Thomas Eichhorn

Test beam measurements at the test beam facilities of DESY have been conducted to characterise the performance of the EUDET-type beam telescopes originally developed within the EUDET project. The beam telescopes are equipped with six sensor planes using MIMOSA26 monolithic active pixel devices. A programmable Trigger Logic Unit provides trigger logic and time stamp information on particle passage. Both data acquisition framework and offline reconstruction software packages are available. User devices are easily integrable into the data acquisition framework via predefined interfaces. The biased residual distribution is studied as a function of the beam energy, plane spacing and sensor threshold. Its standard deviation at the two centre pixel planes using all six planes for tracking in a 6\,GeV electron/positron-beam is measured to be $(2.88\,\pm\,0.08)\,\upmu\meter$.Iterative track fits using the formalism of General Broken Lines are performed to estimate the intrinsic resolution of the individual pixel planes. The mean intrinsic resolution over the six sensors used is found to be $(3.24\,\pm\,0.09)\,\upmu\meter$.With a 5\,GeV electron/positron beam, the track resolution halfway between the two inner pixel planes using an equidistant plane spacing of 20\,mm is estimated to $(1.83\,\pm\,0.03)\,\upmu\meter$ assuming the measured intrinsic resolution. Towards lower beam energies the track resolution deteriorates due to increasing multiple scattering. Threshold studies show an optimal working point of the MIMOSA26 sensors at a sensor threshold of between five and six times their RMS noise. Measurements at different plane spacings are used to calibrate the amount of multiple scattering in the material traversed and allow for corrections to the predicted angular scattering for electron beams.

Bruton's tyrosine kinase (BTK) inhibitors such as ibrutinib hold a prominent role in the treatment of B cell malignancies. However, further refinement is needed to this class of agents, particularly in terms of adverse events (potentially driven by kinase promiscuity), which preclude their evaluation in nononcology indications. Here, we report the discovery and preclinical characterization of evobrutinib, a potent, obligate covalent inhibitor with high kinase selectivity. Evobrutinib displayed sufficient preclinical pharmacokinetic and pharmacodynamic characteristics which allowed for in vivo evaluation in efficacy models. Moreover, the high selectivity of evobrutinib for BTK over epidermal growth factor receptor and other Tec family kinases suggested a low potential for off-target related adverse effects. Clinical investigation of evobrutinib is ongoing in several autoimmune diseases, including multiple sclerosis, rheumatoid arthritis, and systemic lupus erythematosus.

Abstract Glycosylation is a key critical quality attribute for monoclonal antibodies and other recombinant proteins because of its impact on effector mechanisms and half‐life. In this study, a variety of compounds were evaluated for their ability to modulate glycosylation profiles of recombinant monoclonal antibodies produced in Chinese hamster ovary cells. Compounds were supplemented into the cell culture feed of fed‐batch experiments performed with a CHO K1 and a CHO DG44 cell line expressing a recombinant immunoglobulin G1 (IgG1). Experiments were performed in spin tubes or the ambr®15 controlled bioreactor system, and the impact of the compounds at various concentrations was determined by monitoring the glycosylation profile of the IgG and cell culture parameters, such as viable cell density, viability, and titer. Results indicate that the highest impact on mannosylation was achieved through 15 µM kifunensine supplementation leading to an 85.8% increase in high‐mannose containing species. Fucosylation was reduced by 76.1% through addition of 800 µM 2‐F‐peracetyl fucose. An increase of 40.9% in galactosylated species was achieved through the addition of 120 mM galactose in combination with 48 µM manganese and 24 µM uridine. Furthermore, 6.9% increased sialylation was detected through the addition of 30 µM dexamethasone in combination with the same manganese, uridine, and galactose mixture used to increase total galactosylation. Further compounds or combinations of additives were also efficient at achieving a smaller overall glycosylation modulation, required, for instance, during the development of biosimilars. To the best of our knowledge, no evaluation of the efficacy of such a variety of compounds in the same cell culture system has been described. The studied cell culture media additives are efficient modulators of glycosylation and are thus a valuable tool to produce recombinant glycoproteins.

A common technique for analysis of protein glycosylation is HPLC coupled to mass spectrometry (LC-MS). However, analysis is challenging due to a low abundance of glycopeptides in complex protein digests, microheterogeneity at the glycosylation site, ion suppression effects, and competition for ionization by coeluting peptides. Specific sample preparation is necessary for a comprehensive and site-specific glycosylation analysis by MS. In this study we qualitatively compared hydrophilic interaction chromatography (HILIC) and hydrazine chemistry for the enrichment of all N-linked glycopeptides and titanium dioxide for capturing sialylated glycopeptides from a complex peptide mixture. Bare silica, microcrystalline cellulose, amino-, amide- (TSKgel Amide-80), and sulfobetaine-(ZIC-HILIC) bonded phases were evaluated for HILIC enrichment. The experiments revealed that ZIC-HILIC and TSKgel Amide-80 are very specific for capturing glycopeptides under optimized conditions. Quantitative analysis of N-glycosidase F-released and 2-aminobenzamide-labeled glycans of a ZIC-HILIC-enriched monoclonal antibody demonstrated that glycopeptides could be enriched without bias for particular glycan structures and without significant losses. Sialylated glycopeptides could be efficiently enriched by titanium dioxide and in addition to HILIC both methods enable a comprehensive analysis of protein glycosylation by MS. Enrichment of N-linked glycopeptides by hydrazine chemistry resulted in lower peptide recovery using a more complex enrichment scheme.

