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The chronic infection hypothesis for novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant emergence is increasingly gaining credence following the appearance of Omicron. Here, we investigate intrahost evolution and genetic diversity of lineage B.1.517 during a SARS-CoV-2 chronic infection lasting for 471 days (and still ongoing) with consistently recovered infectious virus and high viral genome copies. During the infection, we find an accelerated virus evolutionary rate translating to 35 nucleotide substitutions per year, approximately 2-fold higher than the global SARS-CoV-2 evolutionary rate. This intrahost evolution results in the emergence and persistence of at least three genetically distinct genotypes, suggesting the establishment of spatially structured viral populations continually reseeding different genotypes into the nasopharynx. Finally, we track the temporal dynamics of genetic diversity to identify advantageous mutations and highlight hallmark changes for chronic infection. Our findings demonstrate that untreated chronic infections accelerate SARS-CoV-2 evolution, providing an opportunity for the emergence of genetically divergent variants.

The experience of anxiety is central to the development of chronic pain. Music listening has been previously shown to exert analgesic effects. Here we tested if an active engagement in music making is more beneficial than music listening in terms of anxiety and pain levels during physical activity that is often avoided in patients with chronic pain. We applied a music feedback paradigm that combines music making and sports exercise, and which has been previously shown to enhance mood. We explored this method as an intervention to potentially reduce anxiety in a group of patients with chronic pain (N = 24, 20 female and 4 men; age range 34–64, M = 51.67, SD = 6.84) and with various anxiety levels. All participants performed two conditions: one condition, Jymmin, where exercise equipment was modified with music feedback so that it could be played like musical instruments by groups of three. Second, a conventional workout condition where groups of three performed exercise on the same devices but where they listened to the same type of music passively. Participants' levels of anxiety, mood, pain and self-efficacy were assessed with standardized psychological questionnaires before the experiment and after each condition. Results demonstrate that exercise with musical feedback reduced anxiety values in patients with chronic pain significantly as compared to conventional workout with passive music listening. There were no significant overall changes in pain, but patients with greater anxiety levels compared to those with moderate anxiety levels were observed to potentially benefit more from the music feedback intervention in terms of alleviation of pain. Furthermore, it was observed that patients during Jymmin more strongly perceived motivation through others. The observed diminishing effects of Jymmin on anxiety have a high clinical relevance, and in a longer term the therapeutic application could help to break the Anxiety Loop of Pain, reducing chronic pain. The intervention method, however, also has immediate benefits to chronic pain rehabilitation, increasing the motivation to work out, and facilitating social bonding.

Optical engineering 61(09), 095103 (2022). doi:10.1117/1.OE.61.9.095103, Published by SPIE, Bellingham, Wash.

While previous research has conclusively established that children with higher cognitive ability and those originating from advantaged socioeconomic status (SES) backgrounds have better educational outcomes, the interplay between the influences of cognitive ability and social origin has been largely overlooked. The influence of cognitive ability might be weaker in high-SES families as a result of resource compensation, and stronger in high-SES families owing to resource multiplication. We investigate these mechanisms while taking into account the possibility that the association between cognitive ability and educational attainment might be partly spurious due to unobserved genetic and environmental influences. We do so by analysing a large sample of twins from the German TwinLife study (Npairs = 2,190). Our results show that the association between cognitive ability and educational attainment is to a large extent confounded by genetic and shared environmental factors. If this is not considered, and this is the case in most previous studies, high-SES parents seem to compensate for the lower cognitive ability of their children. However, when we consider the genetic and shared environmental confounding, the resource compensation effect becomes non-significant.

Additional file 10: Figure S7. Cellular back mapping identifies co-localizing protein populations at extranuclear DNA segments. A. images shown in Fig. 4, all channels. B. Analysis of KDM6A TPR and NPM1: Cellular back mapping identifies a colocalizing population (orange) and free KDM6A TPR (green) and NPM1 (red) at cytoplasmic DNA segments. C. scatterplot analysis and cellular back mapping of KDM6A variants and DAPI as indicator of KDM6A-DNA complexes. In KDM6A WT scatterplot we identified four populations: 1 = cytoplasmic KDM6A (without DAPI) and 4 = DAPI (without KDM6A), as well as, populations #2 and #3, which resemble different ratios of KDM6A-DNA complexes. Population 2 is located at the lamina and in nucleolar puncta, and population 3 is located within the nucleoplasm. Substitution variant T726K shows minor differences in populations #2 and #4, as the lamina in #2 is less clearly visible, but strongly enriched in population #4. Contour scatterplot of JmjC or TPR with DAPI identified only three populations, with population #1 being absent. Back mapping clearly indicates compartment-wise localization of different DAPI-KDM6A JmjC or TPR compositions.

