Computer-Aided Search for 5-Arylideneimidazolone Anticancer Agents Able To Overcome ABCB1-Based Multidrug Resistance

ABCB1 modulation is an interesting strategy in the search for new anticancer agents that can overcome multidrug resistance (MDR). Hence, 17 new 5-arylideneimidazolones containing an amine moiety, as potential ABCB1 inhibitors, were designed, synthesized, and investigated. The series was tested in both parental (PAR) and multidrug-resistant (MDR) ABCB1-overexpressing T-lymphoma cancer cells using cytotoxicity assays. The ABCB1-modulating activity was examined in rhodamine 123 accumulation tests, followed by Pgp-Glo™ Assay to determine the influence of the most active compounds on ATPase activity. Lipophilic properties were assessed both, in silico and experimentally (RP-TLC). Pharmacophore-based molecular modelling toward ABCB1 modulation was performed. The studies allowed the identification of anticancer agents (p-fluorobenzylidene derivatives) more potent than doxorubicin, with highly selective action on MDR T-lymphoma cells (selectivity index >40). Most of the investigated compounds showed ABCB1-modulating action; in particular, two 5-benzyloxybenzylidene derivatives displayed activity nearly as strong as that of tariquidar.     

Possible effects of site isolation in antimony oxide-modified vanadia/titania catalysts for selective oxidation of o-xylene

Titania-supported vanadia catalysts were modified by addition of antimony oxide for application in o-xylene selective oxidation to phthalic anhydride. It was shown that active and selective catalysts can be prepared by ball-milling mixtures of powders of TiO₂, V₂O₅and Sb₂O₃followed by calcination. X-ray photoelectron spectroscopy proves the formation of highly dispersed overlayers of vanadium oxide and antimony oxide, in which V⁵⁺is partially reduced to lower oxidation states and Sb³⁺is partially oxidized to Sb⁵⁺. Antimony oxide segregated into the outermost surface layers. It is therefore inferred that the presence of the antimony oxide modifier spatially separates V–O species and leads to site isolation which may be responsible for the positive effect of the modifier for the catalyst's selectivity.     

Examining the dimensionality of genuine multipartite entanglement

Entanglement in high-dimensional many-body systems plays an increasingly vital role in the foundations and applications of quantum physics. In the present paper, we introduce a theoretical concept which allows to categorize multipartite states by the number of degrees of freedom being entangled. In this regard, we derive computable and experimentally friendly criteria for arbitrary multipartite qudit systems that enable to examine in how many degrees of freedom a mixed state is genuine multipartite entangled.     

Towards robust multi-cue integration for visual tracking

Abstract. Even though many of today's vision algorithms are very successful, they lack robustness, since they are typically tailored to a particular situation. In this paper, we argue that the principles of sensor and model integration can increase the robustness of today's computer-vision systems substantially. As an example, multi-cue tracking of faces is discussed. The approach is based on the principles of self-organization of the integration mechanism and self-adaptation of the cue models during tracking. Experiments show that the robustness of simple models is leveraged significantly by sensor and model integration.     

Generation and Quantification of Ultrafine Particles through Terpene/Ozone Reaction in a Chamber Setting

Terpene/ozone reactions produce gas- and condensed-phase products and thus contribute to both indoor and outdoor aerosol. These reactions may be important in indoor settings, where terpenes are generated from indoor sources and ambient ozone can reach significant levels. Moreover, airway irritation has been observed in mice exposed to terpene oxidation products (OPs). The aim of this study was to characterize a system for generating and quantifying ultrafine particles formed through terpene/ozone reactions in preparation for inhalation toxicology experiments. Two common monoterpenes, f -pinene and d -limonene, and a hemiterpene, isoprene, were investigated. Ozone and gas-phase terpene were introduced continuously into a reaction flow tube, from which reaction products entered a plexiglass chamber. Particle number, mass, and size distribution (～15-750 nm) were monitored in the chamber for various reactant concentrations and air exchange rates (AERs). In all experiments, ozone was the limiting reagent and the reaction rate was much more rapid than the AER. Particles formed rapidly and in high concentrations in the pinene and limonene systems. Particle formation was slower in the isoprene system and fewer particles were formed; moreover, particle diameters were smaller. In all 3 systems, progressive growth of particles was observed due to condensation and coagulation processes. The isoprene system displayed instability with respect to aerosol characteristics and did not reach steady-state conditions. In the pinene system, ozone concentration was a strong predictor of steady-state particle number and mass concentration and particle diameter. The particle number was greater at higher AERs, but particles were smaller. This study is the first to incorporate measurement of ultrafine particles formed from terpene/ozone reactions into a controlled exposure chamber setting. Following system characterization, we will conduct mouse exposures to further investigate the respiratory effects of gas- and particle-phase terpene OPs.     

