The DH Course Registry: A Piece of the Puzzle in CLARIN’s Technical and Knowledge Infrastructure

This chapter presents the Digital Humanities Course Registry (DHCR) as part of CLARIN’s Technical and Knowledge Infrastructure. The DHCR is an initia-tive started to provide an overview of the growing number of training activities in the field of Digital Humanities around the world. The goal of the registry, which is run jointly with DARIAH, is to collect information on the rich offerings of different courses with the help of the community and to delineate an up-to-date picture of the teaching and training opportunities in the field. First, we will introduce the DHCR, its goals, genesis, and main features. Then we will elaborate on the DHCR’s position within CLARIN’s Technical Infrastructure and how it helps to address CLARIN’s agenda and strategic goals in terms of Technical Infrastruc-ture, Open Science, and especially the FAIR Principles. Particular attention will be paid to the results of a cross-national hackathon using data and metadata from the DHCR. Furthermore, we will examine the position of the DHCR within CLAR-IN’s Knowledge Infrastructure, which includes training and education

The Relationship Between Lava Fountaining and Vent Morphology for the 2014–2015 Holuhraun Eruption, Iceland, Analyzed by Video Monitoring and Topographic Mapping

Fissure eruptions are associated with lava fountains which often show complex distinct venting activity in pulsating form, and the development of characteristic morphological features such as scoria or spatter cones. Most morphological studies are based on observations of old structures and are not related to direct observations and systematic records of vent activity. The 2014–2015 Holuhraun eruption site, Iceland, offered an exceptional opportunity to study the location and evolution of these cones and their relationship to venting dynamics in unprecedented detail. Here we analyze records from lava fountain activity at distinguished vents, captured during the 2014–2015 Holuhraun eruption, and compare them with the morphology of spatter cones that developed. We conducted a fieldwork mapping project combining terrestrial laser scanning (TLS) and unmanned aerial vehicle (UAV) aerophoto techniques to characterize the cone morphologies. We recorded videos of the eruption and used edge detection and particle image velocimetry to estimate venting heights and particle velocities. We find that the number of active vents producing lava fountains decreases from 57 along the whole line of fire to 10 lava fountains at distinct vents during the first 5 days of the eruption. We suggest that this happens by channeling the magma supply in the subsurface developing conduits. Thereby we see that at the locations where spatter cone morphology developed, the strongest and the highest lava fountains with high ejection velocities were recorded on the very first days of the eruption. In addition, the sites that eventually developed moderate or weak cone morphologies were identified as less active lava fountain locations during the early stage of the eruption. The comparison of our topographic datasets shows that the spatter cones remained similar in shape but increased in size as the eruption progressed. In addition, we suggest that the observed changes in morphology may have affected lava ponding in the crater, which in turn strongly influenced the lava fountain heights. Our results improve the general understanding of landscape evolution in rift zones and demonstrate the close relationship between cone morphology and lava fountain activity at the onset of an eruption

REFIR- a multi-parameter system for near real-time estimates of plume-height and mass eruption rate during explosive eruptions

Meaningful forecasting of the atmospheric concentration and ground accumulation of volcanic ash during explosive eruptions requires detailed knowledge of the eruption source parameters. However, due to the large uncertainties in observations and limitations of current models used to make inferences from these, monitoring an ongoing eruption and quantifying the mass eruption rate in real-time is a considerable challenge. Within the EU supersite project “FutureVolc”, an integrated approach has been applied to develop a quasi-autonomous multi-parameter system, denoted “REFIR”, for monitoring volcanic eruptions in Iceland and assessing the eruption mass flow rate by inverting the plume height information and taking account of these uncertainties. REFIR has the capability to ingest and process streaming plume-height data provided by a multitude of ground based sensors, including C– and X-band radars and web-cam based plume height tracking systems. These observational data are used with a suite of plume models that also consider the current wind and other atmospheric conditions, providing statistically assessed best estimates of plume height and mass eruption rate. Provided instrumental data is available, near real-time estimates are obtained (the delay corresponding to the scan rate of data-providing instruments, presently of the order of minutes). Using the Hekla 2000, and Eyjafjallajökull 2010 eruptions in Iceland, the potential of REFIR is demonstrated and discussed through application to three scenarios. The system has been developed to provide maximum flexibility. A setup script assists the user in adapting to local conditions, allowing implementation of REFIR for any volcanic eruption site worldwide. REFIR is designed to be easily upgradable, allowing future extension of monitoring networks, learning from new events, and incorporation of new technologies and model improvements. This article gives an overview of the basic structure, models implemented, functionalities and the computational techniques of REFIR

from a better etiological understanding, through valid diagnosis, to more effective health care

