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

Seeing Star Formation Regions with Gravitational Microlensing

We qualitatively study the effects of gravitational microlensing on our view of unresolved extragalactic star formation regions. Using a general gravitational microlensing configuration, we perform a number of simulations that reveal that specific imprints of the star forming region are imprinted, both photometrically and spectroscopically, upon observations. Such observations have the potential to reveal the nature and size of these star forming regions, through the degree of variability observed in a monitoring campaign, and hence resolve the star formation regions in distant galaxies which are too small to be probed via more standard techniques.Comment: 7 pages, 8 figures, ApJ accepte

Stripes of Partially Fluorinated Alkyl Chains: Dipolar Langmuir Monolayers

Stripe-like domains of Langmuir monolayers formed by surfactants with partially fluorinated lipid anchors (F-alkyl lipids) are observed at the gas-liquid phase coexistence. The average periodicity of the stripes, measured by fluorescence microscopy, is in the micrometer range, varying between 2 and 8 microns. The observed stripe-like patterns are stabilized due to dipole-dipole interactions between terminal -CF3 groups. These interactions are particularly strong as compared with non-fluorinated lipids due to the low dielectric constant of the surrounding media (air). These long-range dipolar interactions tend to elongate the domains, in contrast to the line tension that tends to minimize the length of the domain boundary. This behavior should be compared with that of the lipid monolayer having alkyl chains, and which form spherical micro-domains (bubbles) at the gas-liquid coexistence. The measured stripe periodicity agrees quantitatively with a theoretical model. Moreover, the reduction in line tension by adding traces (0.1 mol fraction) of cholesterol results, as expected, in a decrease in the domain periodicity.Comment: 20 pages, 4 fig

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