Abstract Spontaneous isopeptide bond formation, a stabilizing posttranslational modification that can be found in gram-positive bacterial cell surface proteins, has previously been used to develop a peptide-peptide ligation technology that enables the polymerization of tagged-proteins catalyzed by SpyLigase. Here we adapted this technology to establish a novel modular antibody labeling approach which is based on isopeptide bond formation between two recognition peptides, SpyTag and KTag. Our labeling strategy allows the attachment of a reporting cargo of interest to an antibody scaffold by fusing it chemically to KTag, available via semi-automated solid-phase peptide synthesis (SPPS), while equipping the antibody with SpyTag. This strategy was successfully used to engineer site-specific antibody-drug conjugates (ADCs) that exhibit cytotoxicities in the subnanomolar range. Our approach may lead to a new class of antibody conjugates based on peptide-tags that have minimal effects on protein structure and function, thus expanding the toolbox of site-specific antibody conjugation.

Industrial fed-batch cultivation of mammalian cells is used for the production of therapeutic proteins such as monoclonal antibodies. Besides medium ensuring initial growth, feeding is necessary to improve growth, viability and antibody production. Established processes include a slight acidic main feed and a separate alkaline feed containing l-tyrosine and l-cysteine. Since l-cysteine is not stable at neutral pH, a new derivative, S-sulfocysteine, was tested in neutral pH feeds. In small scale fed-batch processes, the S-sulfocysteine process yielded a comparable maximum viable cell density, prolonged viability and increased titer compared to the two feed system. Bioreactor experiments confirmed the increase in specific productivity. In depth characterization of the monoclonal antibody indicated no change in the glycosylation, or charge variant pattern whereas peptide mapping experiments were not able to detect any integration of the modified amino acid in the sequence of the monoclonal antibody. Finally, the mechanism of action of S-sulfocysteine was investigated, and results pointed out the anti-oxidative potential of the molecule, mediated through an increase in superoxide dismutase enzyme levels and in the total intracellular glutathione pool. Finally, we propose that the increase in specific productivity obtained in the S-sulfocysteine process results from the anti-oxidative properties of the molecule.

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In the last years, the sharing economy has emerged as an alternative to traditional exchanges, introducing the idea that users can grant other users temporary access to their goods and services for economic compensation. This shift was made largely possible by technological evolutions: Sharing platforms, which match users who share (providers) with users willing to pay for access (consumers), are based online and many services are available exclusively through a smartphone.

EUDAQ is a generic data acquisition software developed for use in conjunction with common beam telescopes at charged particle beam lines. Providing high-precision reference tracks for performance studies of new sensors, beam telescopes are essential for the research and development towards future detectors for high-energy physics. As beam time is a highly limited resource, EUDAQ has been designed with reliability and ease-of-use in mind. It enables flexible integration of different independent devices under test via their specific data acquisition systems into a top-level framework. EUDAQ controls all components globally, handles the data flow centrally and synchronises and records the data streams. Over the past decade, EUDAQ has been deployed as part of a wide range of successful test beam campaigns and detector development applications.

In this article, we examine changes in family climate during the first Covid‐19‐related lockdown in Germany. We compare the perspectives of mothers and adolescents to explore whether the factors of perceived changes in family climate are systematically and significantly different between these groups. We measure family climate as positive emotional climate, a sub‐dimension of the family environment scale, to capture a feeling of cohesion and emotional openness within the family. Based on family system theory and the family stress model, we expect an overall deterioration in family climate due to increased environmental adaptation in the pandemic. Furthermore, we expect family climate to deteriorate less when families have economic and social resources available. On the other hand, we assume that being employed and/or primarily responsible for family care relates to a stronger decline in the family climate. We employ longitudinal survey data (AID:A) from around 300 German families with children aged nine to 17 and apply individual fixed effects models to investigate changes in family climate from 2019 to 2020. Almost half of our respondents report a decrease in family climate. For mothers, the share of unpaid care work at home is the only significant predictor: Mothers doing more than 80% of the chores and childcare feel a greater decrease in family climate. For adolescents, however, being at risk of poverty and having less frequent family activities are important predictors of stronger decreases in family climate. In summary, our results illustrate the relevance of distinguishing between the perspective of children and parents in family studies.

The agri-environment-climate measures of the European Union Common Agricultural Policy are incentives aiming to reduce negative environmental impacts and increase positive effects generated from agriculture. Several criticisms have been addressed to their efficiency and effectiveness and thus, the design of innovative contract solutions is currently suggested. Among the novel contractual solutions, there are result-based payments, collective implementation of measures, the engagement of private and business actors in value chains, and new forms of land tenure systems coupled with environmental clauses. Little is known about the factors at interplay influencing farmers’ decision to uptake such contracts. The present paper investigates the acceptability determinants of the above-mentioned novel contractual solutions concerning a sample of nearly 1900 farmers from 10 European Union countries. The analysis is based on a questionnaire built through a common research framework. We apply ordered logistic regressions: both proportional and partial proportional odds models are used. Farmers’ preferences are interpreted by splitting the innovative contractual solutions into 13 individual contractual features which are then modeled in combination with the structural characteristics of the farms and the sociodemographic and behavioral characteristics of the farmers. We estimate farmers’ willingness to enroll in result-based, collective, value-chain, and land tenure contracts and highlight the positive and negative factors potentially influencing farmers’ acceptability of each type of contract.

This report presents results of a large-scale quantitative survey of European citizens on the topic of participation in the sharing economy. Based on a model of divides in sharing participation, it examines levels of engagement among Europeans, socioeconomic antecedents, motives for sharing participation as well as Internet skills and access. It differentiates reasons for non-participation and examines outcomes of both consumptive and productive participation. The report highlights sharing divides between participants and non-participants, active and passive participants, as well as occasional and professional providers in the sharing economy. It is part of a European Union Horizon 2020 Research Project on the sharing economy: "Ps2Share Participation, Privacy, and Power in the Sharing Economy". We aim to foster awareness of the consequences of the sharing economy for the way people behave, think, interact, and socialize across Europe. Our overarching objective is to identify key challenges of the sharing economy and improve Europe’s digital services through providing recommendations to Europe’s institutions.

