In vitro drug sensitivity-gene expression correlations involve a tissue of origin dependency

A major concern of chemogenomics is to associate drug activity with biological variables. Several reports have clustered cell line drug activity profiles as well as drug activity-gene expression correlation profiles and noted that the resulting groupings differ but still reflect mechanism of action. The present paper shows that these discrepancies can be viewed as a weighting of drug-drug distances, the weights depending on which cell lines the two drugs differ in.     

Effects of echo time variation on perfusion assessment using dynamic susceptibility contrast MR imaging at 3 tesla

The implications of changing the echo time of a gradient-echo echo planar imaging sequence applied to dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) for perfusion imaging at 3T were investigated. Four echo times in the range of 21 to 45 ms were examined in a total of 17 patients who received a dose of 0.1 mmol/kg bodyweight Gadobutrol (Gadovist, 1.0 mmol/ml). As the primary optimization parameter, the concentration-to-noise ratio (SNRc) was selected as it takes effects of variations in baseline as well as in signal drop into account. In an analysis of gray matter, white matter and arterial regions of interest, SNRc showed the highest values for the shortest applied echo time in all cases. Maps of regional cerebral blood volume (rCBV) and blood flow (rCBF) were calculated using deconvolution based on singular value decomposition. The quality of rCBF and rCBV images was judged to be good or excellent in all cases, independent of the echo time. Calculated gray matter/white matter ratios of rCBF and rCBV displayed no significant dependence on the applied echo time. Considering the better SNRc and arterial signal saturation aspects, we found that the shortest investigated echo time was the superior one. We thus suggest that short echo times should be applied, taking technical limitations and clinical demands into consideration.     

High-capacity composite adsorbents for nucleic acids

Cytopore™ is a bead-shaped, macroporous and easily compressible cellulose-based anion-exchange material intended for cultivation of anchor-dependent animal cells. Reticulated vitreous carbon (RVC) is a strong, non-compressible, high voidage (97%) matrix material that can be cut to desired geometrical shapes. Cytopore and RVC were combined to cylindrical composites (25 mm × 10 mm) fitted inside chromatography columns. The composite combined the advantageous properties of both its constituents, making it suitable for column chromatography. The composite could withstand very high flow rates without compaction of the bed (>25 column volumes/min; 4000 cm h⁻¹). Chromatography runs with tracers showed a low HETP value (0.3 mm), suggesting that pore flow was in operation. The dynamic binding capacities (10% breakthrough) per gram of dry weight Cytopore were determined for several compounds including DNA and RNA and were found to be 240–370 mg/g. The composite was used to isolate pUC 18-type plasmids from a cleared alkaline lysate in a good yield. Confocal microscopy studies showed that plasmids were bound not only to the surface of the Cytopore material but also within the matrix walls, thus offering an explanation to the very high binding capacities observed. The concept of using a composite prepared from a mechanically weak, high-binding material and a strong scaffold material may be applied to other systems as well.     

Nitrogen-doped carbon nanotubes: growth, mechanism and structure

Nitrogen-doped bamboo-structured carbon nanotubes have been successfully grown using a series of cobalt/molybdenum catalysts. The morphology and structure of the nanotubes were analysed by transmission electron microscopy and Raman spectroscopy. The level of nitrogen doping, as determined by X-ray photoelectron spectroscopy, was found to range between 0.5 to 2.5 at.%. The growth of bamboo-structured nanotubes in the presence of nitrogen, in preference to single-walled and multi-walled nanotubes, was due to the greater binding energy of nitrogen for cobalt in the catalyst compared to the binding strength of carbon to cobalt, as determined by density functional theory.     

Evidence for phase separation of ethanol-water mixtures at the hydrogen terminated nanocrystalline diamond surface

Interactions between ethanol-water mixtures and a hydrophobic hydrogen terminated nanocrystalline diamond surface, are investigated by sessile drop contact angle measurements. The surface free energy of the hydrophobic surface, obtained with pure liquids, differs strongly from values obtained by ethanol-water mixtures. Here, a model which explains this difference is presented. The model suggests that, due to a higher affinity of ethanol for the hydrophobic surface, when compared to water, a phase separation occurs when a mixture of both liquids is in contact with the H-terminated diamond surface. These results are supported by a computational study giving insight in the affinity and related interaction at the liquid-solid interface.     

