account of immobilization and mass transfer resistances due to improper diffusion of substrate to the active site of enzyme. For immobilized glucoamylase, the packed-bed reactor demonstrated exceptionally high activity that was very close to the free enzyme. Covalently bound glucoamylase showed higher activity than the free enzyme.     

An efficient two-step synthesis of 3-allylindoles

A two-step synthetic sequence for an efficient synthesis of 3-allylindoles is described.     

Feedback stabilization of snap-through buckling in a preloaded two-bar linkage with hysteresis

We study a linearly damped preloaded two-bar linkage that exhibits hysteresis due to the presence of multiple attracting equilibria. The dynamics at the unstable equilibrium, through which a snap-through buckle occurs, are not linearizable due to a solution-dependent singularity. We stabilize the unstable equilibrium using two distinct non-linear controllers. The feedback-linearization controller requires knowledge of the linkage parameters, whereas the robust version of the intrinsic non-linear proportional-derivative controller requires only an upper bound on the stiffness.     

Pollution-error in the h-version of the finite-element method and the local quality of a-posteriori error estimators

In this paper we study the pollution-error in the h-version of the finite element method and its effect on the local quality of a-posteriori error estimators. We show that the pollution-effect in an interior subdomain depends on the relationship between the mesh inside and outside the subdomain and the smoothness of the exact solution. We also demonstrate that it is possible to guarantee the quality of local error estimators in any mesh-patch in the interior of a finite-element mesh by employing meshes which are sufficiently refined outside the patch.