Measurement and stability of FTY720 in human whole blood by high-performance liquid chromatography-atmospheric pressure chemical ionization-tandem mass spectrometry

We report here a validated method for the quantification of a new immunosuppressant drug FTY720, using HPLC-tandem mass spectrometry. Whole blood samples (500 mu l) were subjected to liquid-liquid extraction, in the presence of an internal standard (Y-32919). Mass spectrometric detection was by selected reaction monitoring with an atmospheric pressure chemical ionization source in positive ionization mode (FTY720: m/z 308.3 -> 255.3). The assay was linear from 0.2 to 25 mu g/l (r(2) > 0.997, n = 5). The inter- and intra-day analytical recovery and imprecision for quality control samples (0.5, 7 and 15 mu g/l) were 95.8-103.2 and < 5.5%, respectively. At the lower limit of quantification (0.2 mu g/l) the interand intra-day analytical recovery was 99.0-102.8% with imprecision of < 7.6% (n = 5). The assay had a mean relative recovery of 100.5 +/- 5.8% (n = 15). Extracted samples were stable for 16 h. IFTY720 quality control samples were stable at room temperature for 16 h at 4 degrees C for at least 8 days and when taken through at least three freeze-thaw cycles. In conclusion, the method described displays analytical performance characteristics that are suitable for pharmacokinetic studies in humans. (c) 2006 Elsevier B.V. All rights reserved.

Wavelength-division and spatial multiplexing using tandem interferometers for Bragg grating sensor networks

We present a new method for the interrogation of large arrays of Bragg grating sensors. Eight gratings operating between the wavelengths of 1533 and 1555 nm have been demultiplexed. An unbalanced Mach—Zehnder interferometer illuminated by a single low-coherence source provides a high-phase-resolution output for each sensor, the outputs of which are sequentially selected in wavelength by a tunable Fabry-Perot interferometer. The minimum detectable strain measured was 90 ne-vHz at 7 Hz for a wavelength of 1535 nm.

Cracking in the welding of cupro-nickel alloys

The problem of variation in weld crack susceptibility caused by small variations in alloy and impurity elements for the 70-30 cupro-nickel alloy has been investigated. Both wrought and cast versions of the alloy have been studied, the main techniques employed being the Varestraint test and weld thermal simulation. In the wrought alloys, cracking has been found to occur mainly in the weld metal, whilst in the cast alloys cracking is extensive in both weld metal and heat affected zone. The previously reported effects of certain impurities (P,S,Si) in increasing cracking have been confirmed, and it has also been shown that Ti and Zr may both have a crack promoting effect at levels commonly found in cupro-nickels, whilst C can interact with several of the other elements investigated to produce a beneficial effect. The testing carried out using the weld thermal simulator has shown that a relationship does exist between hot ductility and weld cracking. In particular, the absence of the peak in ductility in the range 1100°C-900°C on cooling from a temperature near to the solidus is indicative of a highly crack susceptible alloy. Principal practical implications of the investigation concern the relationship of weld metal cracking to alloy composition, especially the level of certain impurities. It would appear that the upper limits permitted by the alloy specifications are unrealistically high. The introduction of lower impurity limits would alleviate the current problems of variability in resistance to cracking during welding.

The copper cladding of steel by the submerged arc welding method

The literature available on submerged arc welding of copper and copper alloys, submerged arc welding with strip electrodes, and related areas has been reviewed in depth. Copper cladding of mild steel substrates by deposition from strip electrodes using the submerged arc welding process has been successful. A wide range of parameters, and several fluxes have been investigated. The range of deposit compositions is 66.4% Cu to 95.7% Cu. The weld beads have been metallographically examined using optical and electron microscopy. Equating weld beads to a thermodynamical equivalent of iron has proven to be an accurate and simplified means of handling quantitative data for multicomponent welds. Empirical equations derived using theoretical considerations characterize the weld bead dimensions as functions of the welding parameters and hence composition. The melting rate for strip electrodes is dependent upon the current-voltage product. Weld nugget size is increased by increased thermal transfer efficiencies resulting from stirring which is current dependent. The presence of Fe2O3 in a flux has been demonstrated to diminish electrode melting rate and drastically increase penetration, making flux choice the prime consideration in cladding operations. A theoretical model for welding with strip electrodes and the submerged arc process is presented.

