Development and validation of an LC-ESI-MS/MS method for simultaneous quantitation of olmesartan and pioglitazone in rat plasma and its pharmacokinetic application

A simple, high‐throughput and specific high‐performance liquid chromatography tandem mass spectrometry method has been developed and validated according to the FDA guidelines for simultaneous quantification of olmesartan and pioglitazone in rat plasma. The bioanalytical method consists of liquid–liquid extraction and quantitation by triple quadrupole mass spectrometry using electrospray ionization technique, operating in multiple reaction monitoring and positive ion modes. The compounds were eluted isocratically on a C₁₈ column with a mobile phase consisting of a mixture of methanol and water (containing 0.5% formic acid) in a ratio of 9:1. The response to olmesartan and pioglitazone was linear over the range 0.01–10 µg/mL. The validation results demonstrated that the method had satisfactory precision and accuracy across the calibration range. Intra‐ and inter‐day precisions ranged from 0.66 to 3.32 and from 0.94 to 2.93% (%CV), respectively. The accuracy determined at three quality control levels was within 91.27–107.28%. There was no evidence of instability of the analytes in rat plasma following the stability studies. The method proved highly reproducible and sensitive and was successfully applied in a pharmacokinetic study after single dose oral administration of olmesartan and pioglitazone to the rat. Copyright © 2010 John Wiley & Sons, Ltd.     

Bilirubin protects grafts against nonspecific inflammation-induced injury in syngeneic intraportal islet transplantation

Nonspecific inflammatory response is the major cause for failure of islet grafts at the early phase of intraportal islet transplantation (IPIT). Bilirubin, a natural product of heme catabolism, has displayed anti-oxidative and anti-inflammatory activities. The present study has demonstrated that bilirubin protected islet grafts by inhibiting nonspecific inflammatory response in a syngeneic rat model of IPIT. The inflammation-induced cell injury was mimicked by exposing cultured rat insulinoma INS-1 cells to cytokines (IL-1β, TNF-α and IFN-γ) in in vitro assays. At appropriate lower concentrations, bilirubin significantly attenuated the reduced cell viability and enhanced cell apoptosis induced by cytokines, and protected the insulin secretory function of INS-1 cells. Diabetic inbred male Lewis rats induced by streptozotocin underwent IPIT at different islet equivalents (IEQs) (optimal dose of 1000, and suboptimal doses of 750 or 500), and bilirubin was administered to the recipients every 12 h, starting from one day before transplantation until 5 days after transplantation. Administration of bilirubin improved glucose control and enhanced glucose tolerance in diabetic recipients, and reduced the serum levels of inflammatory mediators including IL-1β, TNF-α, soluble intercellular adhesion molecule 1, monocyte chemoattractant protein-1 and NO, and inhibited the infiltration of Kupffer cells into the islet grafts, and restored insulin-producing ability of transplanted islets.     

Loss reduction in silicon nanophotonic waveguide micro-bends through etch profile improvement

Single mode silicon photonic wire waveguides allow low-loss sharp micro-bends, which enables compact photonic devices and circuits. The circuit compactness is achieved at the cost of loss induced by micro-bends, which can seriously affect the device performance. The bend loss strongly depends on the bend radius, polarization, waveguide dimension and profile. In this paper, we present the effect of waveguide profile on the bend loss. We present waveguide profile improvement with optimized etch chemistry and the role of etch chemistry in adapting the etch profile of silicon is investigated. We experimentally demonstrate that by making the waveguide sidewalls vertical, the bend loss can be reduced up to 25% without affecting the propagation loss of the photonic wires. The bend loss of a 2 μm bend has been reduced from 0.039dB/90° bend to 0.028dB/90° bend by changing the sidewall angle from 81° to 90°, respectively. The propagation loss of 2.7 ± 0.1dB/cm and 3 ± 0.09dB/cm was observed for sloped and vertical photonic wires respectively was obtained.     

