Rapid UPLC - MS/MS method for the determination of ketoprofen in human dermal microdialysis samples

Dermal microdialysis (DMD) is a technique capable of determining the percutaneous penetration of drugs from topical formulations intended for local and/or regional activity. Typically, the concentrations of drug collected in dialysates are very low, generally in the ng/ml or even pg/ml range. An additional challenge is the very low volume of sample collected at each collection time and which can range from 1 to 30 μl only. Hence the objective was to develop and validate a rapid, accurate, precise, reproducible and highly sensitive LC–MS/MS method for the quantitative analysis of ketoprofen (KET) in dialystes following application of a topical gel product to the skin of human subjects. UPLC–MS/MS was used and KET was separated on an Acquity™ UPLC BEH C18 column (100 mm × 2.1 mm i.d., 1.7 μm) and analysed in negative-ion (NI) electrospray ionisation (ESI) mode. The mobile phase (MP) consisted of acetonitrile:methanol:water (60:20:20, v/v/v) under isocratic conditions at a flow rate of 0.3 ml/min. Samples were extracted using ethyl acetate with ibuprofen (IBU) as internal standard (IS) and the organic solvent was then evaporated to dryness and the residue re-constituted in methanol. 5 μl samples were injected and analysis was performed at ambient temperature 22 ± 0.5 °C. KET and IBU eluted at 1.07 and 1.49 min, respectively. KET and IBU responses were optimised at the transitions 253.00 > 209.00 and 205.00 > 161.00, respectively. Calibration curves were linear over the range 0.5–500 ng/ml with correlation coefficients > 0.999. The accuracy and precision of the method were found to be between 99.97% and 104.67% (R.S.D. < 2%) and the mean recovery of KET from normal saline was 88.03 ± 0.3% (R.S.D. < 2.20%). The LLOQ and LOD values were found to be 0.5 and 0.1 ng/ml respectively whereas the ULOD was set at 500 ng/ml. The method was successfully applied to determine the bioavailability of KET following application of topical KET gel, Fastum® gel, to the skin of human volunteers

Rapid and Precise Determination of Zero-Field Splittings by Terahertz Time-Domain Electron Paramagnetic Resonance Spectroscopy

Zero-field splitting (ZFS) parameters are fundamentally tied to the geometries of metal ion complexes. Despite their critical importance for understanding the magnetism and spectroscopy of metal complexes, they are not routinely available through general laboratory-based techniques, and are often inferred from magnetism data. Here we demonstrate a simple tabletop experimental approach that enables direct and reliable determination of ZFS parameters in the terahertz (THz) regime. We report time-domain measurements of electron paramagnetic resonance (EPR) signals associated with THz-frequency ZFSs in molecular complexes containing high-spin transition-metal ions. We measure the temporal profiles of the free-induction decays of spin resonances in the complexes at zero and nonzero external magnetic fields, and we derive the EPR spectra via numerical Fourier transformation of the time-domain signals. In most cases, absolute values of the ZFS parameters are extracted from the measured zero-field EPR frequencies, and the signs can be determined by zero-field measurements at two different temperatures. Field-dependent EPR measurements further allow refined determination of the ZFS parameters and access to the g-factor. The results show good agreement with those obtained by other methods. The simplicity of the method portends wide applicability in chemistry, biology and material science.Comment: 36 pages, 30 figures, 1 tabl

SOCS3 is a modulator of human macrophage phagocytosis

ACKNOWLEDGMENTS This work was supported by Kidney Research UK (Grant Number RP1/2012). The authors thank the staff of the Aberdeen Microscopy and Histology Core Facility for advice and technical assistance. The authors acknowledge and are grateful to all volunteers for donating blood for macrophage and neutrophil isolation.Peer reviewedPublisher PD

New Loop Representations for 2+1 Gravity

Since the gauge group underlying 2+1-dimensional general relativity is non-compact, certain difficulties arise in the passage from the connection to the loop representations. It is shown that these problems can be handled by appropriately choosing the measure that features in the definition of the loop transform. Thus, ``old-fashioned'' loop representations - based on ordinary loops - do exist. In the case when the spatial topology is that of a two-torus, these can be constructed explicitly; {\it all} quantum states can be represented as functions of (homotopy classes of) loops and the scalar product and the action of the basic observables can be given directly in terms of loops.Comment: 28pp, 1 figure (postscript, compressed and uuencoded), TeX, Pennsylvania State University, CGPG-94/5-