Sharing economy platforms have grown to offer various commercial opportunities to a growing but still limited user base. We conceptualize engagement in the sharing economy as a form of online participation, and apply a digital inequalities perspective to examine the social stratification of commercial sharing. Based on the Internet access model established by Van Dijk, we analyze the effects of social structural antecedents on various access stages. Initial studies indicate that the sharing economy is characterized by second-order consumption, addressing user wants more than needs. Therefore, we draw on Bourdieu to complement Van Dijk’s model through a habitual perspective. Analyzing data collected in a survey of more than 6000 individuals from 12 European countries, we find that while social structural antecedents are critical in explaining initial usage of sharing services, their effect on repeat usage is less evident. Some indicators, such as education and social capital, even negatively relate to usage intensity. In turn, we find that a habitus of innovativeness and community-orientation significantly bolsters initial usage, but materialism, rather than material requirements, characterizes higher levels of engagement in the sharing economy.

EUTelescope is a modular, comprehensive software framework for the reconstruction of particle trajectories recorded with beam telescopes. Its modularity allows for a flexible usage of processors each fulfilling separate tasks of the reconstruction chain such as clustering, alignment and track fitting. The framework facilitates the usage of any position sensitive device for both the beam telescope sensors as well as the device under test and supports a wide range of geometric arrangements of the sensors. In this work, the functionality of the EUTelescope framework as released in v2.2 and its underlying dependencies are discussed. Various use cases with emphasis on the General Broken Lines advanced track fitting methods give examples of the work flow and capabilities of the framework.

This report presents recommendations aimed at facilitating a European sharing economy that is participatory, privacy-friendly and empowering. It is part of a European Union Horizon 2020 Research Project on the sharing economy: Ps2Share ‘Participation, Privacy, and Power in the Sharing Economy’ (ps2share.eu). The presented recommendations are derived from research focused on “Non-Participation, Inequalities, and Exclusion” in the sharing economy, encompassing a systematic literature review on participation in the sharing economy, focus group discussions among Millennials in several European countries, and a large-scale survey of citizens of twelve European countries. The resulting recommendations are addressed to five distinct audiences: (1) Providers, (2) consumers, (3) sharing economy platforms, (4) educators, and (5) policy makers.

During the scheduled high luminosity upgrade of LHC, the world's largest particle physics accelerator at CERN, the position sensitive silicon detectors installed in the vertex and tracking part of the CMS experiment will face more intense radiation environment than the present system was designed for. To upgrade the tracker to required performance level, extensive measurements and simulations studies have already been carried out. A defect model of Synopsys Sentaurus TCAD simulation package for the bulk properties of proton irradiated devices has been producing simulations closely matching with measurements of silicon strip detectors. However, the model does not provide expected behavior due to the fluence increased surface damage. The solution requires an approach that does not affect the accurate bulk properties produced by the proton model, but only adds to it the required radiation induced properties close to the surface. These include the observed position dependency of the strip detector's charge collection efficiency (CCE). In this paper a procedure to find a defect model that reproduces the correct CCE loss, along with other surface properties of a strip detector up to a fluence $1.5\times10^{15}$ 1 MeV n$_{\textrm{eq}}$ cm$^{-2}$, will be presented. When applied with CCE loss measurements at different fluences, this method may provide means for the parametrization of the accumulation of oxide charge at the SiO2/Si interface as a function of dose.

A new pixel detector for the CMS experiment was built in order to cope with the instantaneous luminosities anticipated for the Phase~I Upgrade of the LHC. The new CMS pixel detector provides four-hit tracking with a reduced material budget as well as new cooling and powering schemes. A new front-end readout chip mitigates buffering and bandwidth limitations, and allows operation at low comparator thresholds. In this paper, comprehensive test beam studies are presented, which have been conducted to verify the design and to quantify the performance of the new detector assemblies in terms of tracking efficiency and spatial resolution. Under optimal conditions, the tracking efficiency is $99.95\pm0.05\,\%$, while the intrinsic spatial resolutions are $4.80\pm0.25\,\mu \mathrm{m}$ and $7.99\pm0.21\,\mu \mathrm{m}$ along the $100\,\mu \mathrm{m}$ and $150\,\mu \mathrm{m}$ pixel pitch, respectively. The findings are compared to a detailed Monte Carlo simulation of the pixel detector and good agreement is found.

The future high luminosity upgrade of the LHC will necessitate radiation harder sensors for the CMS silicon strip tracker. CMS has instigated a campaign to identify a possible technology baseline for upcoming sensor generations. In addition to measurements, simulations can give an important insight into specific sensor properties. In this report, the concept of TCAD simulations is briefly explained, followed by sensor simulation results before and after irradiation. These results are then compared to measurements. The focus lies on the inter-strip capacitance C <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">int</sub> of silicon strip sensors.

