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

Implications of the isotope effects on the magnetization, magnetic torque and susceptibility

We analyze the magnetization, magnetic torque and susceptibility data of La2-xSrxCu(16,18)O4 and YBa2(63,65)CuO7-x near Tc in terms of the universal 3D-XY scaling relations. It is shown that the isotope effect on Tc mirrors that on the anisotropy. Invoking the generic behavior of the anisotropy the doping dependence of the isotope effects on the critical properties, including Tc, correlation lengths and magnetic penetration depths are traced back to a change of the mobile carrier concentration.Comment: 5 pages, 3 figure

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

Reconstruction of Cluster Masses using Particle Based Lensing I: Application to Weak Lensing

We present Particle-Based Lensing (PBL), a new technique for gravitational lensing mass reconstructions of galaxy clusters. Traditionally, most methods have employed either a finite inversion or gridding to turn observational lensed galaxy ellipticities into an estimate of the surface mass density of a galaxy cluster. We approach the problem from a different perspective, motivated by the success of multi-scale analysis in smoothed particle hydrodynamics. In PBL, we treat each of the lensed galaxies as a particle and then reconstruct the potential by smoothing over a local kernel with variable smoothing scale. In this way, we can tune a reconstruction to produce constant signal-noise throughout, and maximally exploit regions of high information density. PBL is designed to include all lensing observables, including multiple image positions and fluxes from strong lensing, as well as weak lensing signals including shear and flexion. In this paper, however, we describe a shear-only reconstruction, and apply the method to several test cases, including simulated lensing clusters, as well as the well-studied ``Bullet Cluster'' (1E0657-56). In the former cases, we show that PBL is better able to identify cusps and substructures than are grid-based reconstructions, and in the latter case, we show that PBL is able to identify substructure in the Bullet Cluster without even exploiting strong lensing measurements. We also make our codes publicly available.Comment: Accepted for publication in ApJ; Codes available at http://www.physics.drexel.edu/~deb/PBL.htm ; 12 pages,9 figures, section 3 shortene

On the occurrence of Berezinskii-Kosterlitz-Thouless behavior in highly anisotropic cuprate superconductors

The conflicting observations in the highly anisotropic Bi2Sr2CaCu2O8+x, vidence for BKT behavior emerging from magnetization data and smeared 3D-xy behavior, stemming form the temperature dependence of the magnetic in-plane penetration depth are traced back to the rather small ratio, gsic+/gsic-=0.45, between the c-axis correlation length probed above (+) and below (-) Tc, and the comparatively large anisotropy. The latter leads to critical amplitudes gsic0+,-which are substantially smaller than the distance between two CuO2 double layers. In combination with gsic+/gsic-=0.45 and in contrast to the situation below Tc the c-axis correlation length gsic exceeds the distance between two CuO2 double layers very close to Tc only. Below this narrow temperature regime where 3D-xy fluctuations dominate, there is then an extended temperature regime where the units with two CuO2 double layers are nearly uncoupled so that 2D thermal fluctuations dominate and BKT features are observable.Comment: 4 pages, 4 figure

The Skewness of the Aperture Mass Statistic

We present simple formulae for calculating the skewness and kurtosis of the aperture mass statistic for weak lensing surveys which is insensitive to masking effects of survey geometry or variable survey depth. The calculation is the higher order analog of the formula given by Schneider et al (2002) which has been used to compute the variance of the aperture mass from several lensing surveys. As our formula requires the three-point shear correlation function, we also present an efficient tree-based algorithm for measuring it. We show how our algorithm would scale in computing time and memory usage for future lensing surveys. Finally, we apply the procedure to our CTIO survey data, originally described in Jarvis et al (2003). We find that the skewness is positive (inconsistent with zero) at the 2 sigma level. However, the signal is too noisy from this data to usefully constrain cosmology.Comment: 16 pages, accepted by MNRAS. Minor revisions; this replacement matches the accepted versio

Thickness dependence of linear and quadratic magneto-optical Kerr effect in ultrathin Fe(001) films

Magneto-optical Kerr effect (MOKE) magnetometry is one of the most widely employed techniques for the characterization of ferromagnetic thin-film samples. Some information, such as coercive fields or anisotropy strengths can be obtained without any knowledge of the optical and magneto-optical (MO) properties of the material. On the other hand, a quantitative analysis, which requires a precise knowledge of the material's index of refraction n and the MO coupling constants K and G is often desirable, for instance for the comparison of samples, which are different with respect to ferromagnetic layer thicknesses, substrates, or capping layers. While the values of the parameters n and the linear MO coupling parameter K reported by different authors usually vary considerably, the relevant quadratic MO coupling parameters G of Fe are completely unknown. Here, we report on measurements of the thickness dependence (0-60nm) of the linear and quadratic MOKE in epitaxial bcc-Fe(001) wedge-type samples performed at a commonly used laser wavelength of 670nm. By fitting the thickness dependence we are able to extract a complete set of parameters n, K, (G11 - G12), and G44 for the quantitative description of the MOKE of bcc-Fe(001). We find sizable different n, K, and G parameters for films thinner than about 10nm as compared to thicker films, which is indicative of a thickness dependence of the electronic properties or of surface contributions to the MOKE. The effect size of the quadratic MOKE is found to be about a third of the record values recently reported for Co2FeSi.Comment: 8 pages, 5 figure