Additional file 5: Figure S2. Activity assay and data analysis. In this section, we describe our data analysis workflow. A. delta (grey shaded area) in fluorescence emission spectrum of eGFP-KDM6A WT lysate before incubation and after incubation with GFP-trap dynabeads. For data analysis, the amount of pulled fluorescent protein was determined by subtracting the eGFP fluorescence emission (470 nm excitation) after incubation with GFP-trap dynabeads from eGFP fluorescence emission before incubation with eGFP-trap dynabeads. Fluorescence intensities in the range of 500–530 nm were integrated subsequently (later referred to as integrated fluorescence). B. Maximum-normalized spectra obtained from crude cell lysate of eGFP, eGFP-KDM6A WT or eGFP-KDM6A Q1133A samples. All fluorescence emission spectra of the substitution variants had a similar profile between 500 and 530 nm. This was used to compare the amount of protein for each variant. Q1133A variant is shown exemplarily for all other substitution variants. C. Fluorescence emission spectra of WT and ΔJmjC. The high signal of ΔJmjC towards the blue end of the spectrum is due to scatter, which could indicate protein instability under the given (low salt) buffer conditions. D. 1–238 ng demethylated product (H3K27me2 peptide, MW = 2945.5 g/mol) was obtained from at least nine data points from three independent experiments, each in triplicates and fitted with a four parameters logistic regression (4-PL) according to Eq. 1: y = d + a − d 1 + x c b $$ \mathrm{y}=\mathrm{d}+\frac{\mathrm{a}-\mathrm{d}}{1+{\left(\frac{\mathrm{x}}{\mathrm{c}}\right)}^{\mathrm{b}}} $$ (1) with y = assay readout absorption, x = amount of product in A., amount of KDM6A species, either by fluorescence in B. or amount of protein in D., a = background signal, d = maximum signal, b = slope factor, c = c50, x-value at half maximum y.The following fit results were obtained: a = 0.29, b = 1.27, d = 1.73 and c = 62.4 ng. E. The amount of protein was plotted against absorption (shown for KDM6A WT) and fitted accordingly with 4-PL, with c being the only open parameter. c50 for WT was determined with 518,000 +/− 56,000 AU. To correct for background and maximum signal fluctuation between experiments, they were normalized to the values obtained from the product curve fit (a = 0.29, d = 1.73). F. A defined amount of recombinant eGFP (27 kDa) was used to convert the x-axis from fluorescent signal to the amount of protein. The linear dependency was used to calculate the amount of eGFP-KDM6A (181 kDa) per fluorescent unit. The molar integrated fluorescence (500–530 nm) from emission spectra for recombinant eGFP (MW = 26.9 kDa) was determined as 2.34E+ 18 AU/mol from the relation 1 ng eGFP = 86,900 [AU]. Therefore, 1 ng eGFP-KDM6A WT would yield an integrated fluorescence signal of 1.29E+ 03 AU. G. Data from E. and F. were used to transform the x-Axis with the fluorescent signal into the amount of KDM6A protein,. Approximated from D., the respective c50 always corresponded to 62.4 product. This correlation was used to calculate the specific activity for each variant. Given the fixed time of 240 min per assay, the specific activity under these conditions was calculated. The c50 for all available substitution variants was obtained in the same manner, fixing all parameters except c, using it as a relative measure of activity. At least four independent triplicate measurements were obtained for each substitution variant. H. absorption for truncated variants, three repeats with triplicates each. Since the truncated variants showed an unusual spectrum with a high scatter fraction at lower wavelengths (see C.), a quantification was impossible. Therefore, we qualitatively confirmed, that all truncated variants with a JmjC domain are catalytically active (green boxes) and those without JmjC domain are catalytically dead (red boxes). The distribution of the signal over the background is an evidence for activity in all truncated variants with a JmjC domain. ΔJmjC and TPR do not exceed assay background levels (zero), while WT, ΔIDR, ΔTPR and JmjC are all above background. I. Activity of T726K is dependent on post-expression time. WT activity does not change significantly between 24 h (black) to 48 h (grey), whereas in T726K activity is slightly lower than WT after 24 h (blue) and strongly reduced after 48 h (cyan) when comparing c50-values.

Additional file 4: Figure S1. Bioinformatic analysis of KDM6A tetratricopeptide repeats. A. Alignment of annotated KDM6A TPRs using the TPRprediction and alignment tool published in [37]. All annotated KDM6A TPRs with the given amino acid range (see label) were compared for their TPR conservation to the consensus sequence as published in [38] with the most conserved amino acids W4, L7, G8, Y11, A20, Y24, A27 and P30. Identity and p-values are shown on the right site. The TPR motif could not be identified for TPR3 (aa 170–199). Color coding according to CLUSTAL W alignment. B. Secondary structure prediction of TPR3 using the Quick2D on the MPI Bioinformatics toolkit server [39, 40] indicated a high probability for aa 14–26 to form an α-helix, but aa 1–10 tend to form either an α-helix or a β-strand. Of note, the canonical aa 34 TPR repeating unit forms a helix-turn-helix motif [38]. In general, the N-terminal TPRs 1–4 show less strict conservation towards the canonical TPR sequence compared to the C-terminal TPRs 6–8.

Additional file 1: Table S1. Predicted solubility and pI of KDM6A substitution and truncation variants. Predicted solubility and pI of KDM6A substitution and truncation variants using Protein-Sol from the University of Manchester based on published sequences [35, 36]. Compared to KDM6A WT protein TPR and ΔIDR show reduced solubility, whereas the IDR sequence alone is predicted to be most soluble. Single substitution do not affect pI and solubility, as expected. Among nuclear proteins, such as components of the COMPASS complex (KMT2C/D, WDR5, RBBP5) and NPM1, KDM6A is the least soluble. Protein identifier were taken from UniProt.

Additional file 3: Table S3. P-Values and scoring results from Figs. 5 and 6. A. P-Values from Fig. 5. B. Scoring results used in Fig. 5. C. P-Values from Fig. 6.