Visualization of β‐carotene and starch granules in plant cells using CARS and SHG microscopy

Information on the content and bioavailability of provitamin A carotenoids, such as β‐carotene, in plant foods is of great interest due to the widespread vitamin A deficiency in developing countries. While the amount of β‐carotene can readily be quantified with analytical techniques, there is limited information on β‐carotene morphology in native plant materials. Here, we introduce nonlinear microscopy for three‐dimensional, label‐free imaging of carotenoids in fresh and thermally treated plant tissues, providing quantitative information at single‐aggregate level and detailed insight into their distribution. Carotenoids in orange‐fleshed sweet potato (OFSP), carrot, and mango were visualized by coherent anti‐Stokes Raman scattering (CARS) microscopy and, in the case of OFSP, related to the plant‐matrix morphology by simultaneous second‐harmonic generation (SHG) microscopy of starch granules. Sizes, shapes, densities, and location of different types of carotenoid bodies were quantified. While OFSP and carrot showed heterogeneous rod‐shaped bodies with high carotenoid densities indicated by higher CARS signals, the carotenoid‐filled lipid droplets in mango appeared as homogeneous low‐density aggregates of rounded shape. In addition, β‐carotene densities and morphologies in OFSP were studied after thermal processing, showing that the bodies remain intact despite significant changes of the surrounding starch granules. Copyright © 2010 John Wiley & Sons, Ltd.     

X-Ray Photoelectron Spectral (XPS) Studies of Molybdenum (0) and Tungsten (0) Dinitrogen Complexes

The X-ray photoelectron spectra of M(N₂)₂ (dppe)₂, M(N₂)₂ (PMePh₂)₄ and M(N₂)₂ (PMe₂Ph)₄; where M=W or Mo, Ph is phenyl, Me is methyl and dppe is (Ph)₂P-CH₂-CH₂-P(Ph)₂; have been investigated. The N(1s), P(2p_3/2), Mo(3d_5/2) and W(4f_7/2) binding energies do not show significant differences between these complexes. The N(1s) signals show the separation of 1.3-1.4 eV.     

Posterior contraction rates for the Bayesian approach to linear ill-posed inverse problems

We consider a Bayesian nonparametric approach to a family of linear inverse problems in a separable Hilbert space setting with Gaussian noise. We assume Gaussian priors, which are conjugate to the model, and present a method of identifying the posterior using its precision operator. Working with the unbounded precision operator enables us to use partial differential equations (PDE) methodology to obtain rates of contraction of the posterior distribution to a Dirac measure centered on the true solution. Our methods assume a relatively weak relation between the prior covariance, noise covariance and forward operator, allowing for a wide range of applications.     

Weak convergence of finite element approximations of linear stochastic evolution equations with additive noise

A unified approach is given for the analysis of the weak error of spatially semidiscrete finite element methods for linear stochastic partial differential equations driven by additive noise. An error representation formula is found in an abstract setting based on the semigroup formulation of stochastic evolution equations. This is then applied to the stochastic heat, linearized Cahn-Hilliard, and wave equations. In all cases it is found that the rate of weak convergence is twice the rate of strong convergence, sometimes up to a logarithmic factor, under the same or, essentially the same, regularity requirements.     

Designed protein binders in combination with nanocrystalline diamond for use in high-sensitivity biosensors

A platform for diagnostic applications showing signal-to-noise ratios that by far surpass those of traditional bioanalytical test formats has been developed. It combines the properties of modified nanocrystalline diamond (NCD) surfaces and those of polyethylene oxide and polypropylene oxide based block copolymers for surface passivation and binder conjugation with a new class of synthetic binders for proteins. The NCD surfaces were fluorine-, hydrogen-, or oxygen-terminated prior to further biofunctionalization and the surface composition was characterized by X-ray photoelectron spectroscopy. In a proof of principle demonstration targeting the C-reactive protein, an ELISA carried out using an F-terminated diamond surface showed a signal-to-noise ratio of 3,900 which compares well to the signal-to-noise of 89 obtained in an antibody-based ELISA on a polystyrene microtiter plate, a standard test format used in most life science laboratories today. The increase in signal-to-noise ratio is to a large extent the result of extremely efficient passivation of the diamond surface. The results suggest that significant improvements can be obtained in standardized test formats using new materials in combination with new types of chemical coatings and receptor molecules.