Evaluation of an Accurate Mass Approach for the Simultaneous Detection of Drug and Metabolite Distributions via Whole-Body Mass Spectrometric Imaging

In drug discovery and development, in vitro absorption and metabolism assays along with in vivo pharmacokinetic (PK), pharmacodynamic (PD), and toxicokinetic (TK) studies are used to evaluate a potential drug candidate. More recently, imaging mass spectrometry approaches have been successfully reported to aid in the preclinical assessment of drug candidates, resulting in the rapid and noteworthy acceptance of the technique in pharmaceutical research. Traditionally, drug distribution studies via mass spectrometric imaging (MSI) are performed as targeted MS/MS analyses, where the analytes of interest, drug and/or metabolite, are known before the imaging experiment is performed. The study presented here describes a whole-body mass spectrometric imaging (WB-MSI) approach using a hybrid MALDI-LTQ-Orbitrap-MS to detect the distribution of reserpine at 2 h post a 20 mg/kg oral dose. This study effectively demonstrates the utility of obtaining accurate mass measurements across a wide mass range combined with postprocessing tools to efficiently identify drug and metabolite distributions without the need for any a priori knowledge.     

Solution-processed zinc tetrabenzoporphyrin thin-films and transistors

Thin-films and organic field-effect transistors fabricated from a solution-processable precursor of zinc tetrabenzoporphyrin (ZnTBP) are reported. Amorphous, insulating precursor films were deposited by spin-casting and thermally converted into polycrystalline, semiconducting thin-films comprising grains on the order of 5 μm in diameter. Thin-film X-ray diffraction indicates a monoclinic unit cell with molecules arranged in a herringbone pattern, which in conjunction with optical and atomic force microscopy indicate a thin-film with grains comprised of randomly oriented ZnTBP aggregates. Optical absorption measurements display broad absorption with bands characteristic of a D_4h symmetric porphyrin molecule. Organic field-effect transistors displayed field-effect mobilities on the order of 10^− 2 cm²/V s and ON-/OFF-current ratios exceeding 10².     

The predominant role of collagen in the nucleation, growth, structure and orientation of bone apatite

The involvement of collagen in bone biomineralization is commonly admitted, yet its role remains unclear. Here we show that type I collagen in?vitro can initiate and orientate the growth of carbonated apatite mineral in the absence of any other vertebrate extracellular matrix molecules of calcifying tissues. We also show that the collagen matrix influences the structural characteristics on the atomic scale, and controls the size and the three-dimensional distribution of apatite at larger length scales. These results call into question recent consensus in the literature on the need for Ca-rich non-collagenous proteins for collagen mineralization to occur in vivo. Our model is based on a collagen/apatite self-assembly process that combines the ability to mimic the in vivo extracellular fluid with three major features inherent to living bone tissue, that is, high fibrillar density, monodispersed fibrils and long-range hierarchical organization.     

Plasma functionalization of silicon carbide crystalline nanoparticles in a novel low pressure powder reactor

In order to functionalize silicon carbide nanopowders with carboxylic groups, an r.f. (13.56 MHz) low pressure plasma reactor has been developed so that particles can be stirred during the processing to try to coat them on their whole surface. Coatings in an O₂/hexamethyldisilazane (HMDSN) mixture have first been optimized on flat substrates; X-ray Photoelectron Spectroscopy (XPS) analysis showed that the O₂/HMDSN gas mixture resulted in a coating evolving from a polymer-like structure to a more inorganic SiO_x-like structure as the oxygen ratio increased. For a large O₂/HMDSN value, carboxylic groups were detected on the sample surface. Silicon carbide nanoparticles have then been plasma processed in such a reactive atmosphere. XPS, Time of Flight Secondary Ion Mass Spectroscopy (ToF-SIMS) and Transmission Electron Microscopy (TEM) analyses evidenced the surface modification of the processed powder and confirmed the grafting of carboxylic groups.     