The Large Hadron Collider (LHC) at CERN will be upgraded to a High Luminosity LHC in the year 2022, increasing the instantaneous luminosity by a factor of five. This will have major impacts on the experiments at the LHC, such as the Compact Muon Solenoid (CMS) experiment, and especially for their inner silicon tracking systems. Among other things, the silicon sensors used therein will be exposed to unprecedented levels of radiation damage, necessitating a replacement of the entire tracking detector. In order to maintain the excellent current performance, a new tracking detector has to be equipped with sensors of increased radiation hardness and higher granularity. The CMS experiment is undertaking an extensive R&D campaign in the search for the future silicon sensor technology baseline to be used in this upgrade. This thesis presents two methods suitable for use in this search: finite element TCAD simulations and test beam measurements. The simulations are focussed on the interstrip capacitance between sensor strips and are compared to measurements before and after the inclusion of radiation damage effects. A geometrical representation of the strip sensors used in the campaign has been found, establishing the predictive power of simulations. The test beam measurements make use of the high-precision pixel telescopes available at the DESY-II test beam facility. The performance of these telescopes has been assessed and their achievable pointing resolution has been found to be below 2 μm. Thin, epitaxial silicon is a candidate material for usage in radiation hard sensors for the future CMS tracking detector. Sample strip sensors of this material have been irradiated to fluences of up to 1.3 × 10^{16} neq/cm^2 with 800 MeV or 23 GeV protons. Test beam measurements with 5 GeV electrons have been performed to investigate the radiation hardness of epitaxial sensors using the pixel beam telescopes. The epitaxial device under test (DUT) has been integrated into the telescope and its software analysis framework. An alignment of DUT and telescope planes has been performed and traversing particle tracks reconstructed for the sensor analysis. Results show that the achievable resolution in the epitaxial silicon strip sensors is at the binary level. The measured charge collection efficiency for p-bulk sensors amounts to 80 % of pre-irradiation levels for fluences of 3 × 10^{15} neq /cm^2 and to over 65 % for Φ = 1.3 × 10^{16} neq /cm^2. Signal-to-noise levels at these fluence levels are 7.4 and 3.8, respectively. With particle tracks of various inclinations, the sharing of charge between sensor strips is investigated. Indications of possible charge losses at the sensor surface are described and evidence of commencing charge multiplication effects is presented. Sensors are also compared to thicker, non epitaxial sensors irradiated to the same fluence. From the obtained results, acquired from the first test beam measurements of irradiated epitaxial sensors ever performed, a complete picture of this material has been gained. It can be concluded that thin, p-bulk epitaxial silicon is sufficiently radiation hard for usage as an outer pixel detector sensor material. Der Large Hadron Collider (LHC) am CERN wird im Jahr 2022 zum High Luminosity LHC (HL-LHC) erweitert, indem die instantane Luminositat um den Faktor funf erhoht wird. Dies hat erhebliche Auswirkungen auf die Experimente am LHC, wie zum Beispiel das CMS Experiment, insbesonders auf deren Spurdetektoren. Die dort verwendeten Siliziumsensoren werden erheblichen Strahlenschadigungen ausgesetzt, wodurch ein Komplettaustausch des Detektors notwendig wird. Um die gegenwartige, ausgezeichnete Leistung des Spurdetektors auch im HL-LHC beibehalten zu konnen, muss dieser mit noch strahlenharteren Sensoren ausgestattet werden, die zudem noch eine erhohte Granularitat aufweisen. Eine Forschungskampagne innerhalb des CMS Experimentes sucht derzeit nach einer geeigneten Technologie fur die zukunftigen Siliziumsensoren. Die vorliegende Arbeit ist Teil dieses Projektes und benutzt zwei Methoden zur Untersuchung von Sensoreigenschaften: TCAD Simulationen und Teststrahlmessungen. Die Simulationen beschranken sich auf die Zwischenstreifenkapazitat in Streifensensoren und werden mit Messungen vor und nach Bestrahlung verglichen. Es wurde eine Struktur gefunden, die den in dieser Kampagne verwendeten Sensoren entspricht, und dadurch die Vorhersagefahigkeit von Simulationen erhoht. Fur die durchgefuhrten Teststrahlmessungen wurden die Prazisionsteleskope verwendet, die am DESY-II Teststrahl zur Verfugung stehen. Systematische Untersuchungen dieser Teleskope wurden durchgefuhrt und resultieren in einer Vorhersagegenauigkeit von unter 2 μm am Punkt des Testsensors. Dunnes, epitaktisch gewachsenes Silizium konnte ein geeignetes strahlenhartes Sensormaterial fur den zukunftigen CMS Spurdetektor sein. Sensoren dieses Materials wurden mit 800 MeV oder 23 GeV Protonen bis zu Fluenzen von 1, 3 × 10^{16} neq /cm^2 bestrahlt. Um die Strahlenharte von epitaktischen Sensoren zu bestimmen, wurden sie unter Verwendung der Teleskope mit 5 GeV Elektronen im DESY-II Teststrahl vermessen. Die Sensoren wurden in die Teleskope und in deren Auslese- und Analysesoftware integriert. Eine Prazisionsausrichtung von Sensoren und Teleskop wurde durchgefuhrt und durchquerende Teilchenspuren zur Sensoranalyse rekonstruiert. Die Analyseergebnisse zeigen, dass die epitaktischen Sensoren eine binare Auflosung erreichen. Die gemessene Ladungssammlungseffizienz fur p-Typ Sensoren betragt fur eine Fluenz von 3 × 10^{15} neq /cm^2 80 % des vor der Bestrahlung gemessenen Wertes. Fur Fluenzen der Grose Φ = 1, 3 × 10^{16} neq /cm^2 betragt dieser Wert 65 %. Mit Teilchenspuren aus verschiedenen Einfallswinkeln wird die Ladungsteilung zwischen Streifen untersucht, Indizien von Ladungsverlusten an der Sensoroberflache werden beschrieben und Anzeichen von beginnender Ladungsmultiplikation aufgezeigt. Die epitaktischen Sensoren werden auserdem mit dickeren, nicht epitaktischen Sensoren gleicher Fluenz verglichen. Aus den gewonnen Daten kann die Schlussfolgerung gezogen werden, dass dunnes, epitaktisch gewachsenes p-Typ Silizium ausreichend strahlenhart fur einen Einsatz als Sensormaterial in den auseren Lagen des Pixeldetektors ist.

