Computer tomography based reconstruction of metal matrix syntactic foams

In order to create 3D (three-dimensional) models for finite element calculations it is necessary to reconstruct the structure of metal foam composites reinforced by hollow ceramic spheres. A new algorithm was developed for this reconstruction work. This algorithm is based on the investigation of sphericity of the shapes found on CT (computer tomograph) layer records. Using this algorithm a 3D CAD (computer aided design) model of acceptable precision can be constructed

The hypergiant HR 8752 evolving through the yellow evolutionary void

Context. We study the time history of the yellow hypergiant HR 8752 based on high-resolution spectra (1973-2005), the observed MK spectral classification data, B - V- and V-observations (1918-1996) and yet earlier V-observations (1840-1918).<br>Aims. Our local thermal equilibrium analysis of the spectra yields accurate values of the effective temperature (T-eff), the acceleration of gravity (g), and the turbulent velocity (v(t)) for 26 spectra. The standard deviations average are 82 K for T-eff, 0.23 for log g, and 1.1 km s(-1) for v(t).<br>Methods. A comparison of B-V observations, MK spectral types, and T-eff-data yields E(B-V), "intrinsic" B-V, T-eff, absorption A(V), and the bolometric correction BC. With the additional information from simultaneous values of B-V, V, and an estimated value of R, the ratio of specific absorption to the interstellar absorption parameter E(B - V), the "unreddened" bolometric magnitude m(bol),(0) can be determined. With Hipparcos distance measurements of HR 8752, the absolute bolometric magnitude M-bol,M-0 can be determined.<br>Results. Over the period of our study, the value of T-eff gradually increased during a number of downward excursions that were observable over the period of sufficient time coverage. These observations, together with those of the effective acceleration g and the turbulent velocity v(t), suggest that the star underwent a number of successive gas ejections. During each ejection, a pseudo photosphere was produced of increasingly smaller g and higher v(t) values. After the dispersion into space of the ejected shells and after the restructuring of the star's atmosphere, a hotter and more compact photosphere became visible. From the B - V and V observations, the basic stellar parameters, T-eff, log M/M-circle dot, log L/L-circle dot, and log R/R-circle dot are determined for each of the observational points. The results show the variation in these basic stellar parameters over the past near-century.<br>Conclusions. We show that the atmospheric instability region in the HR-diagram that we baptize the yellow evolutionary void actually consists of two parts. We claim that the present observations show that HR 8752 is presently climbing out of the "first" instability region and that it is on its way to stability, but in the course of its future evolution it still has to go through the second potential unstable region

The extended atmosphere and evolution of the RV Tau star R Scuti

We analyze ISO/SWS spectra of the RV Tau star R Scuti. The infrared spectra are dominated by H2O emission bands. The near- and mid-infrared excess is attributed to H2O; the dust contribution is less important. We also identify CO, SiO and CO2 bands. The various molecular emission bands originate from an extended atmosphere, an atmosphere above the photosphere. The extended atmosphere of R Sct is formed from matter which gradually have lifted up from the photosphere through the pulsations of the star. In contrast to the abundant molecules around the star, the silicate dust feature is weak and the dust mass-loss rate is only 10^{-11} solar mass per year. This implies that there might be a process to inhibit dust formation from molecules. RV Tau stars are commonly considered as post-AGB stars. While a detached dust envelope around R Sct is consistent with such an interpretation, we show that its period evolution is slower than expected. We argue that R Sct may be a thermal-pulsing AGB star, observed in a helium-burning phase.Comment: 10 pages, 7 figures, accepted by A&

Drug Discovery Using Chemical Systems Biology: Weak Inhibition of Multiple Kinases May Contribute to the Anti-Cancer Effect of Nelfinavir

Nelfinavir is a potent HIV-protease inhibitor with pleiotropic effects in cancer cells. Experimental studies connect its anti-cancer effects to the suppression of the Akt signaling pathway, but the actual molecular targets remain unknown. Using a structural proteome-wide off-target pipeline, which integrates molecular dynamics simulation and MM/GBSA free energy calculations with ligand binding site comparison and biological network analysis, we identified putative human off-targets of Nelfinavir and analyzed the impact on the associated biological processes. Our results suggest that Nelfinavir is able to inhibit multiple members of the protein kinase-like superfamily, which are involved in the regulation of cellular processes vital for carcinogenesis and metastasis. The computational predictions are supported by kinase activity assays and are consistent with existing experimental and clinical evidence. This finding provides a molecular basis to explain the broad-spectrum anti-cancer effect of Nelfinavir and presents opportunities to optimize the drug as a targeted polypharmacology agent

The Mycobacterium tuberculosis Drugome and Its Polypharmacological Implications

We report a computational approach that integrates structural bioinformatics, molecular modelling and systems biology to construct a drug-target network on a structural proteome-wide scale. The approach has been applied to the genome of Mycobacterium tuberculosis (M.tb), the causative agent of one of today's most widely spread infectious diseases. The resulting drug-target interaction network for all structurally characterized approved drugs bound to putative M.tb receptors, we refer to as the ‘TB-drugome’. The TB-drugome reveals that approximately one-third of the drugs examined have the potential to be repositioned to treat tuberculosis and that many currently unexploited M.tb receptors may be chemically druggable and could serve as novel anti-tubercular targets. Furthermore, a detailed analysis of the TB-drugome has shed new light on the controversial issues surrounding drug-target networks [1]–[3]. Indeed, our results support the idea that drug-target networks are inherently modular, and further that any observed randomness is mainly caused by biased target coverage. The TB-drugome (http://funsite.sdsc.edu/drugome/TB) has the potential to be a valuable resource in the development of safe and efficient anti-tubercular drugs. More generally the methodology may be applied to other pathogens of interest with results improving as more of their structural proteomes are determined through the continued efforts of structural biology/genomics