Induced Ginibre ensemble of random matrices and quantum operations

A generalisation of the Ginibre ensemble of non-Hermitian random square matrices is introduced. The corresponding probability measure is induced by the ensemble of rectangular Gaussian matrices via a quadratisation procedure. We derive the joint probability density of eigenvalues for such induced Ginibre ensemble and study various spectral correlation functions for complex and real matrices, and analyse universal behaviour in the limit of large dimensions. In this limit the eigenvalues of the induced Ginibre ensemble cover uniformly a ring in the complex plane. The real induced Ginibre ensemble is shown to be useful to describe statistical properties of evolution operators associated with random quantum operations, for which the dimensions of the input state and the output state do differ.Comment: 2nd version, 34 pages, 5 figure

Preorganized tridentate analogues of mixed hydroxyoxime/carboxylate nickel extractants

Simple tridentate ligands can operate as Ni-extractants in the pH-dependent process: 2LHorg + NiSO4 ⇌ [(L)2Ni]org + H2SO4.</p

Überblick über die neueren Arbeiten auf dem Gebiet des Wasserstoff-und Tritiumverhaltens in Hochtemperaturreaktoren

This report comprises the contributions of members of the "Institut für Reaktor-Entwicklung" (IRE) to the "Und Seminar on Hydrogen and Tritium Behaviour in High Temperature Reactors", which was held March 8, 1978, at KFA Jülich. At the beginning the problem is introduced and the investigations at IRE related to this area are presented in their context. Then follow the individual papers on the subjects mentioned. At first the experiences with the operation of the experimental facility AUWARM and the newest results in the current testing program are discussed. Therafter the model investigations with hydrogen and deuterium on the problem of hydrogen- and tritium permeation are reported and a computer program for balancing tritium in pebble-bed-HTRs is described. Last notleast the studies on the behaviour of tritium in matrix graphite and the experiments on primary coolant purification by titanium gettering are shortly communicated. The results given in this report are preliminary informations on the actual status of the current investigations

One-component plasma on a spherical annulus and a random matrix ensemble

The two-dimensional one-component plasma at the special coupling \beta = 2 is known to be exactly solvable, for its free energy and all of its correlations, on a variety of surfaces and with various boundary conditions. Here we study this system confined to a spherical annulus with soft wall boundary conditions, paying special attention to the resulting asymptotic forms from the viewpoint of expected general properties of the two-dimensional plasma. Our study is motivated by the realization of the Boltzmann factor for the plasma system with \beta = 2, after stereographic projection from the sphere to the complex plane, by a certain random matrix ensemble constructed out of complex Gaussian and Haar distributed unitary matrices.Comment: v2, typos and references corrected, 24 pages, 1 figur

A theoretical entropy score as a single value to express inhibitor selectivity

<p>Abstract</p> <p>Background</p> <p>Designing maximally selective ligands that act on individual targets is the dominant paradigm in drug discovery. Poor selectivity can underlie toxicity and side effects in the clinic, and for this reason compound selectivity is increasingly monitored from very early on in the drug discovery process. To make sense of large amounts of profiling data, and to determine when a compound is sufficiently selective, there is a need for a proper quantitative measure of selectivity.</p> <p>Results</p> <p>Here we propose a new theoretical entropy score that can be calculated from a set of IC₅₀data. In contrast to previous measures such as the 'selectivity score', Gini score, or partition index, the entropy score is non-arbitary, fully exploits IC₅₀data, and is not dependent on a reference enzyme. In addition, the entropy score gives the most robust values with data from different sources, because it is less sensitive to errors. We apply the new score to kinase and nuclear receptor profiling data, and to high-throughput screening data. In addition, through analyzing profiles of clinical compounds, we show quantitatively that a more selective kinase inhibitor is not necessarily more drug-like.</p> <p>Conclusions</p> <p>For quantifying selectivity from panel profiling, a theoretical entropy score is the best method. It is valuable for studying the molecular mechanisms of selectivity, and to steer compound progression in drug discovery programs.</p

Key steps in the structure-based optimization of the hepatitis C virus NS3/4A protease inhibitor SCH503034

Crystal structures of protease/inhibitor complexes guided optimization of the buried nonpolar surface area thereby maximizing hydrophobic binding. The resulting potent tripeptide inhibitor is in clinical trials

Cobalamin in inflammation III — glutathionylcobalamin and methylcobalamin/adenosylcobalamin coenzymes: the sword in the stone? How cobalamin may directly regulate the nitric oxide synthases

Several mysteries surround the structure and function of the nitric oxide synthases (NOS). The NOS oxygenase domain structure is unusually open with a large area of solvent that could accommodate an unidentified ligand. The exact mechanism of the two-step five-electron monoxygenation of arginine to NG-hydroxy-L-arginine, thence to citrulline and nitric oxide (NO), is not clear, particularly as arginine/NG-hydroxy-L-arginine is bound at a great distance to the supposed catalytic heme Fe [III], as the anti-stereoisomer. The Return of the Scarlet Pimpernel Paper proposed that cobalamin is a primary indirect regulator of the NOS. An additional direct regulatory effect of the ‘base-off’ dimethylbenzimidazole of glutathionylcobalamin (GSCbl), which may act as a sixth ligand to the heme iron, promote Co-oriented, BH4/BH3 radical catalysed oxidation of L-arginine to NO, and possibly regulate the rate of inducible NOS/NO production by the NOS dimers, is further advanced. The absence of homology between the NOS and methionine synthase/methylmalonyl CoA mutase may enable GSCbl to regulate both sets of enzymes simultaneously by completely separate mechanisms. Thus, cobalamin may exert central control over both pro-and anti-inflammatory systems