The receptor tyrosine kinase MET is activated by hepatocyte growth factor binding, followed by phosphorylation of the intracellular kinase domain (KD) mainly within the activation loop (A-loop) on Y1234 and Y1235. Dysregulation of MET can lead to both tumor growth and metastatic progression of cancer cells. Tepotinib is a highly selective, potent type Ib MET inhibitor and approved for treatment of non-small cell lung cancer harboring METex14 skipping alterations. Tepotinib binds to the ATP site of unphosphorylated MET with critical π-stacking contacts to Y1230 of the A-loop, resulting in a high residence time. In our study, we combined protein crystallography, biophysical methods (surface plasmon resonance, differential scanning fluorimetry), and mass spectrometry to clarify the impacts of A-loop conformation on tepotinib binding using different recombinant MET KD protein variants. We solved the first crystal structures of MET mutants Y1235D, Y1234E/1235E, and F1200I in complex with tepotinib. Our biophysical and structural data indicated a linkage between reduced residence times for tepotinib and modulation of A-loop conformation either by mutation (Y1235D), by affecting the overall Y1234/Y1235 phosphorylation status (L1195V and F1200I) or by disturbing critical π-stacking interactions with tepotinib (Y1230C). We corroborated these data with target engagement studies by fluorescence cross-correlation spectroscopy using KD constructs in cell lysates or full-length receptors from solubilized cellular membranes as WT or activated mutants (Y1235D and Y1234E/1235E). Collectively, our results provide further insight into the MET A-loop structural determinants that affect the binding of the selective inhibitor tepotinib.

Adolescence is marked by rapid biological and psychosocial changes that profoundly impact parent–child communication in order to reorganize responsibilities and move toward a more egalitarian relationship. Therefore, our primary objective in the present study was to explore the influence of changing conflict frequency and intensity on the perceived level of closeness between parents and adolescents, considering the perspectives of both parties involved. Using 10-wave longitudinal data with measures of parents (n = 17,005) and their children (n = 15,841) aged seven to 16 from the German Panel “Analysis of Intimate Relationships and Family Dynamics” (pairfam), the present study used fixed-effects models to address the research goal. The findings indicate that, for parents and adolescents, an increase in both conflict frequency and intensity corresponds to a more pronounced decline in closeness. Higher levels of initial closeness when the participants entered the survey resulted in milder decreases in closeness when conflict intensity was higher, a pattern observed for both parents and adolescents. Regarding conflict frequency, no impact of initial closeness was discerned among parents, while an opposing effect was found among adolescents. These findings shed light on changes in parent–child communication during the transition from early to middle adolescence, underscoring the need for further exploration of the closeness–conflict association.

Das durch das Bundesministerium für Familie, Senioren, Frauen und Jugend geförderte Bundesprogramm des Europäischen Sozialfonds „Stark im Beruf – Mütter mit Migrationshintergrund steigen ein“ soll Müttern mit Migrationshintergrund den Erwerbseinstieg erleichtern und ihren Zugang zu vorhandenen Angeboten zur Arbeitsmarktintegration verbessern. Der vorliegende Beitrag erläutert Erklärungsansätze für eine geringere Erwerbsbeteiligung von Frauen mit Migrationshintergrund in Deutschland und stellt darauf Bezug nehmend die Maßnahmenerfolge des ESF-Bundesprogramms „Stark im Beruf“ vor. Auswertungen der im Rahmen des Programms erhobenen Daten zeigen, dass Teilnehmerinnen nach Programmabschluss mit einer höheren Wahrscheinlichkeit eine Beschäftigung oder eine schulische oder berufliche Ausbildung aufnehmen, wenn sie eher berufsnahe Module belegt haben und sie bereits bei Programmeintritt bessere Voraussetzungen hinsichtlich ihres übertragbaren Humankapitals und ihrer Nähe zum Arbeitsmarkt in Deutschland mitbringen. Teilnehmerinnen, die über einen längeren Zeitraum arbeitslos gemeldet sind oder sich im SGB II-Bezug befinden, sowie Teilnehmerinnen mit kleinen Kindern im Haushalt haben hingegen eine niedrigere Programmerfolgswahrscheinlichkeit. Abschließend werden im Beitrag Implikationen dieser Ergebnisse sowie die Limitationen der Analysen aufgezeigt.

During the high luminosity upgrade of the LHC (HL-LHC) the CMS tracking system will face a more intense radiation environment than the present system was designed for. In order to design radiation tolerant silicon sensors for the future CMS tracker upgrade it is fundamental to complement the measurement with device simulation. This will help in both the understanding of the device performance and in the optimization of the design parameters. One of the important ingredients of the device simulation is to develop a radiation damage model incorporating both bulk and surface damage. In this paper we will discuss the development of a radiation damage model by using commercial TCAD packages (Silvaco and Synopsys), which successfully reproduce the recent measurements like leakage current, depletion voltage, interstrip capacitance and interstrip resistance, and provides an insight into the performance of irradiated silicon strip sensors.

While the tracking detectors of the ATLAS and CMS experiments have shown excellent performance in Run 1 of LHC data taking, and are expected to continue to do so during LHC operation at design luminosity, both experiments will have to exchange their tracking systems when the LHC is upgraded to the high-luminosity LHC (HL-LHC) around the year 2024. The new tracking systems need to operate in an environment in which both the hit densities and the radiation damage will be about an order of magnitude higher than today. In addition, the new trackers need to contribute to the first level trigger in order to maintain a high data-taking efficiency for the interesting processes. Novel detector technologies have to be developed to meet these very challenging goals. The German groups active in the upgrades of the ATLAS and CMS tracking systems have formed a collaborative "Project on Enabling Technologies for Silicon Microstrip Tracking Detectors at the HL-LHC" (PETTL), which was supported by the Helmholtz Alliance "Physics at the Terascale" during the years 2013 and 2014. The aim of the project was to share experience and to work together on key areas of mutual interest during the R&amp;D phase of these upgrades. The project concentrated on five areas, namely exchange of experience, radiation hardness of silicon sensors, low mass system design, automated precision assembly procedures, and irradiations. This report summarizes the main achievements.

