Genome-wide multi-parametric analysis of H2AX or γH2AX distributions during ionizing radiation-induced DNA damage response

Background: After induction of DNA double strand breaks (DSBs), the DNA damage response (DDR) is activated. One of the earliest events in DDR is the phosphorylation of serine 139 on the histone variant H2AX (gH2AX) catalyzed by phosphatidylinositol 3-kinases-related kinases. Despite being extensively studied, H2AX distribution[1] across the genome and gH2AX spreading around DSBs sites[2] in the context of different chromatin compaction states or transcription are yet to be fully elucidated. Materials and methods: gH2AX was induced in human hepatocellular carcinoma cells (HepG2) by exposure to 10 Gy X-rays (250 kV, 16 mA). Samples were incubated 0.5, 3 or 24 hours post irradiation to investigate early, intermediate and late stages of DDR, respectively. Chromatin immunoprecipitation was performed to select H2AX, H3 and gH2AX-enriched chromatin fractions. Chromatin-associated DNA was then sequenced by Illumina ChIP-Seq platform. HepG2 gene expression and histone modification (H3K36me3, H3K9me3) ChIP-Seq profiles were retrieved from Gene Expression Omnibus (accession numbers GSE30240 and GSE26386, respectively). Results: First, we combined G/C usage, gene content, gene expression or histone modification profiles (H3K36me3, H3K9me3) to define genomic compartments characterized by different chromatin compaction states or transcriptional activity. Next, we investigated H3, H2AX and gH2AX distributions in such defined compartments before and after exposure to ionizing radiation (IR) to study DNA repair kinetics during DDR. Our sequencing results indicate that H2AX distribution followed H3 occupancy and, thus, the nucleosome pattern. The highest H2AX and H3 enrichment was observed in transcriptionally active compartments (euchromatin) while the lowest was found in low G/C and gene-poor compartments (heterochromatin). Under physiological conditions, the body of highly and moderately transcribed genes was devoid of gH2AX, despite presenting high H2AX levels. gH2AX accumulation was observed in 5’ or 3’ flanking regions, instead. The same genes showed a prompt gH2AX accumulation during the early stage of DDR which then decreased over time as DDR proceeded. Finally, during the late stage of DDR the residual gH2AX signal was entirely retained in heterochromatic compartments. At this stage, euchromatic compartments were completely devoid of gH2AX despite presenting high levels of non-phosphorylated H2AX. Conclusions: We show that gH2AX distribution ultimately depends on H2AX occupancy, the latter following H3 occupancy and, thus, nucleosome pattern. Both H2AX and H3 levels were higher in actively transcribed compartments. However, gH2AX levels were remarkably low over the body of actively transcribed genes suggesting that transcription levels antagonize gH2AX spreading. Moreover, repair processes did not take place uniformly across the genome; rather, DNA repair was affected by genomic location and transcriptional activity. We propose that higher H2AX density in euchromaticcompartments results in high relative gH2AXconcentration soon after the activation of DDR, thus favoring the recruitment of the DNA repair machinery to those compartments. When the damage is repaired and gH2AX is removed, its residual fraction is retained in the heterochromatic compartments which are then targeted and repaired at later times

Trench width dependant deeply etched surface-defined InP gratings for low-cost high speed DFB/DBR

In this paper we are reporting a fabrication process for multi-section telecom lasers based on surface defined lateral gratings, which is compatible with low-cost high-throughput nano-imprint lithography. A new grating definition process is developed, which allow a better control of the cross section geometry to obtain higher coupling strength

Continuous Variable Quantum Key Distribution: Finite-Key Analysis of Composable Security against Coherent Attacks

We provide a security analysis for continuous variable quantum key distribution protocols based on the transmission of squeezed vacuum states measured via homodyne detection. We employ a version of the entropic uncertainty relation for smooth entropies to give a lower bound on the number of secret bits which can be extracted from a finite number of runs of the protocol. This bound is valid under general coherent attacks, and gives rise to keys which are composably secure. For comparison, we also give a lower bound valid under the assumption of collective attacks. For both scenarios, we find positive key rates using experimental parameters reachable today.Comment: v2: new author, technical inaccuracy corrected, new plots, v3: substantially improved key rates against coherent attacks (due to correction of an error in the numerical computation

Economic efficiency of mobile latent heat storages

In a pilot project an optimized mobile latent heat storage based on a system available on the market has been tested at Fraunhofer Institute for Environmental, Safety and Energy Technology. Initially trials were conducted with the aim of optimizing the process of charging and discharging. A specifically constructed test rig at the incineration trials centre at the institute allowed charging and discharging procedures of the mobile latent heat storage with adjustable parameters. In addition an evaluation model was constructed to further optimize the heat exchanger systems. In conclusion the prototype of the mobile latent heat storage was tested in practical operation. The economic and technical feasibility of heat transportation was shown if not utilized waste heat is available

