CEMS of Sb+ implanted stainless steels

Martensitic transformations have been analysed in a series of antimony implanted austenitic stainless steels using CEMS. The implanted samples contain about 70 vols martensite, which is considerably more than can be formed conventionally by plastic deformation or cooling below the martensite start temperature. CEM spectra from implantation induced martensite and from martensite formed in conventional processes are virtually identical. In both cases the hyperfine field is ≈ 25T.     

Analytical and numerical study on grating depth effects in grating coupled waveguide sensors

The in-coupling process for grating-coupled planar optical waveguide sensors is investigated in the case of TE waves. A simple analytical model based on the Rayleigh–Fourier–Kiselev method is applied to take into account the depth of the grating coupler, which is usually neglected in the modeling. Analytical expressions are derived both for the position and width of the in-coupling peaks to illustrate the effects of grating depth on the guided mode resonances in grating coupled waveguide sensors. Numerical computations verify the model for shallow gratings both in terms of peak shape and position and provide the limitations for the analytical formulas.     

High-performance size-exclusion chromatographic procedure for the determination of fluoresceinyl isothiocyanate dextrans of various molecular masses in biological media

A high-performance size-exclusion chromatographic procedure, using Nucleosil Diol, for the quantitative analysis of fluoresceinyl isothiocyanate dextrans of various molecular masses (10,000-150,000) in biological media was developed. The influence of the molecular mass and the degree of substitution of the conjugates on the chromatographic behaviour are discussed. In addition to quantitation, the molecular mass of the conjugates with degree of substitution below 1.6 could be estimated from the chromatograms. Linear standard calibration curves were obtained at concentrations down to 0.050 micrograms ml-1 in rabbit plasma and urine and homogenates of rabbit liver, lymph node and muscle when the derivative (degree of substitution 0.85) was monitored by fluorescence detection (lambda ex = 493 nm, lambda em = 520 mm). The fluoresceinyl isothiocyanate dextrans were found to be stable for more than three days at 37 degrees in all biological media under investigation. A pH-rate profile for the alkaline hydrolysis of fluoresceinyl isothiocyanate dextrans was constructed. The applicability of the method to pharmacokinetic studies was demonstrated by recording the plasma concentration-time profile of a fluoresceinyl isothiocyanate dextran T-70 conjugate following intravenous injection to a rabbit. In relation to future pharmacokinetic investigations on dextran conjugates, the results reported indicate that labelling of the parent dextran with fluoresceinyl isothiocyanate and monitoring of the fluoresceinyl isothiocyanate dextran conjugate throughout the organism using the described method is a promising development.     

Interaction between superconducting vortices and a Bloch wall in ferrite garnet films

A theoretical model for how Bloch walls occurring in in-plane magnetized ferrite garnet films can serve as efficient magnetic micromanipulators is presented. As an example, the walls' interaction with Abrikosov vortices in a superconductor in close contact with a garnet film is analyzed within the London approximation. The model explains how vortices are attracted to such walls, and excellent quantitative agreement is obtained for the resulting peaked flux profile determined experimentally in NbSe(2) using high-resolution magneto-optical imaging of vortices. In particular, this model, when generalized to include charged magnetic walls, explains the counterintuitive attraction observed between vortices and a Bloch wall of opposite polarity.     

Dramatic role of critical current anisotropy on flux avalanches in MgB2 films

Anisotropic penetration of magnetic flux in MgB(2) films grown on vicinal sapphire substrates is investigated using magneto-optical imaging. Regular penetration above 10 K proceeds more easily along the substrate surface steps, the anisotropy of the critical current being 6%. At lower temperatures the penetration occurs via abrupt dendritic avalanches that preferentially propagate perpendicular to the surface steps. This inverse anisotropy in the penetration pattern becomes dramatic very close to 10 K where all flux avalanches propagate in the strongest pinning direction. The observed behavior is fully explained using a thermomagnetic model of the dendritic instability.     

Chemogenomic discovery of allosteric antagonists at the GPRC6A receptor

GPRC6A is a Family C G protein-coupled receptor recently discovered and deorphanized by our group. This study integrates chemogenomic ligand inference, homology modeling, compound synthesis, and pharmacological mechanism-of-action studies to disclose two noticeable results of methodological and pharmacological character: (1) chemogenomic lead identification through the first, to our knowledge, ligand inference between two different GPCR families, Families A and C; and (2) the discovery of the most selective GPRC6A allosteric antagonists discovered to date. The unprecedented inference of?pharmacological activity across GPCR families provides proof-of-concept for in?silico approaches against Family C targets based on Family A templates, greatly expanding the prospects of successful drug design and discovery. The antagonists were tested against a panel of seven Family A and C G protein-coupled receptors containing the chemogenomic binding sequence motif where some of the identified GPRC6A antagonists showed some activity. However, three compounds with at least ～3-fold selectivity for GPRC6A were discovered, which present a significant step forward compared with the previously published GPRC6A antagonists, calindol and NPS 2143, which both display ～30-fold selectivity for the calcium-sensing receptor compared to GPRC6A. The antagonists constitute novel research tools toward investigating the signaling mechanism of the GPRC6A receptor at the cellular level and serve as initial ligands for further optimization of potency and selectivity enabling future ex?vivo/in?vivo pharmacological studies.     

Protamine neutralisation of low molecular weight heparins and their oligosaccharide components

Protamine sulphate is an effective inhibitor of heparin and is used clinically to neutralise both low molecular weight heparins (LMWH) and unfractionated heparin (UFH). However, protamine sulphate does not fully counter the anti-Xa effect of LMWH, even in excess (>40 μg to 1 IU/ml). To investigate the molecular basis for this observation, the residual potencies in the presence and absence of plasma as well as the molecular weight profiles of commercial LMWH neutralised with increasing amounts of protamine were measured. Materials over 5000 Da are preferentially neutralised by protamine. To further investigate this molecular weight dependence, monodisperse oligosaccharides were prepared from three commercial LMWHs. The specific anti-Xa activity for the fractions increased with molecular weight, and was found to vary between the three preparations for oligosaccharides of the same molecular weight. Our results indicate that protamine sulphate neutralisation is largely dependent on molecular weight, leading to the implication that LMWHs containing a larger proportion of small oligosaccharides will not be as effectively neutralised. Protamine sulphate neutralisation of any given LMWH is also affected by the specific anticoagulant activities of its low molecular weight components, which varies between LMWH products, presumably with the method of manufacture.