Photodissociation tandem mass spectrometry at 266 nm of an aliphatic peptide derivatized with phenyl isothiocyanate and 4-sulfophenyl isothiocyanate

Photodissociation (PD) tandem mass spectra have been obtained at 266 nm for the protonated molecules of a tryptic peptide, ASHLGLAR, and of its phenyl isothiocyanate and 4-sulfophenyl isothiocyanate derivatives, generated by matrix-assisted laser desorption/ionization. Derivatization with the aromatic chromophores greatly reduced the intensity of the laser required for efficient PD. Major fragment ions observed in the three spectra are quite similar. General features of the PD tandem mass spectra and their potential utility for analytical purposes are discussed.     

Mass-analyzed threshold ionization study of vinyl bromide cation in the first excited electronic state using vacuum-ultraviolet radiation generated by four-wave mixing in Hg

The vibrational spectrum of the vinyl bromide cation in the first excited electronic state A 2A' was obtained by one-photon mass-analyzed threshold ionization (MATI) spectroscopy. The use of an improved vacuum-ultraviolet radiation source based on four-wave sum frequency mixing in Hg resulted in excellent sensitivity for MATI signals. From the MATI spectrum, the ionization energy to the A 2A' state of the cation was determined to be 10.9150+/-0.0006 eV. Nearly complete vibrational assignments for the MATI peaks were possible by utilizing the vibrational frequencies and Franck-Condon factors calculated at the density-functional theory (DFT) and time-dependent DFT/B3LYP levels with the 6-311+G(df,p) basis set.     

A molecular approach to rationally constructing specific fluorogenic substrates for the detection of acetylcholinesterase activity in live cells,mice brains and tissues

Acetylcholinesterase (AChE) is an extremely critical hydrolase tightly associated with neurological diseases. Currently, developing specific substrates for imaging AChE activity still remains a great challenge due to the interference from butyrylcholinesterase (BChE) and carboxylesterase (CE). Herein, we propose an approach to designing specific substrates for AChE detection by combining dimethylcarbamate choline with a self-immolative scaffold. The representative P10 can effectively eliminate the interference from CE and BChE. The high specificity of P10 has been proved via imaging AChE activity in cells. Moreover, P10 can also be used to successfully map AChE activity in different regions of a normal mouse brain, which may provide important data for AChE evaluation in clinical studies. Such a rational and effective approach can also provide a solid basis for designing probes with different properties to study AChE in biosystems and another way to design specific substrates for other enzymes.

In this work, a new approach was developed for designing the representative P10 with high selectivity and sensitivity for imaging AChE activity in the cells and normal mouse brain.     

Evidence for unfolding and refolding of gas-phase cytochrome <Emphasis Type="Italic">c</Emphasis> ions in a Paul trap

The folding pathways of gas-phase cytochrome c ions produced by electrospray ionization have been studied by an ion trapping/ion mobility technique that allows conformations to be examined over extended timescales (10 ms to 10 s). The results show that the +9 charge state emerges from solution as a compact structure and then rapidly unfolds into several substantially more open structures, a transition that requires 30-60 ms; over substantially longer timescales (250 ms to 10 s) elongated states appear to refold into an array of folded structures. The new folded states are less compact than those that are apparent during the initial unfolding. Apparently, unfolding to highly open conformations is a key step that must occur before +9 ions can sample more compact states that are stable at longer times.     

Determination of PF‐04620110, a novel inhibitor of diacylglycerol acyltransferase‐1, in rat plasma using liquid chromatography–tandem mass spectrometry and its application in pharmacokinetic studies

In this study, we developed a method for the determination of PF‐04620110 (2‐{(1r,4r)‐4‐[4‐(4‐amino‐5‐oxo‐7,8‐dihydropyrimido[5,4‐f][1,4]oxazepin‐6(5H)‐yl)phenyl]cyclohexyl}acetic acid), a novel diacylglycerol acyltransferase 1 (DGAT‐1) inhibitor, in rat plasma and validated it using liquid chromatography–tandem mass spectrometry (LC‐MS/MS). Rat plasma samples were processed following a protein precipitation method by using acetonitrile and were then injected into an LC‐MS/MS system for quantification. PF‐04620110 and imipramine (internal standard) were separated using a Hypersil Gold C₁₈ column, with a mixture of acetonitrile and 10 mm ammonium formate (90:10, v/v) as the mobile phase. The ion transitions monitored in positive‐ion mode [M + H]⁺ of multiple‐reaction monitoring were m/z 397.0 → 260.2 for PF‐04620110 and m/z 280.8 → 86.0 for imipramine. The detector response was specific and linear for PF‐04620110 at concentrations within the range 0.05–50 µg/mL and the signal‐to‐noise ratios for the samples were ≥10. The intra‐ and inter‐day precision and accuracy of the method matched the acceptance criteria for assay validation. PF‐04620110 was stable under various processing and/or handling conditions. PF‐04620110 concentrations in the rat plasma samples could be measured up to 24 h after intravenous or oral administration of PF‐04620110, suggesting that the assay is useful for pharmacokinetic studies in rats. Copyright © 2013 John Wiley & Sons, Ltd.     

Issue Information

An integrated finite element method (FEM) is proposed to simulate incompressible two‐phase flows with surface tension effects, and three different surface tension models are applied to the FEM to investigate spurious currents and temporal stability. A Q2Q1 element is adopted to solve the continuity and Navier–Stokes equations and a Q2‐iso‐Q1 to solve the level set equation. The integrated FEM solves pressure and velocity simultaneously in a strongly coupled manner; the level set function is reinitialized by adopting a direct approach using interfacial geometry information instead of solving a conventional hyperbolic‐type equation. In addition, a consistent continuum surface force (consistent CSF) model is utilized by employing the same basis function for both surface tension and pressure variables to damp out spurious currents and to estimate the accurate pressure distribution. The model is further represented as a semi‐implicit manner to improve temporal stability with an increased time step. In order to verify the accuracy and robustness of the code, the present method is applied to a few benchmark problems of the static bubble and rising bubble with large density and viscosity ratios. The Q2Q1‐integrated FEM coupled with the semi‐implicit consistent CSF demonstrates the significantly reduced spurious currents and improved temporal stability. The numerical results are in good qualitative and quantitative agreements with those of the existing studies. Copyright © 2015 John Wiley & Sons, Ltd.     

On $$\epsilon $$ ϵ -solutions for robust semi-infinite optimization problems

Positivity - In this paper, we consider semi-infinite optimization problems involving a convex objective function and infinitely many convex constraint functions with data uncertainty, and give its...