Additional file 9: Figure S6. Pathway enrichment analysis of MS data from KDM6A-tagGFP2 cell lines. A. Data from quadruplicates of three independent experiments of two different KDM6A-tagGFP2 cell lines using the reactome database. MS data sets were applied to the reactome analysis database. The resulting output shows significantly enriched pathways. The five most interesting pathways are depicted: cell cycle, chromatin organization, DNA repair, RNA metabolism including rRNA processing and protein metabolism including ribosome biogenesis and post-translational modification of histones. B. Top ten proteins identified by MS in KDM6A-tagGFP2 stable cell lines VM-CUB1 and RT-112. Among the top ten proteins in KDM6A pull down and subsequent MS, Nucleophosmin (NPM1), Nucleolin, ribosomal subunits 40S and 60S, as well as histone variants, are detectable. Mutational KDM6A and KMT2C/D status and experiments with RT-112 and VM-CUB1 have been recently published [18].

Additional file 8: Figure S5. Western Blot control experiments and raw blots. A. eGFP-KDM6A TPR whole cell lysate and the corresponding IP fraction was separated on a Western Blot and stained with eGFP (CST) or RBBP5 (CST) antibodies. RBBP5 precipitated with eGFP-KDM6A TPR. B. Dynabeads washing control on same membrane, washed with 3x RIPA like buffer (RLB). While KDM6A WT pulls a clearly visible RBBP5 band and a low WDR5 band, both are undetectable in eGFP-transfected cells alone (negative control). C. Raw blots from Fig. 3. Lysate and Co-IP for selected KDM6A variants and eGFP. IP and corresponding lysate lanes were also on the same blot. All experimental conditions for the blots presented were kept constant. D. Raw blots from Fig. 1B/D. Protein lanes shown in main figures are in red boxes. The PageRuler Plus Prestained protein ladder (Thermo Fisher) was used for orientation.

Additional file 11: Figure S8. Distribution and expression levels of p-γH2A.X and RAD51 after KDM6A overexpression and endogenous localization of KDM6A during mitosis. A. p-γH2A.x protein level in untransfected and KDM6A variants transfected T-24 cells. Note, that even in strongly overexpressed KDM6A WT cells, p-γH2A.X was not increased, but strongly so in KDM6A JmjC and ΔTPR cells. B. Endogenous localization of KDM6A (CST antibody, 2nd antibody goat-anti-rabbit AbStar red) as imaged with Leica STED SP8 in HBLAK cells. For STED, the sample was depleted with 35% of 775 nm laser. C. RAD51 proteins were detected at a persisting chromatin bridge of two daughter cells, with cell 1 being KDM6A ΔTPR positive. Image was taken with Abberior STED, excitation laser 640 nm 5% and depletion laser 775 nm with 40%.

Additional file 2: Table S2. Primer, antibodies and peptides used in this study. A. Primer used for site-directed mutagenesis and amplification. B. Primary and secondary antibodies used in this study. C. H3K27-peptides used in this study.

Additional file 6: Figure S3. Control experiments for antibody staining specificity and endogenous KDM6A protein levels. SW-1710 and T-24 cells were transfected with KDM6A WT or ΔIDR variants and stained with two different antibodies (sc-514,859, Santa Cruz biotechnology and CST-33510, Cell Signaling) raised against epitopes within the KDM6A central region (IDR) and 2nd antibody labeled with AbStar Red (Abberior). Clearly, both antibodies (in red channel) detect transfected KDM6A WT protein (very strong signals in green channel), but not the ΔIDR variant. The untransfected control cells show endogenous KDM6A in both cell lines stained with both KDM6A antibodies.

Additional file 7: Figure S4. Localization study of KDM6A variants in normal and invasive urothelial (cancer) cells. A. KDM6A substitution and deletion variants are localized in the cytoplasm and nucleus in T-24 cells. Substitutions cause mild effects, whereas deletion variants cause stronger cellular responses such as DNA release and mitotic errors. B. Representative KDM6A deletion variants are localized in the cytoplasm and nucleus in HBLAK. Two different phenotypes have been observed: a milder phenotype (majority of cells) and a phenotype (minority of cells) which reproducibly causes stronger cellular responses such as DNA release and mitotic errors. DAPI counterstaining of the nucleus and the respective overlay of both channels (DAPI in blue and GFP in green) is displayed. Images are taken in 2048 × 2048 resolution using a widefield microscope Olympus FX81 with 60x oil objective with post-processing using HuygensPro20.10. Effects of KDM6A variants in SW-1710 cells is shown in Fig. 2.

As people increasingly rely on online media and recommender systems to consume information, engage in debates and form their political opinions, the design goals of online media and news recommenders have wide implications for the political and social processes that take place online and offline. Current recommender systems have been observed to promote personalization and more effective forms of informing, but also to narrow the user’s exposure to diverse content. Concerns about echo-chambers and filter bubbles highlight the importance of design metrics that can successfully strike a balance between accurate recommendations that respond to individual information needs and preferences, while at the same time addressing concerns about missing out important information, context and the broader cultural and political diversity in the news, as well as fairness. A broader, more sophisticated vision of the future of personalized recommenders needs to be formed - a vision that can only be developed as the result of a collaborative effort by different areas of academic research (media studies, computer science, law and legal philosophy, communication science, political philosophy, and democratic theory). The proposed workshop will set first steps to develop such a much needed vision on the role of recommender systems on the democratic role of the media and define the guidelines as well as a manifesto for future research and long-term goals for the emerging topic of fairness, diversity, and personalization in recommender systems., Dagstuhl Reports, Volume 9, Issue 11, pages 117-124