This report is part of a European Union Horizon 2020 Research Project on the sharing economy: Ps2Share ‘Participation, Privacy, and Power in the Sharing Economy’ (www.ps2share.eu). It presents the recommendations derived from Work Package 4 “Non-Participation, Inequalities, and Exclusion” within the Ps2Share project. Work Package 4 encompassed a systematic literature review on participation in the sharing economy (Andreotti, Anselmi, Eichhorn, Hoffmann, & Micheli, 2017), focus group discussions among Millennials in several European countries (Ranzini, Newlands, Anselmi, Andreotti, Eichhorn, Etter, Hoffmann, Jurss, & Lutz, 2017) and a largescale survey of citizens of twelve European countries (Andreotti, Anselmi, Eichhorn, Hoffmann, Jurss, & Micheli, 2017). The project also included three deliverables on the topic of privacy in the sharing economy: a comprehensive literature review (Ranzini, Etter, Lutz, & Vermeulen, 2017), a large-scale survey report (Ranzini, Etter, & Vermeulen, 2017) as well as recommendations on a more privacy-friendly sharing economy in Europe (Ranzini, Kusber, Vermeulen, & Etter, 2018). In addition, three deliverables on power in the sharing economy were produced: a comprehensive literature review (Newlands, Lutz, & Fieseler, 2017a), a large-scale survey report (Newlands, Lutz, & Fieseler, 2017b) as well as recommendations on a more empowering sharing economy in Europe (Newlands, Lutz, & Fieseler, 2018). Finally, two deliverables about platforms in the sharing economy formed part of the project: a comprehensive platform analysis report (Stanoevska-Slabeva, Lenz-Kesekamp, & Suter, 2017) and a set of platform design implications in the form of guidelines (Stanoevska-Slabeva, Lenz-Kesekamp, & Suter, 2018).

This data set contains: Cleaned data files of the 2017 survey on participation, privacy, and power in the sharing economy across 12 countries. Data are in sav (for SPSS), xlsx, and csv format. Survey questionnaires in 10 languages (zipped PDFs) Methodological Appendix This <strong>EU Horizon 2020 Research Project: Ps2Share</strong> was concerned with questions of participation, privacy, and power in the sharing economy. With funding granted by the European Commission's Horizon 2020 Growth Strategy, this one-year research project was conducted by a consortium of international researchers from Norway, Germany, The Netherlands, Italy, Denmark, and Switzerland. The emergence of innovative platforms has extended the notion of online sharing to the vibrant new domain of sharing of material goods and services. We call this phenomenon 'the sharing economy'. With companies such as Airbnb, Uber, Taskrabbit, and Transferwise dominating the market, user numbers of sharing services have skyrocketed and expect to grow further, enabling ever new avenues of economic and social interaction to appear. The sharing economy promises to provide more inclusive business opportunities for individuals of various skills levels and resource endowment. However, the public rhetoric of chances, growth, and inclusion frequently contrasts with the risks, concerns, disadvantages, and exclusion in the experience of a variety of users. These platforms, extending into the private and physical realm of their users, create compound privacy risks and increase the potential for exclusion and discrimination through ratings-based sanctioning. In facing the ongoing growth of the sharing economy, we are presented with a variety of challenges, which need to be addressed. With our research, we hope to facilitate public deliberation on desirable practices and policies. Our overarching objective is to identify key challenges of the sharing economy and improve Europe’s digital services through providing recommendations to Europe’s institutions. These will include schools and companies, as well as governmental and non-governmental organisations. In constructing policy, we aim to provide steps toward more modern regulatory and policymaking approaches, helping to create a more balanced digitized economy that is socially acceptable to all. We aim to foster better awareness of the consequences which technologies, networks, and new digital media have on the way people behave, think, interact, and socialise as persons, citizens, workers, and consumers across Europe. Further information and reports can be found at www.ps2share.eu Contact: Professor Christian Fieseler, BI Norwegian Business School, christian.fieseler@bi.no

This data set contains: Cleaned data files of the 2017 survey on participation, privacy, and power in the sharing economy across 12 countries. Data are in sav (for SPSS), xlsx, and csv format. Survey questionnaires in 10 languages (zipped PDFs) Methodological Appendix This <strong>EU Horizon 2020 Research Project: Ps2Share</strong> was concerned with questions of participation, privacy, and power in the sharing economy. With funding granted by the European Commission's Horizon 2020 Growth Strategy, this one-year research project was conducted by a consortium of international researchers from Norway, Germany, The Netherlands, Italy, Denmark, and Switzerland. The emergence of innovative platforms has extended the notion of online sharing to the vibrant new domain of sharing of material goods and services. We call this phenomenon 'the sharing economy'. With companies such as Airbnb, Uber, Taskrabbit, and Transferwise dominating the market, user numbers of sharing services have skyrocketed and expect to grow further, enabling ever new avenues of economic and social interaction to appear. The sharing economy promises to provide more inclusive business opportunities for individuals of various skills levels and resource endowment. However, the public rhetoric of chances, growth, and inclusion frequently contrasts with the risks, concerns, disadvantages, and exclusion in the experience of a variety of users. These platforms, extending into the private and physical realm of their users, create compound privacy risks and increase the potential for exclusion and discrimination through ratings-based sanctioning. In facing the ongoing growth of the sharing economy, we are presented with a variety of challenges, which need to be addressed. With our research, we hope to facilitate public deliberation on desirable practices and policies. Our overarching objective is to identify key challenges of the sharing economy and improve Europe’s digital services through providing recommendations to Europe’s institutions. These will include schools and companies, as well as governmental and non-governmental organisations. In constructing policy, we aim to provide steps toward more modern regulatory and policymaking approaches, helping to create a more balanced digitized economy that is socially acceptable to all. We aim to foster better awareness of the consequences which technologies, networks, and new digital media have on the way people behave, think, interact, and socialise as persons, citizens, workers, and consumers across Europe. Further information and reports can be found at www.ps2share.eu Contact: Professor Christian Fieseler, BI Norwegian Business School, christian.fieseler@bi.no

At DLR, CMC materials and structures based on the LSI process have been developed since the late 1980`s. In the first step of the LSI process, a CFRP preform is made using common technologies like resin transfer moulding (RTM), autoclave technique or warm pressing. Subsequently, the CFRP preform is pyrolysed and infiltrated by molten silicon. Thereby, the silicon reacts with carbon, forming a SiC matrix, leading to the final C/C-SiC material. Up to now, carbon fibre 2D woven fabrics have been used for the manufacture of thin walled, C/C-SiC structures like nose caps for thermal protection systems of spacecraft. However, for highly loaded, lightweight structures like nozzles or combustion chambers, the use of 2D woven fabrics is critical, due to the inadequate drapability and the resulting, limited strength. Therefore, CFRP-preforms based on filament winding, a well known process for the industrial production of tubular structures, have been adapted to the LSI process. Thereby, the winding angle of the fibre was varied systematically. In the resulting C/C-SiC material a strong influence of the fibre orientation to the mechanical properties was observed. In this presentation the manufacturing of tubular C/C-SiC structures via filament winding is described in detail and first results regarding microstructure and mechanical behaviour are given.

