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.     

Stock market crashes are outliers

We call attention against what seems to be a widely held misconception according to which large crashes are the largest events of distributions of price variations with fat tails. We demonstrate on the Dow Jones Industrial Average that with high probability the three largest crashes in this century are outliers. This result supports the suggestion that large crashes result from specific amplification processes that might lead to observable pre-cursory signatures. Received and Revised: 30 November 1997 / Accepted: 8 December 1997     

Non-deterministic programming

This paper presents some results of R. W. Floyd (1966). He proposes inclusion of additional features in present programming languages to be able to express in a convenient way algorithms based on the technique of backtrack described by Golomb and Baumert (1965). Floyd proposes a way of implementation. Here we suggest an alternative method and present results obtained from an experimental implementation.     

Enzymatic degradation of model cellulose films

Enzymatic degradation of model cellulose films prepared by a spin-coating technique was investigated by ellipsometry. The cellulose films were prior to degradation characterized by ellipsometry, contact angle measurements, ESCA (electron spectroscopy for chemical analysis) and AFM (atomic force microscopy). At enzyme addition to preformed cellulose films an initial adsorption was observed, which was followed by a total interfacial mass decrease due to enzymatic degradation of the cellulose films. The degradation rate was found to be constant during an extended time of hours, whereafter the degradation leveled off. In parallel to the decreased interfacial mass, the cellulose degradation resulted in a thinner and more dilute interfacial film. At long degradation times, however, there was an expansion of the cellulose film. The enzyme concentration affected the degradation rate significantly, with a faster degradation at a higher enzyme concentration. The effects of pH, temperature, ionic strength and stirring rate in the cuvette were also investigated.     

Pointwise convergence in probability of general smoothing splines

Establishing the convergence of splines can be cast as a variational problem which is amenable to a \(\Gamma \)-convergence approach. We consider the case in which the regularization coefficient scales with the number of observations, n, as \(\lambda _n=n^{-p}\). Using standard theorems from the \(\Gamma \)-convergence literature, we prove that the general spline model is consistent in that estimators converge in a sense slightly weaker than weak convergence in probability for \(p\le \frac{1}{2}\). Without further assumptions, we show this rate is sharp. This differs from rates for strong convergence using Hilbert scales where one can often choose \(p>\frac{1}{2}\).