Elucidation of the Clustered Nano-Architecture of Radiation-Induced DNA Damage Sites and Surrounding Chromatin in Cancer Cells: A Single Molecule Localization Microscopy Approach

In cancer therapy, the application of (fractionated) harsh radiation treatment is state of the art for many types of tumors. However, ionizing radiation is a “double-edged sword”—it can kill the tumor but can also promote the selection of radioresistant tumor cell clones or even initiate carcinogenesis in the normal irradiated tissue. Individualized radiotherapy would reduce these risks and boost the treatment, but its development requires a deep understanding of DNA damage and repair processes and the corresponding control mechanisms. DNA double strand breaks (DSBs) and their repair play a critical role in the cellular response to radiation. In previous years, it has become apparent that, beyond genetic and epigenetic determinants, the structural aspects of damaged chromatin (i.e., not only of DSBs themselves but also of the whole damage-surrounding chromatin domains) form another layer of complex DSB regulation. In the present article, we summarize the application of super-resolution single molecule localization microscopy (SMLM) for investigations of these structural aspects with emphasis on the relationship between the nano-architecture of radiation-induced repair foci (IRIFs), represented here by γH2AX foci, and their chromatin environment. Using irradiated HeLa cell cultures as an example, we show repair-dependent rearrangements of damaged chromatin and analyze the architecture of γH2AX repair clusters according to topological similarities. Although HeLa cells are known to have highly aberrant genomes, the topological similarity of γH2AX was high, indicating a functional, presumptively genome type-independent relevance of structural aspects in DSB repair. Remarkably, nano-scaled chromatin rearrangements during repair depended both on the chromatin domain type and the treatment. Based on these results, we demonstrate how the nano-architecture and topology of IRIFs and chromatin can be determined, point to the methodological relevance of SMLM, and discuss the consequences of the observed phenomena for the DSB repair network regulation or, for instance, radiation treatment outcomes.     

CORDIS无机粘结剂的特性与试验

介绍了德国HA公司最新研制的CORDIS无机粘结剂的组成与性能以及应用中的问题。     

On the role of hydrophilicity and hydrophobicity in aqueous heterophase polymerization

This paper reports on experimental results of aqueous heterophase polymerizations with monomers of quite different solubility in water ranging from the water-soluble 2-hydroxyethyl methacrylate to lauryl methacrylate with solubility in water of only about 10⁻⁴ mM. A calorimetric study revealed the strong influence of both the hydrophilicity of the monomer and the stirrer speed on the rate of polymerization in the absence of surfactants. In order to obtain maximum latex yield and high efficiency (which is a measure considering colloidal properties, polymerization recipe, and polymerization parameters) the initiator-surfactant combination must be properly chosen in dependence on the hydrophilicity of the monomer. Results are presented for sodium alkyl sulfates or disodium-N-stearoyl-l-glutamate as surfactant and potassium peroxodisulfate, or poly(ethylene glycol)-azo- compounds, or 2,2′-azobis(N-2′-methylpropanoyl-2-amino-alkyl-1)-sulfonates as initiators.     

An ionene with spirane structure (spiroionene)

The secondary diamine 1,3,5,7-tetrahydro[1,2c:4,5c'] benzodipyrrole (3) and 1,2,4,5-tetrabromomethylbenzene (1) form a polymeric ionene with spirane structure through a repetitive alkylation reaction. The structure of the product could be proven by¹³C-NMR spectroscopy by comparison with suitable reference compounds. Solutions in aqueous methanol exhibit a typical polyelectrolyte effect. Variation of the counterions produces sufficient solubility in organic solvents. From the crystal structure of a similar model compound one can conclude that the synthesized polymer has a rod-like shape.     

Five-year experience with setup and implementation of an integrated database system for clinical documentation and research

In radiation oncology, where treatment concepts are elaborated in interdisciplinary collaborations, handling distributed, large heterogeneous amounts of data efficiently is very important, yet challenging, for an optimal treatment of the patient as well as for research itself. This becomes a strong focus, as we step into the era of modern personalized medicine, relying on various quantitative data information, thus involving the active contribution of multiple medical specialties. Hence, combining patient data from all involved information systems is inevitable for analyses. Therefore, we introduced a documentation and data management system integrated in the clinical environment for electronic data capture. We discuss our concept and five-year experience of a precise electronic documentation system, with special focus on the challenges we encountered. We specify how such a system can be designed and implemented to plan, tailor and conduct (multicenter) clinical trials, ultimately reaching the best clinical performance, and enhancing interdisciplinary and clinical research.     