Offentliche Bibliotheken sind wichtige Statten, in denen soziokulturelle Ausdrucksformen und Zukunftserwartungen der Kinder gepragt werden. Eine Hauptthese des Vortrags besteht darin, dass diese Ausdrucksformen und Erwartungshaltungen auf einer komplexen Medienkultur beruhen. Darum mussen sowohl virtuelle wie auch reale Bibliotheken den jungen Benutzern Produkte von hoher Qualitat und in allen semiotischen Prasentationsformen Text, Ton, Bild bereitstellen. Ebenso erforderlich ist ein engagierter Dialog zwischen Benutzern und Bibliotheksmitarbeitern, die in der qualitativen Beurteilung der verschiedenen Prasentationsformen versiert sind. Diese Hauptthese wird gestutzt durch eine kurze Analyse globaler Trends in der Medienbenutzung durch Kinder und ihrer soziokulturellen Unterschiede sowie durch Einzelbeispiele der Herausforderungen, vor denen multimodale Bibliotheken stehen.

(Dr.-Ing. Joachim BENNER, Forschungszentrum Karlsruhe, Institut fur Angewandte Informatik, Postfach 3640, D76021 Karlsruhe, Joachim.Benner@iai.fzk.de) (Dr.-Ing. Kai-Uwe KRAUSE, Thomas EICHHORN, Landesbetrieb Geoinformation und Vermessung, Freie und Hansestadt Hamburg, Sachsenkamp 4, 20097 Hamburg, {kai-uwe.krause;thomas.eichhorn}@gv.hamburg.de) (Yvonne MULLER, Deutsche Gesellschaft fur Technische Zusammenarbeit (GTZ) GmbH, Belvederska 5, 81000 Podgorica, Montenegro, yvonne.mueller@gtz.de)

Das Open-Access Buch vergleicht die explorative Tympanoskopie mit Verfahren intratympanaler Steroidinjektionen.

Zusammenfassung Die akut aufgetretene, einseitige, idiopathische sensorineurale Hörminderung (ISSNHL) ist eine Erkrankung, die das Befinden der betroffenen Erkrankten in der Regel erheblich einschränkt und sie meist auch recht schnell dazu veranlasst, ärztliche Hilfe aufzusuchen. Therapeutisch erfolgt derzeit weltweit meistens, zumindest als Erstmaßnahme, eine systemische Kortikoidgabe, sei es in oraler, in der Regel jedoch in parenteraler (intravenöser) Form.

Zusammenfassung Eine Reihe von Publikationen befasst sich mit der Frage, welche Patienten-bezogenen epidemiologischen Daten und zeitgleich zum Hörsturz aufgetretenen Beschwerden auf die Höhe des initialen Hörverlustes wie auch den nach einer Therapie erreichten Hörerfolg Einfluss genommen haben können [29, 30, 33, 57, 65, 97, 101]. In diesem Kapitel soll es zunächst darum gehen, nach Patientenuntergruppen zu fahnden, bei denen sich vor Behandlungsbeginn die Ausgangslage in Bezug auf den Anfangshörverlust als besonders vorteilhaft resp. unvorteilhaft darstellt. Darüber hinaus interessierte uns, ob sich ggf. die Kombination des Auftretens einzelner Ausgangsparameter besonders günstig oder ungünstig auf die weitere Entwicklung der ISSNHL ausgewirkt hatte.

Zusammenfassung Plötzlich aufgetretene Perilymphfisteln (PLF) unterscheiden sich phänomenologisch oft nicht vom sog. Hörsturz. Neben der akut eingetretenen Hörminderung, die in der Regel sehr ausgeprägt ist – es kommt zum Abfließen von Perilymphe aus dem Innenohr –, tritt oft zeitgleich mit dem Hörverlust ein heftiger Schwindel auf, gelegentlich zusätzlich begleitet von Tinnitus auf dem betroffenen Ohr.

In this study, based on survey data collected from twelve European countries (N=6111), we build on the digital technology access model to examine the role of gender in access to the sharing economy.Applying a "doing gender" perspective, we find that men capitalise on a stronger economic position and a more pronounced orientation to explore new technology to gain access to sharing services, while women rely more on cultural and social capital.We relate our findings to intersectionality theory by discussing how class and gender intersect in facilitating access to the sharing economy.

On January 17th 2018, a forum on a possible Joint Research Activity on a future common Beam Telescope was held during the 6th Beam Telescopes and Test Beams Workshop (BTTB) in Zurich, Switzerland. The BTTB workshop aims at bringing together the community involved in beam tests. It therefore offers a suitable platform to induce community-wide discussions. The forum and its discussions were well received and the participants concluded that appropriate actions should be undertaken promptly. Specific hardware and software proposals were discussed, with an emphasis on improving current common EUDET-type telescopes based on Mimosa26 sensors towards higher trigger rate capabilities in convolution with considerably improved time resolution. EUDAQ as a common top level DAQ and its modular structure is ready for future hardware. EUTelescope fulfils many requirements of a common reconstruction framework, but has also various drawbacks. Thus, requirements for a new common reconstruction framework were collected. A new common beam telescope evolves with the sensor decision and the whole package including a reconstruction framework depends on that decision.