A Methodology for Sustainability Assessment and Decision Support for Sustainable Handling Systems

Sustainable manufacturing is an important goal to reduce the carbon footprint and securing the economic success of companies. To reach sustainable manufacturing it is also necessary to use sustainable equipment. For this purpose, the sustainability indicators of the asset during its whole life cycle need to be considered for decision making during the design and selection of equipment. Missing analysis methods as well as missing awareness of the importance are obstacles in decision making. Therefore, a multi-criterial analysis method for handling systems for decision empowerment is presented in this paper. The presented methodology enables the engineer to analyze the suppliers for decision making in the purchasing process as well as the identification of weak points regarding sustainability in the handling systems. The methodology offers the possibility of analyzing a system of several parts as a whole, rather than just individual parts. The methodology is implemented in a usable software prototype which has a graphical interface for the data input and can be connected to conventional databases. The usability of the tool is shown with a handling system consisting of an industrial robot and a gripping system

Nanolesions induced by heavy ions in human tissues: experimental and theoretical studies

The biological effects of energetic heavy ions are attracting increasing interest for their applications in cancer therapy and protection against space radiation. The cascade of events leading to cell death or late effects starts from stochastic energy deposition on the nanometer scale and the corresponding lesions in biological molecules, primarily DNA. We have developed experimental techniques to visualize DNA nanolesions induced by heavy ions. Nanolesions appear in cells as “streaks” which can be visualized by using different DNA repair markers. We have studied the kinetics of repair of these “streaks” also with respect to the chromatin conformation. Initial steps in the modeling of the energy deposition patterns at the micrometer and nanometer scale were made with MCHIT and TRAX models, respectively

Moderate hypoxia influences excitability and blocks dendrotoxin sensitive K(+ )currents in rat primary sensory neurones

Hypoxia alters neuronal function and can lead to neuronal injury or death especially in the central nervous system. But little is known about the effects of hypoxia in neurones of the peripheral nervous system (PNS), which survive longer hypoxic periods. Additionally, people have experienced unpleasant sensations during ischemia which are dedicated to changes in conduction properties or changes in excitability in the PNS. However, the underlying ionic conductances in dorsal root ganglion (DRG) neurones have not been investigated in detail. Therefore we investigated the influence of moderate hypoxia (27.0 ± 1.5 mmHg) on action potentials, excitability and ionic conductances of small neurones in a slice preparation of DRGs of young rats. The neurones responded within a few minutes non-uniformly to moderate hypoxia: changes of excitability could be assigned to decreased outward currents in most of the neurones (77%) whereas a smaller group (23%) displayed increased outward currents in Ringer solution. We were able to attribute most of the reduction in outward-current to a voltage-gated K(+ )current which activated at potentials positive to -50 mV and was sensitive to 50 nM α-dendrotoxin (DTX). Other toxins that inhibit subtypes of voltage gated K(+ )channels, such as margatoxin (MgTX), dendrotoxin-K (DTX-K), r-tityustoxin Kα (TsTX-K) and r-agitoxin (AgTX-2) failed to prevent the hypoxia induced reduction. Therefore we could not assign the hypoxia sensitive K(+ )current to one homomeric K(V )channel type in sensory neurones. Functionally this K(+ )current blockade might underlie the increased action potential (AP) duration in these neurones. Altogether these results, might explain the functional impairment of peripheral neurones under moderate hypoxia

Kollaborative Datenpraxis in der Bildungsgeschichte. Wie das Schularchive-Wiki die bildungshistorische Forschung unterstützt

Im Mittelpunkt des Beitrags steht das Schularchive-Wiki, mit dem Wissensbestände aus lokalen Schularchiven erschlossen und dokumentiert werden können. Es ermöglicht und fördert kollaboratives Arbeiten zur deutschen Schulgeschichte und stellt dabei eine Form von citizen science dar. (DIPF/Orig.

Information retrieval systems in education

В работе рассматриваются основные принципы построения информационно‐поисковых систем (ИПС) и их практического применения в образовательном процессе. Рассматриваются различные методики обучения пользователей технологии поиска информации, так как уровень компетентности в области информационного поиска у школьников и студентов остается низким. Приводятся понятия и определения, обсуждаются информационные потребности пользователей. Рассматривается представление информации в ИПС, принципы анализа текстов и индексирования документов, типичные модели и алгоритмы поиска информации. Приводятся основные сведения о классификации документов. Обсуждаются современные словарные, классификационные и метапоисковые ИПС, их практическое применение и критерии эффективности