Virtual chemical reactions for drug design

Two methods for the fast, fragment-based combinatorial molecule assembly were developed. The software COLIBREE® (Combinatorial Library Breeding) generates candidate structures from scratch, based on stochastic optimization [1]. Result structures of a COLIBREE design run are based on a fixed scaffold and variable linkers and side-chains. Linkers representing virtual chemical reactions and side-chain building blocks obtained from pseudo-retrosynthetic dissection of large compound databases are exchanged during optimization. The process of molecule design employs a discrete version of Particle Swarm Optimization (PSO) [2]. Assembled compounds are scored according to their similarity to known reference ligands. Distance to reference molecules is computed in the space of the topological pharmacophore descriptor CATS [3]. In a case study, the approach was applied to the de novo design of potential peroxisome proliferator-activated receptor (PPAR gamma) selective agonists. In a second approach, we developed the formal grammar Reaction-MQL [4] for the in silico representation and application of chemical reactions. Chemical transformation schemes are defined by functional groups participating in known organic reactions. The substructures are specified by the linear Molecular Query Language (MQL) [5]. The developed software package contains a parser for Reaction-MQL-expressions and enables users to design, test and virtually apply chemical reactions. The program has already been used to create combinatorial libraries for virtual screening studies. It was also applied in fragmentation studies with different sets of retrosynthetic reactions and various compound libraries

Experimental active and passive dosimetry systems for the NASA Skylab program

Active and passive dosimetry instrumentation to measure absorbed dose, charged particle spectra, and linear energy transfer spectra inside the command module and orbital workshop on the Skylab program were developed and tested. The active dosimetry system consists of one integral unit employing both a tissue equivalent ionization chamber and silicon solid state detectors. The instrument measures dose rates from 0.2 millirad/hour to 25 rads/hour, linear energy transfer spectra from 2.8 to 42.4 Kev/micron, and the proton and alpha particle energy spectra from 0.5 to 75 Mev. The active dosimeter is equipped with a portable radiation sensor for use in astronaut on-body and spacecraft shielding surveys during passage of the Skylab through significant space radiations. Data are transmitted in real time or are recorded by onboard spacecraft tape recorder for rapid evaluation of the radiation levels. The passive dosimetry systems consist of twelve (12) hard-mounted assemblies, each containing a variety of passive radiation sensors which are recoverable at the end of the mission for analysis

Spectroscopic investigations of plasma properties quarterly summary report no. 2, 11 aug. - 10 nov. 1964

Performance of plasma source operated with helium - intensity and temperature profiles of source electronic instrumentation for detecting weak spectrum line

Experimental probing of the anisotropy of the empty p states near the Fermi level in MgB2

We have studied the Boron K-edge in the superconductor MgB2 by electron energy loss spectroscopy (EELS) and experimentally resolved the empty p states at the Fermi level that have previously been observed within an energy window of 0.8eV by soft x-ray absorption spectroscopy. Using angular resolved EELS, we find that these states at the immediate edge onset have pxy character in agreement with predictions from first-principle electronic structure calculations.Comment: 15 pages, 5 figure

A general interpolation scheme for thermal fluctuations in superconductors

We present a general interpolation theory for the phenomenological effects of thermal fluctuations in superconductors. Fluctuations are described by a simple gauge invariant extension of the gaussian effective potential for the Ginzburg-Landau static model. The approach is shown to be a genuine variational method, and to be stationary for infinitesimal gauge variations around the Landau gauge. Correlation and penetration lengths are shown to depart from the mean field behaviour in a more or less wide range of temperature below the critical regime, depending on the class of material considered. The method is quite general and yields a very good interpolation of the experimental data for very different materials.Comment: some misprints have been corrected in Eq.(15),(19); more references and comments have been adde

Evolution of Mass Functions of Coeval Stars through Wind Mass Loss and Binary Interactions

Accurate determinations of stellar mass functions and ages of stellar populations are crucial to much of astrophysics. We analyse the evolution of stellar mass functions of coeval main sequence stars including all relevant aspects of single- and binary-star evolution. We show that the slope of the upper part of the mass function in a stellar cluster can be quite different to the slope of the initial mass function. Wind mass loss from massive stars leads to an accumulation of stars which is visible as a peak at the high mass end of mass functions, thereby flattening the mass function slope. Mass accretion and mergers in close binary systems create a tail of rejuvenated binary products. These blue straggler stars extend the single star mass function by up to a factor of two in mass and can appear up to ten times younger than their parent stellar cluster. Cluster ages derived from their most massive stars that are close to the turn-off may thus be significantly biased. To overcome such difficulties, we propose the use of the binary tail of stellar mass functions as an unambiguous clock to derive the cluster age because the location of the onset of the binary tail identifies the cluster turn-off mass. It is indicated by a pronounced jump in the mass function of old stellar populations and by the wind mass loss peak in young stellar populations. We further characterise the binary induced blue straggler population in star clusters in terms of their frequency, binary fraction and apparent age.Comment: 21 pages, 22 figures, accepted for publication in Ap