Background: Resilience refers to the capacities and resources an individual uses to overcome personal crises and sickness and to adapt to chronic stressors [ref:1]. No study has investigated its variability and predictive value for return-to-work outcomes in rehabilitation treatment. Aim:[for full text, please go to the a.m. URL], 15th Congress of the European Forum for Research in Rehabilitation (EFRR)

Hintergrund: Das empirische Wissen über die psychischen Belastungen und Auffälligkeiten von Familien mit Migrationshintergrund (MH) ist gering. Die wenigen vorhandenen Studien sprechen für eine etwas stärkere Belastung von Kindern und Jugendlichen mit MH im Vergleich zu solchen ohne MH, wobei dieser Unterschied vermutlich durch ihre schlechteren Lebensbedingungen und den geringeren sozioökonomischen Status bedingt ist. Methode: In einer Längsschnittstudie wurden psychische Auffälligkeiten von Kindern mit und ohne MH verglichen, zunächst im Kindergartenalter und noch einmal 10 Jahre später im Jugendalter. Zusätzlich wurden explorativ Unterschiede zwischen Migranten und Nichtmigranten im Hinblick auf ein im Kindergartenalter durchgeführtes Elterntraining (Triple P) untersucht. Die Daten stammten aus dem längsschnittlich angelegten Projekt «Zukunft Familie III». Die Untersuchungsstichprobe bestand aus 70 Familien mit (19,4%) und 291 Familien ohne MH (80,6%). Das durchschnittliche Alter der Kinder im Kindergartenalter betrug 4,2 Jahre, derjenigen im Jugendalter 14,1 Jahre; 45,7% waren Mädchen. Ergebnisse: Die Unterschiede zwischen den Kindern und Jugendlichen mit und ohne MH waren gering. Sie verringerten sich vom Kindergarten- zum Jugendalter. Bei Jugendlichen mit MH zeigten sich vermehrt Hinweise auf eine Computerspielabhängigkeit, und sie verbrachten mehr Zeit mit Social-Networking. Jugendliche ohne MH wiesen ein größeres Risiko für Essstörungen und riskantes Sexualverhalten auf. Für die Vorhersage von psychischen Auffälligkeiten im Jugendalter spielten weder der MH noch der soziale Status eine Rolle, relevant waren ausschließlich die psychischen Auffälligkeiten im Kindergartenalter. Migranten und Nichtmigranten profitierten gleichermaßen vom angebotenen Elterntraining. Migranten, die eine Teilnahme ablehnten, zeigten im Vergleich zu den Nichtmigranten deutlich ungünstigere Werte. Schlussfolgerungen: Der Heterogenität von Migranten muss in künftigen Studien stärker Rechnung getragen werden. Aufgrund der Zunahme von Familien mit MH in Deutschland sollten vermehrt Anstrengungen unternommen werden, Kinder, Jugendliche und deren Eltern zu untersuchen. Zum besseren Verständnis der Auswirkungen von Migration sind Längsschnittstudien unabdingbar.

Hintergrund: Das empirische Wissen über die psychischen Belastungen und Auffälligkeiten von Familien mit Migrationshintergrund (MH) ist gering. Die wenigen vorhandenen Studien sprechen für eine etwas stärkere Belastung von Kindern und Jugendlichen mit MH im Vergleich zu solchen ohne MH, wobei dieser Unterschied vermutlich durch ihre schlechteren Lebensbedingungen und den geringeren sozioökonomischen Status bedingt ist. Methode: In einer Längsschnittstudie wurden psychische Auffälligkeiten von Kindern mit und ohne MH verglichen, zunächst im Kindergartenalter und noch einmal 10 Jahre später im Jugendalter. Zusätzlich wurden explorativ Unterschiede zwischen Migranten und Nichtmigranten im Hinblick auf ein im Kindergartenalter durchgeführtes Elterntraining (Triple P) untersucht. Die Daten stammten aus dem längsschnittlich angelegten Projekt «Zukunft Familie III». Die Untersuchungsstichprobe bestand aus 70 Familien mit (19,4%) und 291 Familien ohne MH (80,6%). Das durchschnittliche Alter der Kinder im Kindergartenalter betrug 4,2 Jahre, derjenigen im Jugendalter 14,1 Jahre; 45,7% waren Mädchen. Ergebnisse: Die Unterschiede zwischen den Kindern und Jugendlichen mit und ohne MH waren gering. Sie verringerten sich vom Kindergarten- zum Jugendalter. Bei Jugendlichen mit MH zeigten sich vermehrt Hinweise auf eine Computerspielabhängigkeit, und sie verbrachten mehr Zeit mit Social-Networking. Jugendliche ohne MH wiesen ein größeres Risiko für Essstörungen und riskantes Sexualverhalten auf. Für die Vorhersage von psychischen Auffälligkeiten im Jugendalter spielten weder der MH noch der soziale Status eine Rolle, relevant waren ausschließlich die psychischen Auffälligkeiten im Kindergartenalter. Migranten und Nichtmigranten profitierten gleichermaßen vom angebotenen Elterntraining. Migranten, die eine Teilnahme ablehnten, zeigten im Vergleich zu den Nichtmigranten deutlich ungünstigere Werte. Schlussfolgerungen: Der Heterogenität von Migranten muss in künftigen Studien stärker Rechnung getragen werden. Aufgrund der Zunahme von Familien mit MH in Deutschland sollten vermehrt Anstrengungen unternommen werden, Kinder, Jugendliche und deren Eltern zu untersuchen. Zum besseren Verständnis der Auswirkungen von Migration sind Längsschnittstudien unabdingbar.