The augmented multiplicative coalescent,bounded size rules and critical dynamics of random graphs

Random graph models with limited choice have been studied extensively with the goal of understanding the mechanism of the emergence of the giant component. One of the standard models are the Achlioptas random graph processes on a fixed set of \(n\) vertices. Here at each step, one chooses two edges uniformly at random and then decides which one to add to the existing configuration according to some criterion. An important class of such rules are the bounded-size rules where for a fixed \(K\ge 1\) , all components of size greater than \(K\) are treated equally. While a great deal of work has gone into analyzing the subcritical and supercritical regimes, the nature of the critical scaling window, the size and complexity (deviation from trees) of the components in the critical regime and nature of the merging dynamics has not been well understood. In this work we study such questions for general bounded-size rules. Our first main contribution is the construction of an extension of Aldous’s standard multiplicative coalescent process which describes the asymptotic evolution of the vector of sizes and surplus of all components. We show that this process, referred to as the standard augmented multiplicative coalescent (AMC) is ‘nearly’ Feller with a suitable topology on the state space. Our second main result proves the convergence of suitably scaled component size and surplus vector, for any bounded-size rule, to the standard AMC. This result is new even for the classical Erd?s–Rényi setting. The key ingredients here are a precise analysis of the asymptotic behavior of various susceptibility functions near criticality and certain bounds from Bhamidi et al. (The barely subcritical regime. Arxiv preprint, 2012) on the size of the largest component in the barely subcritical regime.     

Formation constants of binary chelates of Cu(II)/Ni(II) with 4-chloro and 4-amino picolinic acid N-oxide in aquo organic media

The proton ligand constants of 4-chloro and 4-amino picolinic acid N-oxide and the formation constants of corresponding binary chelates of Cu(II) and Ni(II) have been measured at 30°C and 0.1M ionic strength in varying percentages of dioxane-water, acetone-water, ethanol-water and isopropanol-water. The results are discussed with reference to the change in dielectric constants of water in the presence of organic solvent, change in the structuredness of water, change in hydrogen bonding ability of the organic solvent in water, solvent basicity and proton solvation by organic solvent. The values have been compared with aqueous and mixed aqueous systems of picolinic acid N-oxide and 4-methoxy picolinic acid N-oxide.     

Axial eigenfunctions and inhomogeneous solutions for the three-dimensional Stokes system with an application to natural convection in a cylinder

This paper presents two contributions to the analysis of three-dimensional slow viscous flows in cylinders of circular section. First the vector axial eigenfunctions for this geometry, namely those that satisfy homogeneous boundary conditions on the flat end walls, are derived. Secondly a method is presented to find particular solutions to the inhomogeneous Stokes equations in this geometry. These new results, together with some results obtained earlier, are used to analyse slow natural convection in a vertical cylinder completely filled with a viscous liquid. The fluid motion is generated by the differential heating of the walls of the cylinder. The natural convection flow field is shown to be a superposition of an inhomogeneous field, the fields generated by the vector eigenfunctions and a Stokes flow field. A by-product of this work has been the identification of constraints on the boundary data that have to be satisfied in order for the eigenfunction expansions to work; this knowledge will be useful when attempts are made to prove the completeness of these Stokes flow eigenfunctions.     

Exact results for spin dynamics and fractionalization in the Kitaev Model

We present certain exact analytical results for dynamical spin correlation functions in the Kitaev Model. It is the first result of its kind in nontrivial quantum spin models. The result is also novel: in spite of the presence of gapless propagating Majorana fermion excitations, dynamical two spin correlation functions are identically zero beyond nearest neighbor separation. This shows existence of a gapless but short range spin liquid. An unusual, all energy scale fractionalization of a spin-flip quanta, into two infinitely massive pi fluxes and a dynamical Majorana fermion, is shown to occur. As the Kitaev Model exemplifies topological quantum computation, our result presents new insights into qubit dynamics and generation of topological excitations.     

Integrating NiCo Alloys with Their Oxides as Efficient Bifunctional Cathode Catalysts for Rechargeable Zinc–Air Batteries

The lack of high‐efficient, low‐cost, and durable bifunctional electrocatalysts that act simultaneously for the oxygen reduction reaction (ORR) and the oxygen evolution reaction (OER) is currently one of the major obstacles to commercializing the electrical rechargeability of zinc–air batteries. A nanocomposite CoO‐NiO‐NiCo bifunctional electrocatalyst supported by nitrogen‐doped multiwall carbon nanotubes (NCNT/CoO‐NiO‐NiCo) exhibits excellent activity and stability for the ORR/OER in alkaline media. More importantly, real air cathodes made from the bifunctional NCNT/CoO‐NiO‐NiCo catalysts further demonstrated superior performance to state‐of‐the‐art Pt/C or Pt/C+IrO₂ catalysts in primary and rechargeable zinc–air batteries.