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.     

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.     

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.     

High-Temperature Electrical Properties in the ThO2-Rich Region of ThO2-RE2O3 Systems

In the present study the n -type electronic conduction in terms of the parameter p e, and the phase relations in several ThO₂-RE2O₃ systems were examined. Large fluorite solid solution regions exist at elevated temperatures. It was demonstrated that RE₂O₃-doped thoria compositions feature lower parameters p e, and higher chemical stability than the conventional stabilized ZrO2 electrolytes. The results are given in terms of the characteristic parameter p e, in the temperature range from 1000° to 1600°C. The experimental investigations were made using a new thermodynamic measuring system.     

Enabling customers engagement and collaboration for small and medium-sized enterprises in ubiquitous multi-channel ecosystems

Over the last few years, we have encountered an exponential growth in online communication opportunities. Organizations have more and more ways to connect and engage with their current or future customers. The existence of more opportunities in connecting to people can be both an enabler and a burden. Being present at a multitude of different channels requires the effective management of a very large number of adapted contents, formats, and interaction patterns fulfilling the communication and cooperation needs of distributed target groups. In this respect, we integrate existing fragmented communication and monitoring approaches into a full-fledged communication model as a basis for an adequate engagement approach. We describe applications of our approach in both the eTourism and manufacturing domain. In this paper, we introduce an approach that will enable communication, collaboration and value exchange of users through a multitude of online interaction possibilities based on the use of semantic technology. Finally, we also compare our approach with existing solutions with respect to the identified challenges in this subject.     

On‐the‐fly generation and rendering of infinite cities on the GPU

In this paper, we present a new approach for shape‐grammar‐based generation and rendering of huge cities in real‐time on the graphics processing unit (GPU). Traditional approaches rely on evaluating a shape grammar and storing the geometry produced as a preprocessing step. During rendering, the pregenerated data is then streamed to the GPU. By interweaving generation and rendering, we overcome the problems and limitations of streaming pregenerated data. Using our methods of visibility pruning and adaptive level of detail, we are able to dynamically generate only the geometry needed to render the current view in real‐time directly on the GPU. We also present a robust and efficient way to dynamically update a scene's derivation tree and geometry, enabling us to exploit frame‐to‐frame coherence. Our combined generation and rendering is significantly faster than all previous work. For detailed scenes, we are capable of generating geometry more rapidly than even just copying pregenerated data from main memory, enabling us to render cities with thousands of buildings at up to 100 frames per second, even with the camera moving at supersonic speed.     

A simple method for the objective characterisation of fabric softness. Part 1: Influence of bleaching,dyeing and crosslinking of wool*

A simple method for the characterisation of fabric softness using a conventional tensile tester and a special measurement device has been developed. The method is demonstrated to be especially useful in detecting changes in softness of a given substrate due to different treatments. The results obtained, particularly hysteresis at 75% of the maximum extension, provide a good correlation with subjective ranking for samples that are subjectively distinguishable; they also differentiate well between samples which seem subjectively indistinguishable. Screening tests were carried out, mainly on wool fabrics, to find the effect of different treatments such as oxidative (alkaline and acidic) and reductive (Blankit IN) bleaching, dyeing with acid and a 1:2 metal complex, chrome and (mono and bi)reactive dyes, the effect of the antisetting agent Basolan AS (BASF) and of crosslinking with Irgasol HTW (CGY) on fabric softness.     

The determination of molecular weights of polymers from critical concentrations of ternary systems polymer-polymer-solvent

The dependence of the critical concentration of the ternary system polymer-polymer-solvent on the molecular weight can be expressed by the relation where c_c is the critical concentration, M? the appropriate average of the molecular weight of both polymers; A and c_c∞ are constants for the given system. The possibility of determining the molecular weight of one of the polymers from the value c_c and the molecular weight of the known polymer with the aid of equation (1) is discussed.     

The Kinetics of the Thermal Decomposition of Thermoplastic Polyurethane Elastomers under Thermoplastic Processing Conditions

A theoretical approach to the kinetics of the thermal decomposition of molten thermoplastic polyurethane elastomers, under conditions of thermoplastic processing, is described. On the basis of these considerations, the thermal decomposition in different instruments (melt index analyser and measuring extruder) can be described quantitatively and the various results can be compared. As a result, identical conditions of decomposition of the melt can be defined accurately, thus opening up the possibility of combining experimental values from different instruments. The fundamental kinetic equation obtained for the kinetics of the thermal decomposition of thermoplastic polyurethanes describes the decomposition reaction and the reverse reaction (formation reaction) – which is dependent on the system of measurement and processing – as a function of the molar mass (end‐group concentration) of the original product, determined from the velocity constants for the decomposition reaction and back reaction. The consideration of the limiting value for t → ∞ is in agreement with the equilibrium constant. Consequently, the development of physical characteristic functions of thermoplastic polyurethane elastomers – independent of the system of measurement – is possible.

Experimental values and calculated curves for the thermal decomposition of PUR‐Et in a melt index analyser.