Simultaneous Detection of Positive and Negative Ions From Single Airborne Particles by Real-time Laser Mass Spectrometry

ABSTRACT

The instrumental setup used for simultaneous bipolar ion detection in on-line single-particle analysis by laser mass spectrometry is described. Particle size calibration has been performed using aerodynamic time-of-flight techniques. Mass spectra of several hundred ambient particles with aerodynamic diameters of 0.8 μm have been evaluated for statistical classification (Principal Components Analysis [PCA]) in order to identify main chemical components of the prominent particle classes.     

Direct sequencing of neuropeptides in biological tissue by MALDI-PSD mass spectrometry

Dissected tissue pieces of the pituitary pars intermedia from the amphibian Xenopus laevis was directly subjected to matrix-assisted laser desorption/ionization (MALDI) mass analysis. The obtained MALDI peptide profile revealed both previously known and unexpected processing products of the proopiomelanocortin gene. Mass spectrometric peptide sequencing of a few of these neuropeptides was performed by employing MALDI combined with postsource decay (PSD) fragment ion mass analysis. The potential of MALDI-PSD for sequence analysis of peptides directly from unfractionated tissue samples was examined for the first time for the known desacetyl-alpha-MSH-NH2 and the presumed vasotocin neuropeptide. In addition, the sequence of an unknown peptide which was present in the pars intermedia tissue sample at mass 1392.7 u was determined. The MALDI-PSD mass spectrum of precursor ion 1392.7 u contained sufficient structural information to uniquely identify the sequence by searching protein sequence databases. The determined amino acid sequence corresponds to the vasotocin peptide with a C-terminal extension of Gly-Lys-Arg ("vasotocinyl-GKR"), indicating incomplete processing of the vasotocin precursor protein in the pituitary pars intermediate of X. laevis. Both vasotocin and vasotocinyl-GKR are nonlinear peptides containing a disulfide (S-S) bridge between two cysteine residues. Interpretation of the spectra of these two peptides reveals three different forms of characteristic fragment ions of the cysteine side chain: peptide-CH2-SH (regular mass of Cys-containing fragment ions), peptide-CH2-S-SH (regular mass + 32 u) and peptide = CH2 (regular mass -34 u) due to cleavage on either side of the sulfur atoms.     

Integrated planning of acquisition,disassembly and bulk recycling: a case study on electronic scrap recovery

Abstract. Due to national and supranational legislation activities, the recovery of discarded products will attain an increasing momentum. Electronic equipment consists of many different parts and materials. Therefore, the related recovery process is often divided into disassembly to remove harmful substances or reusable parts and into bulk recycling to recover ferrous and non-ferrous metals. In order to consider the interactions between choice of scrap to be recovered (acquisition problem), disassembly and bulk recycling, a mixed-integer linear programming model for integrated planning of these stages is presented in this case study. It is applied to determine the daily allocation of products to processes for a major electronic scrap recovery centre that faces limited processing capacities and market restrictions. The optimization calculations covering typical discarded electronic products to be recycled in the related centre lead to a relevant improvement of the economic success. RID="*" ID="*" The authors would like to thank the German “Bundesministerium für Bildung und Forschung” (Federal Ministry of Education and Research) for supporting the research project “Substance Flow Oriented Closed Loop Supply Chain Management in the Electrical and Electronic Equipment Industry (STREAM)rdquo;. Correspondence to: T. Spengler