Gas-metal reactions and porosity in the inert gas arc welding of copper

A study has been made of the effects of welding and material variables on the occurrence of porosity in tungsten inert gas arc welding of copper. The experiments were based on a statistical design and variables included, welding current, welding speed, arc atmosphere composition, inert gas flow rate, weld preparation, and base material. The extent of weld metal porosity was assessed by density measurement and its morphology by X-ray radiography and metallography. In conjunction with this the copper-steam reaction has been investigated under conditions of controlled atmosphere arc melting. The welding experiments have shown that the extent of steam porosity is increased by increased water vapour content of the arc atmosphere, increased oxygen content of the base material and decreased welding speed. The arc melting experiments have shown that the steam reaction occurs in the body of the weld pool and proceeds to an apparent equi1ibrium state appropriate to to its temperature, the hydrogen and oxygen being supplied by the dissociation of water vapour in the arc atmosphere. It has been shown conclusively that nitrogen porosity can occur in the tungsten inert gas arc welding of copper and that this porosity can be eliminated by using filler wires containing small amounts of aluminum and titanium. Since it has been shown to be much more difficult to produce sound butt welds than melt runs it has been concluded that the porosity associated with joint fit up is due to nitrogen entrained into tho arc atmosphere. Clearly atmospheric entrainment would also, to a much lesser extent, involve water vapour. From a practical welding point of view it has thus been postulated that use of a filler wire containing small amounts of aluminum and/or titanium would eliminate both forms of porosity since these elements are both strongJy deoxidising and denitriding.

40-Gbaud 16-QAM transmitter using tandem IQ modulators with binary driving electronic signals

We propose a novel 16-quadrature amplitude modulation (QAM) transmitter based on two cascaded IQ modulators driven by four separate binary electrical signals. The proposed 16-QAM transmitter features scalable configuration and stable performance with simple bias-control. Generation of 16-QAM signals at 40 Gbaud is experimentally demonstrated for the first time and visualized with a high speed constellation analyzer. The proposed modulator is also compared to two other schemes. We investigate the modulator bandwidth requirements and tolerance to accumulated chromatic dispersion through numerical simulations, and the minimum theoretical insertion attenuation is calculated analytically.

Resistance welding of coated steels

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The upstream Variable Number Tandem Repeat polymorphism of the monoamine oxidase type A gene influences trigeminal pain-related evoked responses

Monoamines have an important role in neural plasticity, a key factor in cortical pain processing that promotes changes in neuronal network connectivity. Monoamine oxidase type A (MAOA) is an enzyme that, due to its modulating role in monoaminergic activity, could play a role in cortical pain processing. The X-linked MAOA gene is characterized by an allelic variant of length, the MAOA upstream Variable Number Tandem Repeat (MAOA-uVNTR) region polymorphism. Two allelic variants of this gene are known, the high-activity MAOA (HAM) and low-activity MAOA (LAM). We investigated the role of MAOA-uVNTR in cortical pain processing in a group of healthy individuals measured by the trigeminal electric pain-related evoked potential (tPREP) elicited by repeated painful stimulation. A group of healthy volunteers was genotyped to detect MAOA-uVNTR polymorphism. Electrical tPREPs were recorded by stimulating the right supraorbital nerve with a concentric electrode. The N2 and P2 component amplitude and latency as well as the N2-P2 inter-peak amplitude were measured. The recording was divided into three blocks, each containing 10 consecutive stimuli and the N2-P2 amplitude was compared between blocks. Of the 67 volunteers, 37 were HAM and 30 were LAM. HAM subjects differed from LAM subjects in terms of amplitude of the grand-averaged and first-block N2-P2 responses (HAM>LAM). The N2-P2 amplitude decreased between the first and third block in HAM subjects but not LAM subjects. The MAOA-uVNTR polymorphism seemed to influence the brain response in a repeated tPREP paradigm and suggested a role of the MAOA as a modulator of neural plasticity related to cortical pain processing. Monoamines have an important role in neural plasticity, a key factor in cortical pain processing that promotes changes in neuronal network connectivity. Monoamine oxidase type A (MAOA) is an enzyme that, due to its modulating role in monoaminergic activity, could play a role in cortical pain processing. © 2014 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.