On January 17th 2018, a forum on a possible Joint Research Activity on a future common Beam Telescope was held during the 6th Beam Telescopes and Test Beams Workshop (BTTB) in Zurich, Switzerland. The BTTB workshop aims at bringing together the community involved in beam tests. It therefore offers a suitable platform to induce community-wide discussions. The forum and its discussions were well received and the participants concluded that appropriate actions should be undertaken promptly. Specific hardware and software proposals were discussed, with an emphasis on improving current common EUDET-type telescopes based on Mimosa26 sensors towards higher trigger rate capabilities in convolution with considerably improved time resolution. EUDAQ as a common top level DAQ and its modular structure is ready for future hardware. EUTelescope fulfils many requirements of a common reconstruction framework, but has also various drawbacks. Thus, requirements for a new common reconstruction framework were collected. A new common beam telescope evolves with the sensor decision and the whole package including a reconstruction framework depends on that decision.

US$18141 (US and Rest of World), € 11707 (Europe), £ 9260 (UK

2,5-Dihydroxybenzoic acid (DHB) is the matrix of choice for carbohydrate and glycopeptide analysis, but due to the inhomogeneous surface morphology of samples prepared with DHB, it is typically incompatible with automated measurements. We describe a simple and rapid method for the analysis of glycoproteins, which combines (a) reducing the complexity of the digest mixtures with glyco-specific enrichment and (b) subsequent LC-MALDI-TOF MS/MS analysis with DHB as MALDI matrix. All samples were prepared on hydrophobic sample plates with hydrophilic anchors 400 or 600 μm in diameter confining the sample dimensions. In a first step, the matrix was applied to the 384 sample spots (“anchors”) of a microtiter plate–shaped MALDI target. The LC eluate from CAP-RP-HPLC subsequently dissolved the DHB matrix confined to the hydrophobic boundaries of the anchors. Co-crystallization of glycopeptides in DHB suitable for the automated analysis was achieved. This method was applied to recombinant human inte-grin alpha and beta; glycosylation sites were identified and described. The MALDI-MSMS spectra of glycopeptides (N-linked type) include information about the structure of peptide moiety as well as the glycan part of the molecules. MALDI-TOF/TOF spectra permitted (a) the detection of N-linked glycopeptides by a neutral loss analysis across the entire LC-MALDI-MS/MS dataset, (b) the determination of the molecular weight of the pure peptide chain by typical fragmentation patterns, (c) the identification of the peptide part of the fragmented glycopeptide by means of simple database searching, and (d) initial information about the glycan composition and the attachment site. LC-MALDI-TOF/TOF on DHB matrix preparation is a powerful approach for the detailed characterization of glycoproteins.

Die umweltsoziologische Forschung nutzt das Konstrukt des Umweltbewusstseins, um individuelles Umwelthandeln zu erklaren. Aus Sicht der Praxistheorie wird dabei jedoch lediglich das kommunizierbare Wissen der Akteure berucksichtigt. Daruber hinaus verfugen diese Akteure jedoch auch uber nicht-kommunizierbares Wissen, welches fur ihre Handlungspraxis von Bedeutung ist. In diesem Beitrag untersuchen wir, in welches nicht-kommunizierbare Wissen Umweltbewusstsein eingebettet ist und dadurch seine weitere Bedeutung bezieht. In einer Sekundaranalyse werten wir Gruppendiskussionen zwischen Nutzer*innen der sog. Sharing Economy aus, um dieser Frage nachzugehen. Die Sharing Economy stellt hierbei einen speziellen Fall umweltbezogenen Konsums dar, der von ihren Nutzer*innen oft als Moglichkeit zur Reduktion von Umweltbelastungen wahrgenommen wird. Wir verwenden die Dokumentarische Methode nach Ralf Bohnsack, um vier Orientierungsrahmen der Nutzer*innen auszuarbeiten, welche ihr nicht-kommunizierbares Wissen abbilden. Im Anschluss diskutieren wir Gemeinsamkeiten und Widerspruche zu ihrem kommunizierbaren Wissen sowie die Relevanz der Betrachtung beider Aspekte fur die umweltsoziologische Forschung. Environmental sociological research uses the construct of environmental consciousness to explain individuals‘ decisions relating to the ecological environment of humans. From a practice theory perspective, environmental consciousness takes only such knowledge into account that can be communicated by actors. Additionally, actors also have non-communicative knowledge that is nonetheless relevant for their practice. In this article, we ask in what kind of non-communicative knowledge environmental consciousness is embedded and derives its meaning from. To address this question, we use group discussions between users of the sharing economy in a secondary analysis. The sharing economy is a specific case of environment-related consumption opportunity that users often perceive as a chance to reduce environmental stress. Applying the Documentary Method of Ralf Bohnsack, we work out four frameworks that reflect users‘ non-communicative knowledge of the sharing economy. We point out similarities and contradictions between communicative and non-communicative knowledge elements and discuss the relevance of considering both types of knowledge for environmental sociological research. (peer reviewed)

Abrasion determinations in various layer depths showed that the layer of the filling material Evicrol directly under the matrix-hardened surface is more abrasion-resistant than the matrix- hardened surface. From this it is concluded that it is good practice to overfill in making restorations of Evicrol and to remove a certain layer of material (approximately 0.25 mm, according to Fraunhofer).

The water absorption of Evicrol, its hardness, flexural strength and abrasion resistance were measured and compared with the values found for Adaptic and those for Kallocryl A as a non-filled polymethyl methacrylate plastic. The flexural strength and the abrasion resistance of Evicrol amount to those of Adaptic. The hardness of Evicrol falls also short of that of Adaptic. On the contrary, Evicrol behaves quite differently under water. It was found that the amound of water absorbed by Evicrol is some 3-fold greater than that absorbed by Adaptic, and that saturation is reached considerably slower.