Background Autism Spectrum Disorder (ASD) is a severe, lifelong neurodevelopmental disorder with early onset that places a heavy burden on affected individuals and their families. Due to the need for highly specialized health, educational and vocational services, ASD is a cost- intensive disorder, and strain on health care systems increases with increasing age of the affected individual. Methods The ASD-Net will study Germany’s largest cohort of patients with ASD over the lifespan. By combining methodological expertise from all levels of clinical research, the ASD-Net will follow a translational approach necessary to identify neurobiological pathways of different phenotypes and their appropriate identification and treatment. The work of the ASD-Net will be organized into three clusters concentrating on diagnostics, therapy and health economics. In the diagnostic cluster, data from a large, well-characterized sample (N = 2568) will be analyzed to improve the efficiency of diagnostic procedures. Pattern classification methods (machine learning) will be used to identify algorithms for screening purposes. In a second step, the developed algorithm will be tested in an independent sample. In the therapy cluster, we will unravel how an ASD-specific social skills training with concomitant oxytocin administration can modulate behavior through neurobiological pathways. For the first time, we will characterize long-term effects of a social skills training combined with oxytocin treatment on behavioral and neurobiological phenotypes. Also acute effects of oxytocin will be investigated to delineate general and specific effects of additional oxytocin treatment in order to develop biologically plausible models for symptoms and successful therapeutic interventions in ASD. Finally, in the health economics cluster, we will assess service utilization and ASD-related costs in order to identify potential needs and cost savings specifically tailored to Germany. The ASD-Net has been established as part of the German Research Network for Mental Disorders, funded by the BMBF (German Federal Ministry of Education and Research). Discussion The highly integrated structure of the ASD-Net guarantees sustained collaboration of clinicians and researchers to alleviate individual distress, harm, and social disability of patients with ASD and reduce costs to the German health care system. Trial registration Both clinical trials of the ASD- Net are registered in the German Clinical Trials Register: DRKS00008952 (registered on August 4, 2015) and DRKS00010053 (registered on April 8, 2016)

Mobile Air Quality Studies (MAQS) - an international project

Due to an increasing awareness of the potential hazardousness of air pollutants, new laws, rules and guidelines have recently been implemented globally. In this respect, numerous studies have addressed traffic-related exposure to particulate matter using stationary technology so far. By contrast, only few studies used the advanced technology of mobile exposure analysis. The Mobile Air Quality Study (MAQS) addresses the issue of air pollutant exposure by combining advanced high-granularity spatial-temporal analysis with vehicle-mounted, person-mounted and roadside sensors. The MAQS-platform will be used by international collaborators in order 1) to assess air pollutant exposure in relation to road structure, 2) to assess air pollutant exposure in relation to traffic density, 3) to assess air pollutant exposure in relation to weather conditions, 4) to compare exposure within vehicles between front and back seat (children) positions, and 5) to evaluate "traffic zone"- exposure in relation to non-"traffic zone"-exposure. Primarily, the MAQS-platform will focus on particulate matter. With the establishment of advanced mobile analysis tools, it is planed to extend the analysis to other pollutants including including NO2, SO2, nanoparticles, and ozone

Addiction Research Consortium: Losing and regaining control over drug intake (ReCoDe)—From trajectories to mechanisms and interventions

One of the major risk factors for global death and disability is alcohol, tobacco, and illicit drug use. While there is increasing knowledge with respect to individual factors promoting the initiation and maintenance of substance use disorders (SUDs), disease trajectories involved in losing and regaining control over drug intake (ReCoDe) are still not well described. Our newly formed German Collaborative Research Centre (CRC) on ReCoDe has an interdisciplinary approach funded by the German Research Foundation (DFG) with a 12-year perspective. The main goals of our research consortium are (i) to identify triggers and modifying factors that longitudinally modulate the trajectories of losing and regaining control over drug consumption in real life, (ii) to study underlying behavioral, cognitive, and neurobiological mechanisms, and (iii) to implicate mechanism-based interventions. These goals will be achieved by: (i) using mobile health (m-health) tools to longitudinally monitor the effects of triggers (drug cues, stressors, and priming doses) and modify factors (eg, age, gender, physical activity, and cognitive control) on drug consumption patterns in real-life conditions and in animal models of addiction; (ii) the identification and computational modeling of key mechanisms mediating the effects of such triggers and modifying factors on goal-directed, habitual, and compulsive aspects of behavior from human studies and animal models; and (iii) developing and testing interventions that specifically target the underlying mechanisms for regaining control over drug intake

Randomized controlled phase 2 trial of hydroxychloroquine in childhood interstitial lung disease