Irregularities inside the fluid flow in laser fusion cutting of sheet metals cause quality defects like large striation depths or adhered dross. Trim‐cut analysis is used to measure the flow velocities of the molten material by high speed imaging. The so‐called streak analysis creates a repetitive pattern for multiple melt waves and the angle of these patterns is assignable to specific flow velocities. In this article, a discrete fourier transform is used to automatically determine the spatial distribution of flow velocities. The results show that identifying the velocity domains and assigning them to the parameters of the cutting process and quality characteristics is a promising approach to enhance the understanding and to achieve higher quality cuts.

Due to the change in grain size during laser processing in the heat‐affected zone and the solidifying material, the potential of cracking, surface hardening, and decrease in weldability, corrosion resistance and fatigue life may result. It is shown that through combining state‐of‐the‐art temperature simulation of laser processes with thermo‐mechanical volume averaging grain formation simulation, the resulting grain density can be predicted within the order of magnitude found in the two experiments carried out for laser fusion cutting and spot welding of A356. However, fundamental knowledge about the grain density function during rapid solidification, the prediction of the transition from epitactic growth to globular grains and defined validation experiments are needed in order to provide a realistic virtual microstructure.

In laser deep penetration welding, the knowledge on the temperature history of the material is of great interest for the assessment of the quality properties of the weld. For this purpose a hybrid process model that enables the fast calculation of temperature distributions as a function of process parameters is applied. The interaction between laser and material is taken into account by a reduced keyhole model, which exploits a hierarchy in the spatial dimensions occurring at high feed rates. The resulting shape of a stationary keyhole is introduced as a Dirichlet boundary into a thermal finite element simulation in which it is moved through the workpiece according to the process control of the laser beam. The boundary is mathematically described by a level set function and immersed in a fixed computational mesh. The Dirichlet boundary condition is imposed using an embedded boundary method. The calculated temperature distributions are evaluated by means of bead on plate welds conducted in 0.9 mm thick sheets of 1.4301 (AISI 304) stainless steel.

Inclusive transverse momentum spectra of charged particles in photoproduction events in the laboratory pseudorapidity range $-1.2, Comment: 23 pages, latex, 4 figures appended as uuencoded file

European media regulation currently faces several challenges: technology, media and markets have become convergent, while – at the same time – the situations in the individual member states differ in respect of media use, the usage of end devices as well as regulatory aims and frameworks. These challenges can be met with an updated regulatory framework. Core attributes of this updated framework are a reorientation relative to the current framework, a basis in principles, learning aptitude, and a coherent approach to media regulation. This is, however, not just an incremental but a structural change. Other than the regulatory framework currently in place, which takes different types of audiovisual services as a starting point for specific regulation just to follow the same aims, a reoriented regulatory framework could allow for effective regulations that follow specific goals and that address the media landscape as a whole – also taking into account the peculiarities of certain types of media in specific provisions by introducing a general regulation as well as one built upon that. Such a framework is capable of effectively managing a convergent media landscape. An incentive-based opt-in approach would further improve the efficiency of this framework, offering a self-categorisation option for content providers and unburdening regulators while retaining the needed flexibility. Privileging desirable public value services will give incentives for providing such media content across different audiovisual services and form the basis of a vivid and pluralistic media landscape. However, European regulation still has to guarantee a minimum standard. To address the different situations in the member states, they will need some leeway for implementation. This calls for a principle-driven approach, setting coherent regulatory aims and a general framework across Europe, but leaving it to the member states to define requirements for the different content categories for the providers to opt-in to. This will finally lead to a consistent regulatory framework throughout the EU, which is still able to manage the heterogeneity of the different media landscapes. This paper is based on a larger study by the Hans Bredow Institute (HBI) and the Institute for Information Law (IViR).

We experimentally investigated the morphology and mechanism of laser-induced damage in the ablation cutting of thin glass sheets with picosecond pulsed lasers and we compared the experimental results to our models. After several passes of laser ablation, we observed two different kinds of damage morphologies on the cross-section of the cut channel. They are distinguished to be the damage region caused by high-density free-electrons and the heat-affected zone due to the heat accumulation, respectively. Furthermore, micro-cracks can be observed on the top surface of the workpiece near the cut edge. The nano-cracks could be generated by high energy free-electrons but opened and developed to be visible micro-cracks by thermal stress generated in the heat-affected zone. The crack length was proportional to the volume of heat-affected zone. Heat-affected-zone and visible-cracks free conditions of glass cutting were achieved by controlling the repetition rate and spatial overlap of laser pulses.

The study provides an overview of encryption technologies and their impact on human rights. It analyzes in-depth the role of encryption in the media and communications landscape, and the impact on different services, entities and end users. It highlights good practices and examines the legal environment surrounding encryption as well as various case studies of encryption policies. Built on this exploration and analysis, the research provides recommendations on encryption policy that are useful for various stakeholders.

Cor triatriatum was diagnosed in a 32-year-old woman (Case 1) and a 36-year-old man (Case 2). The definitive diagnosis in Case 1 was made by transthoracic 2-D echocardiography, in Case 2 (after a chance finding) only after additional transoesophageal echocardiography. Colour Doppler echo in Case 1 provided information on the number and localization of membrane openings, while in Case 2 simultaneous measurement of maximal flow velocity and normal right-sided pressures indicated that the anomaly was haemodynamically insignificant owing to the size of the central opening in the membrane (maximal diameter 2.1 cm). In Case 1, abnormal haemodynamic findings on right-heart catheterization provided the indication for surgery and the membrane was successfully removed. Postoperatively the patient was much improved and cardiac catheterization demonstrated normal values.

