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

Massive low surface brightness galaxies

A multi-wavelength study of an extreme type of galaxy which will assist us in our attempts to understand the formation and evolution of galaxies was completed. In particular, a subset of low surface brightness (bar-mu(sub B) is approximately greater than 25 mag arcsec(sup -2)), giant galaxies (LSBG's) which contain large amounts of atomic gas (M(HI) is approximately greater than 10(exp 10) solar mass), have blue optical diameters similar to those of giant spiral galaxies, but which do not seem to have prodigious amounts of ongoing star formation were observed. Our sample was drawn from the first and second Palomar Sky Surveys. This population of galaxies has been largely ignored because of selection effects which make it difficult to detect optically. The question of how these massive systems differ from the higher surface brightness 'normal' spiral galaxies is addressed. Using B and R surface photometry, in conjunction with H-alpha, HI, CO-12, and far-infrared data, an attempt is made to determine if these galaxies had an early epoch of star formation that has since faded, have ongoing star formation with an unusual interplanetary magnetic field (IMF), or are perhaps galaxies which have never efficiently formed stars due to a lack of molecular clouds

Lunar International Observers Network operation during the Apollo 10 mission

Lunar International Observers Network operation during Apollo 10 missio

The Molecular Gas Distribution and Schmidt Law in M33

The relationship between the star formation rate and surface density of neutral gas within the disk of M33 is examined with new imaging observations of CO J=1-0 emission gathered with the FCRAO 14m telescope and IRAS HiRes images of the 60 micron and 100 micron emission. The Schmidt law, Sigma_SFR ~ Sigma_gas^n, is constructed using radial profiles of the HI 21cm, CO, and far infrared emission. A strong correlation is identified between the star formation rate and molecular gas surface density. This suggests that the condensation of giant molecular clouds is the limiting step to star formation within the M33 disk. The corresponding molecular Schmidt index, n_{mol}, is 1.36 +/- 0.08. The star formation rate has a steep dependence on total mass gas surface density, (Sigma_{HI}+Sigma_{H_2}), owing to the shallow radial profile of the atomic gas which dominates the total gas surface density for most radii. The disk pressure of the gas is shown to play a prominent role in regulating the molecular gas fraction in M33.Comment: 19 pages + 5 figures. Accepted for publication in Ap

Self-Perceived Health and Outlook Among the Rural Elderly

Differences in life outlook and self-perceived health often attributed to age differences among the elderly were found to be more accurately explained by education. The young-old (62-74 years) and the old-old (75 years and older) were compared among 495 elderly in two rural counties in western Arkansas. The old-old were more likely than the young-old to perceive their health as better than that of others their age. But when six variables including age were entered into a predictive model for self-perceived health, differences were explained by education. That is, those with better educations rated their health more positively. There was no difference between the two age groups in sick days, although the old-old reported more days hospitalized and trips to the doctor. However, no predictive model for health status measured was statistically significant. On measures of life satisfaction, the old-old were slightly more pessimistic than the young-old. But the age difference in life outlook was explained by education when the data were controlled for other variables. The customary division of the elderly into young-old and old-old is questioned, and policy implications of the findings are discussed

Large inverse tunneling magnetoresistance in Co2_2Cr0.6_{0.6}Fe0.4_{0.4}Al/MgO/CoFe magnetic tunnel junctions

Magnetic tunnel junctions with the layer sequence Co$_2$Cr$_{0.6}$Fe$_{0.4}$Al/MgO/CoFe were fabricated by magnetron sputtering at room temperature (RT). The samples exhibit a large inverse tunneling magnetoresistance (TMR) effect of up to -66% at RT. The largest value of -84% at 20 K reflects a rather weak influence of temperature. The dependence on the voltage drop shows an unusual behavior with two almost symmetric peaks at $\pm600$ mV with large inverse TMR ratios and small positive values around zero bias

A low-luminosity type-1 QSO sample; III. Optical spectroscopic properties and activity classification

We report on the optical spectroscopic analysis of a sample of 99 low-luminosity quasi-stellar objects (LLQSOs) at $z\leq 0.06$ base the Hamburg/ESO QSO survey (HES). The LLQSOs presented here offer the possibility of studying the faint end of the QSO population at smaller cosmological distances and, therefore, in greater detail. A small number of our LLQSO present no broad component. Two sources show double broad components, whereas six comply with the classic NLS1 requirements. As expected in NLR of broad line AGNs, the [S{\sc{ii}}]$-$based electron density values range between 100 and 1000 N$_{e}$/cm$^{3}$. Using the optical characteristics of Populations A and B, we find that 50\% of our sources with H$\beta$ broad emission are consistent with the radio-quiet sources definition. The remaining sources could be interpreted as low-luminosity radio-loud quasar. The BPT-based classification renders an AGN/Seyfert activity between 50 to 60\%. For the remaining sources, the possible star burst contribution might control the LINER and HII classification. Finally, we discuss the aperture effect as responsible for the differences found between data sets, although variability in the BLR could play a significant role as well.Comment: 22 pages; 5 tables; 17 figures; in press with A&

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