Background No results of controlled trials are available for any of the few treatments offered to children with interstitial lung diseases (chILD). We evaluated hydroxychloroquine (HCQ) in a phase 2, prospective, multicentre, 1:1-randomized, double-blind, placebo-controlled, parallel-group/crossover trial. HCQ (START arm) or placebo were given for 4 weeks. Then all subjects received HCQ for another 4 weeks. In the STOP arm subjects already taking HCQ were randomized to 12 weeks of HCQ or placebo (= withdrawal of HCQ). Then all subjects stopped treatment and were observed for another 12 weeks. Results 26 subjects were included in the START arm, 9 in the STOP arm, of these four subjects participated in both arms. The primary endpoint, presence or absence of a response to treatment, assessed as oxygenation (calculated from a change in transcutaneous O 2 -saturation of ≥ 5%, respiratory rate ≥ 20% or level of respiratory support), did not differ between placebo and HCQ groups. Secondary endpoints including change of O 2 -saturation ≥ 3%, health related quality of life, pulmonary function and 6-min-walk-test distance, were not different between groups. Finally combining all placebo and all HCQ treatment periods did not identify significant treatment effects. Overall effect sizes were small. HCQ was well tolerated, adverse events were not different between placebo and HCQ. Conclusions Acknowledging important shortcomings of the study, including a small study population, the treatment duration, lack of outcomes like lung function testing below age of 6 years, the small effect size of HCQ treatment observed requires careful reassessments of prescriptions in everyday practice (EudraCT-Nr.: 2013-003714-40, www.clinicaltrialsregister.eu , registered 02.07.2013)

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Oxalic acid has an additional, detoxifying function in Sclerotinia sclerotiorum pathogenesis.

The mechanism of the diseases caused by the necrotroph plant pathogen Sclerotinia sclerotiorum is not well understood. To investigate the role of oxalic acid during infection high resolution, light-, scanning-, transmission electron microscopy and various histochemical staining methods were used. Our inoculation method allowed us to follow degradation of host plant tissue around single hyphae and to observe the reaction of host cells in direct contact with single invading hyphae. After penetration the outer epidermal cell wall matrix appeared degraded around subcuticular hyphae (12-24 hpi). Calcium oxalate crystals were detected in advanced (36-48 hpi) and late (72 hpi) infection stages, but not in early stages. In early infection stages, surprisingly, no toxic effect of oxalic acid eventually secreted by S. sclerotiorum was observed. As oxalic acid is a common metabolite in plants, we propose that attacked host cells are able to metabolize oxalic acid in the early infection stage and translocate it to their vacuoles where it is stored as calcium oxalate. The effects, observed on healthy tissue upon external application of oxalic acid to non-infected, living tissue and cell wall degradation of dead host cells starting at the inner side of the walls support this idea. The results indicate that oxalic acid concentrations in the early stage of infection stay below the toxic level. In plant and fungi oxalic acid/calcium oxalate plays an important role in calcium regulation. Oxalic acid likely could quench calcium ions released during cell wall breakdown to protect growing hyphae from toxic calcium concentrations in the infection area. As calcium antimonate-precipitates were found in vesicles of young hyphae, we propose that calcium is translocated to the older parts of hyphae and detoxified by building non-toxic, stable oxalate crystals. We propose an infection model where oxalic acid plays a detoxifying role in late infection stages

Infection model illustrating the complex interaction between <i>S. sclerotiorum</i> and its host cells sunflower.

<p>Scheme of two epidermal cells infected by hyphae of <i>S. sclerotiorum</i>. After penetration of the cuticle (c) by appressorial hyphae (ahy), subcuticular hyphae (shy) grow in the outer epidermal wall layer (w) and live on the cell wall matrix (intact wall in dark grey, degraded cell wall matrix in light grey (“w”). Subcuticular hyphae (shy) secrete cell wall lytic enzymes (blue dots) and oxalic acid (red dots) that do not kill the host cells immediately (intact cell compartments in continuous lines; degraded cell compartments in broken lines). While the enzymes degrade the matrix of the host cell walls and set free calcium (green dots), oxalic acid (red dots) is metabolized by the host cells and stored in the host cell vacuoles (v). Calcium is taken up by the growing hyphae in vesicles (vc) and translocated back to the older part (“shy”) to prevent un-physiological high calcium concentrations. Finally, host cells die (broken lines), because the degradation of cell walls advances and the concentration of oxalic acid rise. Oxalic acid (red dots) and also vacuolar enzymes of the host cells are set free and an autolytic degradation start from the inner side of the host cell walls contributing to the development of necrotic tissue. After death of the senescent hyphae (broken lines), calcium is again set free and is reacting with oxalic acid building stable calcium oxalate crystals (yellow) in the necrotic tissue around the functionless appressorial hyphae (ahy) of the infection cushion.</p