In this article, a dataset from a collaborative nontarget screening trial organised by the NORMAN Association is used to review the state-of-the-art and discuss future perspectives of non-target creening using high-resolution mass spectrometry in water analysis. A total of 18 institutes from 12 European countries analysed an extract of the same water sample collected from the River Danube with either one or both of liquid and gas chromatography coupled with mass spectrometry detection. This article focuses mainly on the use of high resolution screening techniques with target, suspect, and non-target workflows to identify substances in environmental samples. Specific examples are given to emphasise major challenges including isobaric and co-eluting substances, dependence on target and suspect lists, formula assignment, the use of retention information, and the confidence of identification. Approaches andmethods applicable to unit resolution data are also discussed. Although most substances were identified using high resolution data with target and suspect-screening approaches, some participants proposed tentative non-target identifications. This comprehensive dataset revealed that non-target analytical techniques are already substantially harmonised between the participants, but the data processing remains time-consuming. Although the objective of a "fully-automated identification workflow" remains elusive in the short term, important steps in this direction have been taken, exemplified by the growing popularity of suspect screening approaches. Major recommendations to improve non-target screening include better integration and connection of desired features into software packages, the exchange of target and suspect lists, and the contribution ofmore spectra from standard substances into (openly accessible) databases. © Springer-Verlag Berlin Heidelberg 2015.

The study on the future of European audiovsiual media regulation develops new ideas and recommendations for shaping a new European framework. A structural reform is favoured, as a response to digitization and convergence. The new framework should concentrate on general principles and be able to adapt and learn. Regulation should not be linked to types of services, but rather be developed by considering its goals, like protection of minors and consumer protection. Standards should be set allowing for effective regulation and coordination. Moreover by taking a 360-degree view on all relevant areas of regulation, it needs to become visible, where the European Law can offer leeway for to the member states’ own media policy. The study called HERMES draws a precise image of current media consumption and value-added chains by examining several EU member states, as well as certain international states. The developments of the last years are being examined and current phenomena are explored. The centre of attention is the shift away from regular TV to non-linear media and the consumption via alternative channels as well as via new devices, which were not yet taken into account when shaping the present framework. The outcomes are analysed and put into practical guidelines for the near future.

Events with a large rapidity gap in deep inelastic scattering with Q2 greater-than-or-equal-to 10 GeV2 have been studied in the ZEUS detector. The properties of these events with W > 140 GeV are consistent with a leading twist diffractive production mechanism. In the laboratory frame, with E(T)jet greater-than-or-equal-to 4 GeV, 15% of the events are of the 1-jet type with negligible 2-jet production. The single jet is back-to-back in azimuth with the scattered electron. No energy flow is observed between the jet and the proton direction. With a lower jet transverse energy cut 2-jet production is observed both in the laboratory and the gamma*p centre-of-mass systems, demonstrating the presence of hard scattering in the virtual photon proton interactions that give rise to large rapidity gap events.

Rapporto tecnico sulla terza indagine IEA sull'educazione civica e alla cittadinanza Technical report of the third IEA study on civic and citizenship education

Il volume è il rapporto internazionale della terza indagine IEA sull'educazione civica e alla cittadinanza, di cui vengono presntati i risultati, il quadro concettuale di riferimento, gli strumenti di rilevazione utilizzati. Hanno partecipatp all'indagine - promossa dalla International Association for the Evaluation of Educational Achievement) 38 paesi, tra cui l'Italia. La popolazione indagata è costituita dagli studenti al quarto anno di scolarità, per l'Italia gli studenti dell'ultimo anno della scuola secondaria di primo grado. I risultati si riferiscono non soltanto alle conoscenze e alle abilità degli studenti, ma anche ad alcuni atteggiamenti nei confronti di problemi di carattere civico e sociale. Il rapporto discute anche il contributo delle scuole all'educazione alla cittadinanza dei giovani. International report of the third IEA study on civic and citizenship education

Primo rapporto di sintesi dei risultati dello studio comparativo internazionale sull'educazione civica e alla cittadinanza condotto dalla IEA (International Association for the Evaluation of Educational Achievement.

