Optimizing an ultrafast generic high-performance liquid chromatography/tandem mass spectrometry method for faster discovery pharmacokinetic sample throughput

For higher throughput screening, where the number of new chemical entities (NCEs) to test is rapidly increasing, fast sample turnaround time is essential. In order to increase efficiency a generic high-performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS) method, with a cycle time of 85 s (42 injections/h), was created. This was accomplished through the use of a 1-min ballistic gradient and the optimization of the autosampler. The gradient was optimized by varying the organic mobile phase concentration and examining its ballistic characteristics with respect to matrix ion suppression and compound retention time. The autosampler time could be reduced by optimizing several parameters and by determining the source of most of the carryover in order to reduce the number of syringe and injector washes. Finally, the reliability of the new generic method is demonstrated by comparison of sample data with a standard 2-min linear gradient method that showed that the data sets were well correlated. For plasma AUC (ng.h/mL) of 28 NCEs, the regression line had a slope of 0.92 and the R2 was 0.929. The described method was found to be useful for both rat plasma and tissue samples.     

Analysis of dust and surface swab samples for octachlorodibenzo-p-dioxin and heptachlorodibenzo-p-dioxins by fused silica capillary GC with EC detection

A method is described for the analysis of contaminated building dust samples and surface swab samples for octachlorodibenzo-p-dioxin (OCDD) and heptachlorodibenzo-p-dioxins (HpCDDs). The samples were analyzed by fused silica capillary GC combined with electron capture detection. Analysis was preceded by a short HPLC cleanup step designed to remove polychlorinated biphenyls (PCBs) and other compounds that might interfere. The method was found to work successfully on surface swab and dust samples known to contain PCBs, OCDD, and HpCDDs. The overall recovery of the analysis procedure for OCDD was found to be approximately 80%. The detection limit for the method was sample dependent, but for one typical set of surface swab samples was 0.2 μg/m² of OCDD.     

Baryon antibaryon production in the central region at 85 GeV/c

In a search for glueballs and exotic states decaying into baryons and antibaryons we have investigated the production of baryon antibaryon pairs produced centrally in the reactions π⁺/pp → π⁺/p(X ⁰)p at 85 GeV/c. In particular, channels whereX ⁰ goes to \(p\bar p,p\bar p\pi ^ + \pi ^ - ,p\bar p2\pi ^ + 2\pi ^ - \) and \(\Lambda \bar \Lambda \) have been observed. No significant new structure is observed in the mass spectra.     

Azimuthal anisotropy of photon and charged parti cle emissionin 208Pb + 208Pb collisions at 158 $\ cdot A$ GeV/ c

The azimuthal distributions of photons and charged particles with respect to the event plane are investigated as a function of centrality in ²⁰⁸Pb + ²⁰⁸Pb collisions at 158 GeV/c in the WA98 experiment at the CERN SPS. The anisotropy of the azimuthal distributions is characterized using a Fourier analysis. For both the photon and charged particle distributions the first two Fourier coefficients are observed to decrease with increasing centrality. The observed anisotropies of the photon distributions compare well with the expectations from the charged particle measurements for all centralities.Received: 22 May 2004, Revised: 14 April 2005, Published online: 4 May 2005PACS: 25.75.Dw     

Dilepton and trilepton production by antineutrinos and neutrinos in neon

A sample of over 25,000 fully measured neutrino and antineutrino charged current interactions in BEBC includes 192 dilepton candidates. The prompt signal after subtraction of background is 41 ±7µ⁺ e ^-, 35±7µ⁺µ^- events from \(\bar v\) interactions, and 32±7µ^-µ⁺ events from ν interactions. There are 2 trileptons, µ^-µ^- e ⁺ and µ^-µ^-µ⁺. Results are compared with other experimental data and with the standard model. Limits to prompt like sign µ⁺ e ⁺, µ⁺µ⁺ and µ^-µ^- signals are given and compared with other experiments and with theoretical calculations.     

Implementation of the moving particle semi-implicit method on GPU

The Moving Particle Semi-implicit (MPS) method performs well in simulating violent free surface flow and hence becomes popular in the area of fluid flow simulation. However, the implementations of searching neighbouring particles and solving the large sparse matrix equations (Poisson-type equation) are very time-consuming. In order to utilize the tremendous power of parallel computation of Graphics Processing Units (GPU), this study has developed a GPU-based MPS model employing the Compute Unified Device Ar...     

Investigation of the profiling depth in matrix-assisted laser desorption/ionization imaging mass spectrometry

Matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry is generally considered to be a surface analysis technique. In this report, the profiling depth of imaging mass spectrometry was examined. MALDI matrix solution was found to be able to gain access to the tissue interior and extract analyte molecules to the tissue surface. As a consequence, prazosin, a small molecule pharmaceutical compound, located as deep as 40 microm away from the surface was readily detected after matrix application. Likewise, cytochrome c, a 12 kDa protein, was also detectable from the tissue interior. Moreover, for prazosin, not only the extent of matrix effect, but also the extraction efficiency of the matrix solvent appeared to be dependent on the type of tissue. These results indicated that experimental conditions that decrease the matrix solvent evaporation during matrix application may increase analyte extraction efficiency and hence sensitivity of the analysis. Furthermore, thin sections should be used to avoid differential extraction efficiency of matrix solvent in different tissues for whole-body analysis.     

An adeno-associated viral vector transduces the rat hypothalamus and amygdala more efficient than a lentiviral vector

Background  

This study compared the transduction efficiencies of an adeno-associated viral (AAV) vector, which was pseudotyped with an AAV1 capsid and encoded the green fluorescent protein (GFP), with a lentiviral (LV) vector, which was pseudotyped with a VSV-G envelop and encoded the discosoma red fluorescent protein (dsRed), to investigate which viral vector transduced the lateral hypothalamus or the amygdala more efficiently. The LV-dsRed and AAV1-GFP vector were mixed and injected into the lateral hypothalamus or into the amygdala of adult rats. The titers that were injected were 1 × 10⁸ or 1 × 10⁹ genomic copies of AAV1-GFP and 1 × 10⁵ transducing units of LV-dsRed.