On the effect of heterovalent substitutions in ruthenocuprates

We discuss the properties of superconducting derivatives of the RuSr2GdCu2O8 (1212-type) ruthenocuprate, for which heterovalent doping has been achieved through partial substitution of Cu ions into the RuO2 planes (Ru1-xSr2GdCu2+xO8-d, 0<x<0.75, Tcmax=72 K for x=0.3-0.4) and Ce ions into the Gd sites (RuSr2Gd1-yCeyCu2O8, 0<y<0.1). The measurements of XANES, thermopower, and magnetization under external pressure reveal an underdoped character of all compounds. Muon spin rotation experiments indicate the presence of magnetic order at low temperatures (Tm=14-2 K for x=0.1-0.4). Properties of these two series lead us to the qualitative phase diagram for differently doped 1212-type ruthenocuprates. The difference in temperature of magnetic ordering found for superconducting and non-superconducting RuSr2GdCu2O8 is discussed in the context of the properties of substituted compounds. The high pressure oxygen conditions required for synthesis of Ru1-xSr2RECu2+xO8-d, have been extended to synthesis of a Ru1-xSr2Eu2-yCeyCu2+xO10-d series. The Cu->Ru doping achieved in these phases is found to decrease the temperature for magnetic ordering as well the volume fraction of the magnetic phase.Comment: Proceedings of the 3rd Polish-US Workshop on Magnetism and Superconductivity of Advanced Materials, July 14-19, 2002, Ladek Zdroj (Poland) to appear in Physica

Towards a large-scale quantum simulator on diamond surface at room temperature

Strongly-correlated quantum many-body systems exhibits a variety of exotic phases with long-range quantum correlations, such as spin liquids and supersolids. Despite the rapid increase in computational power of modern computers, the numerical simulation of these complex systems becomes intractable even for a few dozens of particles. Feynman's idea of quantum simulators offers an innovative way to bypass this computational barrier. However, the proposed realizations of such devices either require very low temperatures (ultracold gases in optical lattices, trapped ions, superconducting devices) and considerable technological effort, or are extremely hard to scale in practice (NMR, linear optics). In this work, we propose a new architecture for a scalable quantum simulator that can operate at room temperature. It consists of strongly-interacting nuclear spins attached to the diamond surface by its direct chemical treatment, or by means of a functionalized graphene sheet. The initialization, control and read-out of this quantum simulator can be accomplished with nitrogen-vacancy centers implanted in diamond. The system can be engineered to simulate a wide variety of interesting strongly-correlated models with long-range dipole-dipole interactions. Due to the superior coherence time of nuclear spins and nitrogen-vacancy centers in diamond, our proposal offers new opportunities towards large-scale quantum simulation at room temperatures

Interplay between collective expansion and Mach cone

By using a hybrid dynamical model which describes space-time evolution ofthe bulk medium, (mini-)jet propagation and interactions between medium and (mini-)jets, we study hydrodynamic responses to (mini-)jet propagation in high energy nuclear collisions. When an energetic jet traverses the bulk matter, it loses its energy into the matter and forms a Mach-cone like structure. On the other hand, the bulk matter expands radially due to pressure gradient. As a result, there happens an interplay between radial expansion and the Mach cone. We discuss possible phenomena and observables related with this in asymmetric gamma-jet events. We also discuss phenomena in which many mini-jets propagate the bulk matter at once in an event and calculate higher harmonics of azimuthal angle distribution

Dynamical slowing down in an ultrafast photo-induced phase transition

Complex systems, which consist of a large number of interacting constituents, often exhibit universal behavior near a phase transition. A slowdown of certain dynamical observables is one such recurring feature found in a vast array of contexts. This phenomenon, known as critical slowing down, is well studied mostly in thermodynamic phase transitions. However, it is less understood in highly nonequilibrium settings, where the time it takes to traverse the phase boundary becomes comparable to the timescale of dynamical fluctuations. Using transient optical spectroscopy and femtosecond electron diffraction, we studied a photo-induced transition of a model charge-density-wave (CDW) compound, LaTe$_3$. We observed that it takes the longest time to suppress the order parameter at the threshold photoexcitation density, where the CDW transiently vanishes. This finding can be quantitatively captured by generalizing the time-dependent Landau theory to a system far from equilibrium. The experimental observation and theoretical understanding of dynamical slowing down may offer insight into other general principles behind nonequilibrium phase transitions in many-body systems