International audience

Das beherrschende Thema der Energiewende ist die künftige Stromerzeugung. Nur wenigen ist bewusst, dass der Endenergieeinsatz für die Wärmeversorgung in Deutschland das 2½-fache des Elektroenergieeinsatzes ausmacht. Nachträgliche Wärmeschutzaktivitäten verlaufen aktuell noch so trage, dass sich voraussichtlich an dieser Relation sobald nichts ändern wird. Es wird zunehmend deutlich, welche Kraftanstrengung damit verbunden wäre, den Wärmeverbrauch des überwiegenden Gebäudebestands um ein Drittel oder sogar auf die Hälfte zu reduzieren. Damit geht die Frage einher: Wie lässt sich die Wärmeversorgung gestalten, wenn fossile Energieträger aus Klimaschutzgründen oder aufgrund der Ressourcenknappheit kaum noch eingesetzt werden dürfen? Der Anteil der erneuerbaren Energien (EE) an der Wärmeversorgung ist jedenfalls aktuell mit 11 % noch denkbar gering. Es hat sich sehr eindeutig ergeben, dass Wärmenetze eine wichtige Basis für die Einbindung der EE auf der Strom- und Wärmeversorgungsseite sind. Besonders hervorzuheben ist, dass sie eine erhebliche Reduzierung des Einsatzes speicherbarer Energieträger ermöglichen, was bei einem Auslaufen des Erdgaseinsatzes von sehr großer Bedeutung sein wird. Da Wärmenetze nur langsam anhand der sich bietenden Gelegenheiten kostenoptimal wachsen können, kommt damit dem Erhalt und laufenden Ausbau der Fernwärmeversorgung eine vorrangige Bedeutung zu. Es muss entsprechend dafür gesorgt werden, dass dem Wärmenetzausbau ohne Unterbrechung förderliche Bedingungen zur Verfügung stehen. Dabei sind auch die wirtschaftlichen Perspektiven der Fernwärmeerzeugung mit einzubeziehen. Der Wärmenetzausbau lässt sich weiterhin unterstützen, indem kommunale Wärmeversorgungspläne systematisch erstellt und in einem gewissen Turnus aktualisiert werden. Ausbaumöglichkeiten würden auf diesem Weg bereits mit einigem zeitlichen Vorlauf erkannt werden. Dieses Instrument hat sich in Dänemark bereits seit Langem bewährt. Weiterhin sollten flexible Betriebsweisen der KWK heutzutage bereits stärker gefördert und Anreize geschaffen werden, damit KWK-Systeme auf die Deckung hoher Anteile der jeweiligen Wärmehöchstlast ausgerichtet werden (hohe Auslegung der KWK). Sowohl die bestehende Förderung des Wärmenetzausbaus als auch die Förderung von Wärmespeicherkapazitäten sollten beibehalten werden. Ein wirtschaftlicher Betrieb von Elektroheizern ist gemäß der Ifam-Studie davon abhängig, dass der hierfür verwendete Strom teilweise von Abgaben und Umlagen befreit wird. Andernfalls kann die hiermit bewirkte Wärmeerzeugung von den Kosten her nicht mit der brennstoffbasierten konkurrieren. Schließlich wird empfohlen, dänischen Erfahrungen folgend den Zugang zum Regelenergiemarkt zur Verbesserung der Erlössituation der KWK und der Elektroheizer stärker zu flexibilisieren.

Ultrafast reflection and secondary ablation have been theoretically investigated with a Fresnel-Drude model in laser processing of transparent dielectrics with picosecond pulsed laser. The time-dependent refractive index has a crucial effect on the cascade ionization rate and, thereby, on the plasma generation. The relative roles of the plasma gas and the incident angle in the reflection are discussed in the case of the oblique incidence. The angular dependence of the reflectivity on the laser-excited surface for s- and p-polarization is significantly different from the usual Fresnel reflectivity curve in the low-fluence limit. A road map to the secondary ablation induced by the reflected pulse is obtained on the angles of the first and second incidence. It indicates that the laser-induced plasma plays a major role in the secondary ablation, which could overcome the saturation of the ablation crater depth or generate microcracks underneath the crater wall.

This thesis studies the process of status attainment during the careers of men and women in the nineteenth and early twentieth centuries and the influence of modernization processes on that process of status attainment. During the decades following World War II, the Western world saw an increasing confidence among the working population and social scientists alike that most people would have occupational careers characterized by upward mobility and by ‘good jobs’. The breeding ground for this idea is commonly dated to the mid- to late nineteenth century, a period characterized by tremendous economic, social and institutional change, including industrialization, mass communication and educational expansion. These modernization processes are expected to have caused changes in status attainment over the course of people’s careers. Across the social spectrum, the population at large is predicted to have had more successful careers. I study the development of occupational status over people’s careers in the period 1865 to 1940. I explain career success by studying the effects of individual characteristics, such as experience and social background, and the influence of regional modernization processes, such as educational expansion and industrialization. Moreover, I assess whether the effects of individual characteristics on career attainment changed over time and according to regional modernization processes. Unlike research focusing on specific occupational groups and localities, this dissertation uses data on the careers of a random sample of the male and female population nationwide. The Historical Sample of the Netherlands (HSN) contains information on the occupational careers of 8,291 men and 4,611 women who were present on the labour market between 1865 and 1940. The HSN is an excellent new database for the longitudinal study of male and female careers, covering the whole of the Netherlands. To include modernization processes at a regional level we have consulted several sources to collect data on regional modernization processes, such as industrialization, educational expansion and mass transport. The sources generally comprise official statistics or registers, and include the annual reviews on educational participation (Verslagen voor het hoger, middelbaar en lager onderwijs) and safety reports on steam engines drawn from the ‘Registers of the Dutch Department for Steam Engineering’. In addition to studying the careers of individuals, I study one of the mechanisms expected to have brought about changes in individual mobility outcomes: the hiring behaviour of employers. According to theories of industrialism, modernization processes caused employers to recruit employees increasingly on the basis of achieved characteristics, such as qualifications and experience, rather than ascribed characteristics, such as religious affiliation and social background. I study ascription- and achievement-based hiring by analysing the requirements stipulated by employers in job advertisements in Dutch newspapers in the period 1870 to 1939. One main conclusion is that individual differences in resources e.g., experience and schooling were clearly important for status attainment of men and women in the nineteenth and early twentieth centuries. Another is that while the classic expectation of increasing career success due to modernization processes was supported, no indication was found that the mechanisms of status attainment changed in response to modernization processes

