Verbesserung der Qualität von historischen Filmen

Historische Filme stellen einen wichtigen Baustein für die Erhaltung des kulturellen Erbes dar. Durch eine Digitalisierung können diese für die Zukunft erhalten werden, ohne dass Filme durch Materialermüdung der Filmrollen bzw. Bänder Schaden nehmen. Viele der historischen Aufnahmen sind durch Abspielen oder Lagerung bereits deutlich beschädigt. In diesem Bericht werden Algorithmen zur Erkennung und Behebung solcher Fehler in historischen Schwarzweißfilmen vorgestellt. Dabei handelt es sich um die Erkennung und Beseitigung von horizontalen Störlinien, um die Helligkeits- und Kontrastkorrektur sowohl bei starken Helligkeitsschwankungen als auch bei überdunkelten oder überhellten Sequenzen, sowie um die Entfernung von Verwackelungen bei Kameraeinstellungen

Standardized metadata collection to reinforce collaboration in Collaborative Research Centers

We present our approach for research (meta)data exchange and interconnection of scientists in medium-scale academic projects such as medical collaborative research centers (CRCs). Our webbased tool, fredato, connects established services, which we configure to a custom-tailored software bundle to match the needs of researchers. To improve collaboration, we implemented a metadata acquisition component and search function to complement the existing data management and sharing. More specifically, we enhance three points: 1. Relevant projects need to be findable to re-use data or results, avoid redundant work and improve communication among crc members. 2. The scientists also process sensitive human data for which a privacy-protected, secure exchange is critical. 3. A self-explanatory user interface is required for increased user acceptance. The main feature we present is the handling of metadata in our web application without overwhelming users through extensive and generic forms. We use flexible JSON schemas to precisely target scientists' needs of documentation and enrich them with only ontology components relevant to their use cases. The schemas are stored distributedly as datasets themselves, and automatically converted to modern web forms. Besides custom, domain-specific forms we use this editor for the addition of common metadata schemas (e.g. DataCite). We use the continuous integration capabilities of a connected Gitlab to run data-driven scripts. This includes indexing of all metadata, which makes them searchable in a structured way. Users are provided with contact information for matches and can ask to share data and results. Because project owners decide with whom to share and because datasets and metadata are bundled together, the complete dataset is always accessible (e.g. for publication at a third party repository) and full control retained by data owners. By adding this component to our tool, we provide simple, secure and searchable means for improving collaboration in the context of CRCs

VarFish: comprehensive DNA variant analysis for diagnostics and research

VarFish is a user-friendly web application for the quality control, filtering, prioritization, analysis, and user-based annotation of DNA variant data with a focus on rare disease genetics. It is capable of processing variant call files with single or multiple samples. The variants are automatically annotated with population frequencies, molecular impact, and presence in databases such as ClinVar. Further, it provides support for pathogenicity scores including CADD, MutationTaster, and phenotypic similarity scores. Users can filter variants based on these annotations and presumed inheritance pattern and sort the results by these scores. Variants passing the filter are listed with their annotations and many useful link-outs to genome browsers, other gene/variant data portals, and external tools for variant assessment. VarFish allows users to create their own annotations including support for variant assessment following ACMG-AMP guidelines. In close collaboration with medical practitioners, VarFish was designed for variant analysis and prioritization in diagnostic and research settings as described in the software's extensive manual. The user interface has been optimized for supporting these protocols. Users can install VarFish on their own in-house servers where it provides additional lab notebook features for collaborative analysis and allows re-analysis of cases, e.g. after update of genotype or phenotype databases

The challenges of research data management in cardiovascular science: a DGK and DZHK position paper-executive summary

The sharing and documentation of cardiovascular research data are essential for efficient use and reuse of data, thereby aiding scientific transparency, accelerating the progress of cardiovascular research and healthcare, and contributing to the reproducibility of research results. However, challenges remain. This position paper, written on behalf of and approved by the German Cardiac Society and German Centre for Cardiovascular Research, summarizes our current understanding of the challenges in cardiovascular research data management (RDM). These challenges include lack of time, awareness, incentives, and funding for implementing effective RDM; lack of standardization in RDM processes; a need to better identify meaningful and actionable data among the increasing volume and complexity of data being acquired; and a lack of understanding of the legal aspects of data sharing. While several tools exist to increase the degree to which data are findable, accessible, interoperable, and reusable (FAIR), more work is needed to lower the threshold for effective RDM not just in cardiovascular research but in all biomedical research, with data sharing and reuse being factored in at every stage of the scientific process. A culture of open science with FAIR research data should be fostered through education and training of early-career and established research professionals. Ultimately, FAIR RDM requires permanent, long-term effort at all levels. If outcomes can be shown to be superior and to promote better (and better value) science, modern RDM will make a positive difference to cardiovascular science and practice. The full position paper is available in the supplementary materials

Electrostatic Effects in the Folding of the SH3 Domain of the c-Src Tyrosine Kinase: pH-Dependence in 3D-Domain Swapping and Amyloid Formation

The SH3 domain of the c-Src tyrosine kinase (c-Src-SH3) aggregates to form intertwined dimers and amyloid fibrils at mild acid pHs. In this work, we show that a single mutation of residue Gln128 of this SH3 domain has a significant effect on: (i) its thermal stability; and (ii) its propensity to form amyloid fibrils. The Gln128Glu mutant forms amyloid fibrils at neutral pH but not at mild acid pH, while Gln128Lys and Gln128Arg mutants do not form these aggregates under any of the conditions assayed. We have also solved the crystallographic structures of the wild-type (WT) and Gln128Glu, Gln128Lys and Gln128Arg mutants from crystals obtained at different pHs. At pH 5.0, crystals belong to the hexagonal space group P6522 and the asymmetric unit is formed by one chain of the protomer of the c-Src-SH3 domain in an open conformation. At pH 7.0, crystals belong to the orthorhombic space group P212121, with two molecules at the asymmetric unit showing the characteristic fold of the SH3 domain. Analysis of these crystallographic structures shows that the residue at position 128 is connected to Glu106 at the diverging β-turn through a cluster of water molecules. Changes in this hydrogen-bond network lead to the displacement of the c-Src-SH3 distal loop, resulting also in conformational changes of Leu100 that might be related to the binding of proline rich motifs. Our findings show that electrostatic interactions and solvation of residues close to the folding nucleation site of the c-Src-SH3 domain might play an important role during the folding reaction and the amyloid fibril formation.This research was funded by the Spanish Ministry of Science and Innovation and Ministry of Economy and Competitiveness and FEDER (EU): BIO2009-13261-C02-01/02 (ACA); BIO2012-39922-C02-01/02 (ACA); CTQ2013-4493 (JLN) and CSD2008-00005 (JLN); Andalusian Regional Government (Spain) and FEDER (EU): P09-CVI-5063 (ACA); and Valentian Regional Government (Spain) and FEDER (EU): Prometeo 2013/018 (JLN). Data collection was supported by European Synchrotron Radiation Facility (ESRF), Grenoble, France: BAG proposals MX-1406 (ACA) and MX-1541 (ACA); and ALBA (Barcelona, Spain) proposals 2012010072 (ACA) and 2012100378 (ACA)

Multisite de novo mutations in human offspring after paternal exposure to ionizing radiation

Contains fulltext : 196641.pdf (publisher's version ) (Open Access