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.     

Role of nearby charges on the electronic structure of π-conjugated molecules: symmetric versus asymmetric charge distributions in oligo(p-phenyleneethynylene)

Oligo(p-phenyleneethynylene)s (OPEs) are conjugated oligomers of great interest within materials science and molecular electronics on account of their highly applicable electronic and optical properties. Here we use gas-phase action spectroscopy to elucidate how the intrinsic electronic properties of these chromophores are affected by nearby charges. An OPE3 chromophore with two nearby ammonium groups was synthesized. This molecule and a related OPE3 with only one amine protonation site were transferred to the gas phase by electrospray ionization and subjected to action spectroscopy. Ions were bunched in a 14-pole ion trap, accelerated to 50-keV kinetic energies, mass-to-charge selected by a magnet, and photoexcited in a crossed-beam configuration. Fragment ions were finally mass-analyzed by an electrostatic analyzer. The setup enables photodissociation mass spectrometry and action spectroscopy on the microsecond time scale. The gas-phase absorption of the mono- and dication was measured and compared to that of neutral chromophores in solution. Similar absorption was found for neutral chromophores (in solution) and the dication (in gas phase or solution), whereas the monocation absorbs at lower energies in the gas phase. Simple electrostatic considerations lead to an energy difference like the one found from the experiment. The work presented here addresses how the electronic properties of a π-conjugated system are affected by nearby charges, a question of fundamental interest in, for example, molecular electronics.     

One-pot synthesis of cyclopentadienyl endcapped poly(2-ethyl-2-oxazoline) and subsequent ambient temperature Diels-Alder conjugations

An efficient method for the preparation of cyclopentadienyl endcapped poly(2-ethyl-2-oxazoline) (PEtOx-Cp) via cationic ring-opening polymerization utilizing sodium cyclopentadienide as a termination agent is presented. Subsequent Diels-Alder reactions with N-substituted maleimides proceed quantitatively at ambient temperature. A block copolymer (PEtOx-b-PEG) is prepared employing maleimide terminated poly(ethylene glycol).     

Unraveling the similarity of the photoabsorption of deprotonated p-coumaric acid in the gas phase and within the photoactive yellow protein

Using advanced QM/MM methods, the surprisingly negligible shift of the lowest-lying bright electronic excitation of the deprotonated p-coumaric acid (pCA(-)) within the photoactive yellow protein (PYP) is shown to stem from a subtle balance between hypsochromic and bathochromic effects. More specifically, it is found that the change in the excitation energy as a consequence of the disruption of the planarity of pCA(-) inside PYP is nearly canceled out by the shift induced by the intermolecular interactions of the chromophore and the protein as a whole. These results provide important insights about the primary absorption and the tuning of the chromophore by the protein environment in PYP.     

Runge–Kutta Lawson schemes for stochastic differential equations

In this paper, we present a framework to construct general stochastic Runge–Kutta Lawson schemes. We prove that the schemes inherit the consistency and convergence properties of the underlying Runge–Kutta scheme, and confirm this in some numerical experiments. We also investigate the stability properties of the methods and show for some examples, that the new schemes have improved stability properties compared to the underlying schemes.

     

Femtosecond laser excitation of dielectric materials: experiments and modeling of optical properties and ablation depths

Modeling of the interaction between a dielectric material and ultrashort laser pulses provides the temporal evolution of the electronic excitation and the optical properties of the dielectric. Experimentally determined reflectances and ablation depths for sapphire are compared to the calculations. A decrease in reflectance at high fluences is observed experimentally, which demonstrates the necessity of a temperature-dependent electron scattering rate in the model. The comparison thus provides new constraints on the optical parameters of the model.     

A Dynamic Two-Phase Pore-Scale Model of Imbibition

We present a dynamic pore-scale network model of imbibition, capable of calculating residual oil saturation for any given capillary number, viscosity ratio, contact angle, and aspect ratio. Our goal is not to predict the outcome of core floods, but rather to perform a sensitivity analysis of the above-mentioned parameters, except from the viscosity ratio. We find that contact angle, aspect ratio, and capillary number all have a significant influence on the competition between piston-like advance, leading to high recovery, and snap-off, causing oil entrapment. Due to significant CPU-time requirements we did not incorporate long-range correlations among pore and throat sizes in our network, but were limited to small-range correlations. Consequently, the gradual suppression of snap-off occurs within one order of magnitude of the capillary number. At capillary numbers around 10⁸ - 10⁷ snap-off has been entirely inhibited, in agreement with results obtained by Blunt (1997) who used a quasi-static model. For higher aspect ratios, the effect of rate and contact angle is more pronounced.     

An instability of the Godunov scheme

We construct a solution to a 2 × 2 strictly hyperbolic system of conservation laws, showing that the Godunov scheme [13] can produce an arbitrarily large amount of oscillations. This happens when the speed of a shock is close to rational, inducing a resonance with the grid. Differently from the Glimm scheme or the vanishing‐viscosity method, for systems of conservation laws our counterexample indicates that no a priori BV bounds or L¹‐stability estimates can in general be valid for finite difference schemes. © 2006 Wiley Periodicals, Inc.     

A uniqueness result related to the stability of explicit Runge-Kutta methods

The polynomial associated with the largest disk of stability of anm-stage explict Runge-Kutta method of orderp is unique.     

MR microscopy of water diffusion tensor in biological systems

Diffusion tensor imaging (DTI) of the control and mechanically injured spinal cord of a ratin vitro andin vivo are reported.In vitro experiments were done on a home-built 6.4 T magnetic resonance microscope. Results for formaline-fixed samples show significant differences in diffusion tensor components between gray matter and white matter of the control spinal cord. Moreover, it is shown that already 6–10 min after the injury DTI can detect changes in water diffusion in areas extending far beyond the region of primary tissue damage.In vivo experiments were performed using a 9.4 T Magnex magnet and Bruker Medspec imaging system. Good-quality DTI images, free from motion artifacts were obtained. Results from control samples confirm differences in water diffusion between white matter and gray matter, observedin vitro. In vivo experiments show that characteristic changes in water diffusion observedin vitro 6–10 min after injury are preserved 60–360 min after injury, without significant alteration during this time.