This thesis studies the process of status attainment during the careers of men and women in the nineteenth and early twentieth centuries and the influence of modernization processes on that process of status attainment. During the decades following World War II, the Western world saw an increasing confidence among the working population and social scientists alike that most people would have occupational careers characterized by upward mobility and by ‘good jobs’. The breeding ground for this idea is commonly dated to the mid- to late nineteenth century, a period characterized by tremendous economic, social and institutional change, including industrialization, mass communication and educational expansion. These modernization processes are expected to have caused changes in status attainment over the course of people’s careers. Across the social spectrum, the population at large is predicted to have had more successful careers. I study the development of occupational status over people’s careers in the period 1865 to 1940. I explain career success by studying the effects of individual characteristics, such as experience and social background, and the influence of regional modernization processes, such as educational expansion and industrialization. Moreover, I assess whether the effects of individual characteristics on career attainment changed over time and according to regional modernization processes. Unlike research focusing on specific occupational groups and localities, this dissertation uses data on the careers of a random sample of the male and female population nationwide. The Historical Sample of the Netherlands (HSN) contains information on the occupational careers of 8,291 men and 4,611 women who were present on the labour market between 1865 and 1940. The HSN is an excellent new database for the longitudinal study of male and female careers, covering the whole of the Netherlands. To include modernization processes at a regional level we have consulted several sources to collect data on regional modernization processes, such as industrialization, educational expansion and mass transport. The sources generally comprise official statistics or registers, and include the annual reviews on educational participation (Verslagen voor het hoger, middelbaar en lager onderwijs) and safety reports on steam engines drawn from the ‘Registers of the Dutch Department for Steam Engineering’. In addition to studying the careers of individuals, I study one of the mechanisms expected to have brought about changes in individual mobility outcomes: the hiring behaviour of employers. According to theories of industrialism, modernization processes caused employers to recruit employees increasingly on the basis of achieved characteristics, such as qualifications and experience, rather than ascribed characteristics, such as religious affiliation and social background. I study ascription- and achievement-based hiring by analysing the requirements stipulated by employers in job advertisements in Dutch newspapers in the period 1870 to 1939. One main conclusion is that individual differences in resources e.g., experience and schooling were clearly important for status attainment of men and women in the nineteenth and early twentieth centuries. Another is that while the classic expectation of increasing career success due to modernization processes was supported, no indication was found that the mechanisms of status attainment changed in response to modernization processes

Nanoprocessing of materials using ultrashort laser pulses involves a number of concurrent fundamental physical processes. Due to different time and spatial scales of activation, however, these processes are difficult to study within the frames of a single computational model on one hand, and yet not possible to isolate in the experimental analysis on the other hand. In their detailed investigation, the transient character of the nonequilibrium states of matter induced with a short laser pulse hampers the applicability of continuum approaches, but classical molecular dynamics simulations are usually limited in the system sizes. In this work, a molecular dynamics based model coupled to a continuum description of the photo-excited free carrier's dynamics and implemented in parallel algorithm is extended to the scale directly accessible in the experiment. This allows for the first time a direct comparison to experimental data. The essential mechanisms responsible for the sh ort laser pulse surface nanostructuring are analyzed in the complex dynamics of competing processes simultaneously involved into the nanostructures generation process. The modeling and experiment show a very good agreement and predict a new opportunity for fabrication of nanoparticle structures and the surface subpatterning.

Objective: ADAM proteases are important mediators of tumor growth, invasion and angiogenesis. As such, ADAM8 is of clinical significance, since glioma patient survival correlates inversely with ADAM8 expression levels. In this respect we hypothesised that ADAM8 has a therapeutic window in high-grade[for full text, please go to the a.m. URL], 64. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC)

Two-jet production in deep-inelastic electron-proton scattering has been studied for $160, Comment: 26 pages, latex, 9 figures appended as uuencoded file

The heteroepitaxy of III-V semiconductors on silicon is a promising approach for making silicon a photonic platform for on-chip optical interconnects and quantum optical applications. Monolithic integration of both material systems is a long-time challenge, since different material properties lead to high defect densities in the epitaxial layers. In recent years, nanostructures however have shown to be suitable for successfully realising light emitters on silicon, taking advantage of their geometry. Facet edges and sidewalls can minimise or eliminate the formation of dislocations, and due to the reduced contact area, nanostructures are little affected by dislocation networks. Here we demonstrate the potential of indium phosphide quantum dots as efficient light emitters on CMOS-compatible silicon substrates, with luminescence characteristics comparable to mature devices realised on III-V substrates. For the first time, electrically driven single-photon emission on silicon is presented, meeting the wavelength range of silicon avalanche photo diodes' highest detection efficiency.

We integrate the MHD ideal equations of a slender flux tube to simulate the internal plasma dynamics of coronal post-flare loops. We study the onset and evolution of the internal plasma instability to compare with observations and to gain insight into physical processes and characteristic parameters associated with flaring events. The numerical approach uses a finite-volume Harten-Yee TVD scheme to integrate the 1D1/2 MHD equations specially designed to capture supersonic flow discontinuities. We could reproduce the observational sliding down and upwardly propagating of brightening features along magnetic threads of an event occurred on October 1st, 2001. We show that high--speed downflow perturbations, usually interpreted as slow magnetoacoustic waves, could be better interpreted as slow magnetoacoustic shock waves. This result was obtained considering adiabaticity in the energy balance equation. However, a time--dependent forcing from the basis is needed to reproduce the reiteration of the event which resembles observational patterns -commonly known as quasi--periodic pulsations (QPPs)- which are related with large scale characteristic longitudes of coherence. This result reinforces the interpretation that the QPPs are a response to the pulsational flaring activity., Accepted MNRAS, 10 pages, 14 figures, 1 table