Localized high resolution electrochemistry and multifunctional imaging: scanning electrochemical cell microscopy

We describe highly localized electrochemical measurements and imaging using a simple, mobile theta pipet cell. Each channel (diameter <500 nm) of a tapered theta pipet is filled with electrolyte solution and a Ag/AgCl electrode, between which a bias is applied, resulting in a conductance current across a thin meniscus of solution at the end of the pipet, which is typically deployed in air or a controlled gaseous environment. When the position of the pipet normal to a surface of interest is oscillated, an oscillating component in the conductance current is generated when the meniscus at the end of the probe comes into contact with the surface and undergoes periodic (reversible) deformation, so as to modulate the solution resistance. This oscillating current component can be used to maintain gentle contact of the solution from the pipet cell with the surface and as a set point for high resolution topographical imaging with the pipet. Simultaneously, the mean conductance current that flows between the pipet channels can be measured and is sensitive to the local nature of the interface, informing one, for example, on wettability and ion flow into or out of the surface investigated. Furthermore, conductor or semiconductor surfaces can be connected as a working electrode, with one of the electrodes in the pipet serving as a quasi-reference electrode. This pipet cell then constitutes part of a dynamic electrochemical cell, with which direct voltammetric-amperometric imaging can be carried out simultaneously with conductance and topographical imaging. This provides multifunctional electrochemical maps of surfaces and interfaces at high spatial resolution. The prospects for the use of this new methodology widely are highlighted through exemplar studies and a brief discussion of future applications.     

A nanometre-sized porous phase in iron-carbon-boron system

A porous phase is detected in a Fe-0.28 wt.%C-0.1 wt.%B alloy. The porous phase is mainly located at the grain boundary region and the pore size ranges from about 10 nm to 500 nm. The chemical composition of the porous phase is very close to Fe₃(B_0.7C_0.3) with an orthorhombic lattice. The result shows an opportunity to produce bulk steel matrix composites with a porous second phase.     

Examining the neural correlates of choice behavior in a gambling task using steady state topography.

The present study investigated the behavioral and neuropsychological characteristics of decision-making behavior during a gambling task as well as how these characteristics may relate to the Somatic Marker Hypothesis and the Frequency of Gain model. The applicability to intertemporal choice was also discussed. Patterns of card selection during a computerized interpretation of the Iowa Gambling Task were assessed for 10 men and 10 women. Steady State Topography was employed to assess cortical processing throughout this task. Results supported the hypothesis that patterns of card selection were in line with both theories. As hypothesized, these 2 patterns of card selection were also associated with distinct patterns of cortical activity, suggesting that intertemporal choice may involve the recruitment of right dorsolateral prefrontal cortex for somatic labeling, left fusiform gyrus for object representations, and the left dorsolateral prefrontal cortex for an analysis of the associated frequency of gain or loss. It is suggested that processes contributing to intertemporal choice may include inhibition of negatively valenced options, guiding decisions away from those options, as well as computations favoring frequently rewarded options. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Sicher zündende,langzeitstabile Kaltkathode

Long term stable cold cathode with reliable ignition Cold cathodes gauges have been used in various areas of vacuum technology for decades. Their unique properties make them the method of choice even despite the residual magnetic field, poor ignition characteristics in the UHV‐region and long term stability. In other applications they do not significantly shorten the maintenance intervals. However, especially in the UHV or XHV region these properties lead to an extinguishing of cold cathode discharge. Considering the underlying processes and their correlation in this contribution an improved cold cathode will be presented. The measured data show a residual magnetic field of 1 mT in close vicinity to the gauge and an extended operating pressure range down to the 10^?12 mbar region. Furthermore the ignition characteristics were improved to < 60 s at 1×10^?9 mbar.     

Influence of potassium on the competition between methane and ethane in steam reforming over Pt supported on yttrium-stabilized zirconia

The effect of addition of potassium to Pt supported on yttrium-stabilized zirconia (PtYSZ) catalyst for steam reforming of methane, ethane and methane/ethane mixtures was explored. Addition of potassium has a positive effect on preferential steam reforming of methane in mixtures of methane and ethane over Pt/YSZ catalysts. The activity of potassium-modified catalysts increased with time-on-stream during steam reforming of mixtures of methane and ethane, while the ratio of reaction rates of methane and ethane remained constant. Most importantly, it was demonstrated that the presence of potassium prevents competition between methane and ethane during steam reforming. The reaction rate ratio in methane/ethane mixtures is changed from preferential ethane reforming on PtYSZ towards preferential methane conversion as a result of addition of potassium.