Aqueous heterophase polymerization of styrene—a study by means of multi-angle laser light scattering

An online multi-angle laser light scattering study of ab initio surfactant-free styrene emulsion polymerization reveals unexpected results regarding the development of the dispersity during the whole reaction starting from mixing styrene and water at reaction temperature. The experimentally observed change in the dispersity, which is an indirect measure of the average characteristic size of the colloidal objects, allows the identification of three characteristic intervals. During interval A the equilibration of styrene in water is characterized by the formation of styrene domains, which increase in number and size until an equilibrium state is reached. This means that there is virtually no homogeneous/molecular styrene in water solution but rather nanodroplets of about 200 nm in diameter (assuming spherical shape) are formed. During interval B, after initiation of the polymerization and particle formation, the dispersity increases again as the average size decreases and the number of scattering objects increases. The polymer particles suck up the monomer from the monomer nanodroplets, which leads to the disappearance of the nanodroplets and to a decrease in the average size. During interval C the average size increases again due to the predominantly growth of the polystyrene particles.     

The participation of soluble factors in the ω-oxidation of fatty acids in the liver of the sheep

The removal of soluble components from an ovine hepatic microsomal preparation decreased the ω-hydroxylation of dodecanoic and hexadecanoic acids. The results suggest that one or more soluble components play a role in the microsomal ω-hydroxylation of fatty acids. The possible roles in the reaction of catalase (known to stimulate the microsomal desaturations of fatty acids and alkylglycerols) and superoxide dismutase were investigated. The addition of these enzymes to the complete (but not the washed) microsomal preparation stimulated both the initial ω-hydroxylation reaction and the subsequent dehydrogenation reactions of the ω-oxidation pathway. The similarity of the effects of catalase and superoxide dismutase and stimulation of two different steps of the ω-oxidation pathway suggest that these agents are acting indirectly by removing active oxygen species rather than directly on the enzymes of microsomal fatty acid ω-hydroxylation.     

Zur kinetik der acrylnitril-polymerisation

The heterogeneous bulk polymerization of acrylonitrile initiated by AIBN has been studied by means of an improved dilatometric technique and a new method of analysis, where the initial reaction rate (v_w)₀ results from the intercept of a straight line in a \documentclass{article}\pagestyle{empty}\begin{document}$ \frac {\ln \left( 1 \hbox{---} {\rm U} \right)} {{\rm e}^{{- 0,5} {\rm k}_{\rm s}{\rm t} \hbox{---} 1}}$\end{document} versus t plot. It has been found that the initial reaction rate is proportional to the square root of the initial catalyst concentration S₀. The ratio of the rate coefficients of propagation and termination\documentclass{article}\pagestyle{empty}\begin{document}$\frac { {\rm k}_{\rm a} } { {\rm k}_{ {\rm w}^{2} } } $\end{document} could be calculated from the slope of a straight line passing through the origin in a plot of (v_w)₀ versus \documentclass{article}\pagestyle{empty}\begin{document}$\sqrt { {\rm S}_{0} }$\end{document} and yielded a value of 280 mol 1^?1.     

Untersuchung des einflusses molekularer parameter auf morphologie und eigenschaften von polyethylenen niedriger dichte

Based on the example of PE-LD grades and on model substances obtained by preparative fractionation (fractions in the molecular weight range M?_w = 1.2 ? 390·10⁴ g/mol), comprehensive investigations regarding the problems of structure/properties have been carried out. The correlations of M?_w with 15 physical and application technological perameters have been investigated taking into account the reaction mechanism during the manufacturing of PE-LD in the tubular and agitated autoclave reactor, resulting in the formation of so-called primary structure perameters M?_n, M?_w, molar mass distribution, short chain branching and long chain branching. For the interpretation of the results, among other factors, also the morphological conditions have been taken into consideration, which in connection with the molecular parameters reveal — for specific M?_w-ranges — strong changes and saturation ranges, resp., for the physical and application technological properties.