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    STonKGs: A Sophisticated Transformer Trained on Biomedical Text and Knowledge Graphs

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    MOTIVATION The majority of biomedical knowledge is stored in structured databases or as unstructured text in scientific publications. This vast amount of information has led to numerous machine learning-based biological applications using either text through natural language processing (NLP) or structured data through knowledge graph embedding models (KGEMs). However, representations based on a single modality are inherently limited. RESULTS To generate better representations of biological knowledge, we propose STonKGs, a Sophisticated Transformer trained on biomedical text and Knowledge Graphs (KGs). This multimodal Transformer uses combined input sequences of structured information from KGs and unstructured text data from biomedical literature to learn joint representations in a shared embedding space. First, we pre-trained STonKGs on a knowledge base assembled by the Integrated Network and Dynamical Reasoning Assembler (INDRA) consisting of millions of text-triple pairs extracted from biomedical literature by multiple NLP systems. Then, we benchmarked STonKGs against three baseline models trained on either one of the modalities (i.e., text or KG) across eight different classification tasks, each corresponding to a different biological application. Our results demonstrate that STonKGs outperforms both baselines, especially on the more challenging tasks with respect to the number of classes, improving upon the F1-score of the best baseline by up to 0.084 (i.e., from 0.881 to 0.965). Finally, our pre-trained model as well as the model architecture can be adapted to various other transfer learning applications. AVAILABILITY We make the source code and the Python package of STonKGs available at GitHub (https://github.com/stonkgs/stonkgs) and PyPI (https://pypi.org/project/stonkgs/). The pre-trained STonKGs models and the task-specific classification models are respectively available at https://huggingface.co/stonkgs/stonkgs-150k and https://zenodo.org/communities/stonkgs. SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online

    Biomarkers for drug development in propionic and methylmalonic acidemias

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    There is an unmet need for the development and validation of biomarkers and surrogate endpoints for clinical trials in propionic acidemia (PA) and methylmalonic acidemia (MMA). This review examines the pathophysiology and clinical consequences of PA and MMA that could form the basis for potential biomarkers and surrogate endpoints. Changes in primary metabolites such as methylcitric acid (MCA), MCA:citric acid ratio, oxidation of 13C-propionate (exhaled 13CO2), and propionylcarnitine (C3) have demonstrated clinical relevance in patients with PA or MMA. Methylmalonic acid, another primary metabolite, is a potential biomarker, but only in patients with MMA. Other potential biomarkers in patients with either PA and MMA include secondary metabolites, such as ammonium, or the mitochondrial disease marker, fibroblast growth factor 21. Additional research is needed to validate these biomarkers as surrogate endpoints, and to determine whether other metabolites or markers of organ damage could also be useful biomarkers for clinical trials of investigational drug treatments in patients with PA or MMA. This review examines the evidence supporting a variety of possible biomarkers for drug development in propionic and methylmalonic acidemias

    Agile IT Performance Measurement

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    Während im IT-Projektmanagement agile Methoden seit vielen Jahren in der Praxis Zuspruch finden, werden im IT-Controlling überwiegend noch klassische Methoden eingesetzt. Der Beitrag untersucht die Fragestellung, ob und wie die im IT-Controlling eingesetzten Methoden auch agilen Paradigmen folgen und Methoden des agilen IT-Projektmanagements adaptiert werden können.While agile methods have been popular in practice in IT project management for many years, classic methods are still predominantly used in IT performance measurement. The article examines the question of whether and how the methods used in IT performance measurement also follow agile paradigms and agile IT project management methods can be adapted

    Highly potent inhibitors of cathepsin K with a differently positioned cyanohydrazide warhead: structural analysis of binding mode to mature and zymogen-like enzymes

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    Cathepsin K (CatK) is a target for the treatment of osteoporosis, arthritis, and bone metastasis. Peptidomimetics with a cyanohydrazide warhead represent a new class of highly potent CatK inhibitors; however, their binding mechanism is unknown. We investigated two model cyanohydrazide inhibitors with differently positioned warheads: an azadipeptide nitrile Gü1303 and a 3-cyano-3-aza-β-amino acid Gü2602. Crystal structures of their covalent complexes were determined with mature CatK as well as a zymogen-like activation intermediate of CatK. Binding mode analysis, together with quantum chemical calculations, revealed that the extraordinary picomolar potency of Gü2602 is entropically favoured by its conformational flexibility at the nonprimed-primed subsites boundary. Furthermore, we demonstrated by live cell imaging that cyanohydrazides effectively target mature CatK in osteosarcoma cells. Cyanohydrazides also suppressed the maturation of CatK by inhibiting the autoactivation of the CatK zymogen. Our results provide structural insights for the rational design of cyanohydrazide inhibitors of CatK as potential drugs

    Elements of XR Prototyping: Characterizing the Role and Use of Prototypes in Augmented and Virtual Reality Design

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    Current research in augmented, virtual, and mixed reality (XR) reveals a lack of tool support for designing and, in particular, prototyping XR applications. While recent tools research is often motivated by studying the requirements of non-technical designers and end-user developers, the perspective of industry practitioners is less well understood. In an interview study with 17 practitioners from different industry sectors working on professional XR projects, we establish the design practices in industry, from early project stages to the final product. To better understand XR design challenges, we characterize the different methods and tools used for prototyping and describe the role and use of key prototypes in the different projects. We extract common elements of XR prototyping, elaborating on the tools and materials used for prototyping and establishing different views on the notion of fidelity. Finally, we highlight key issues for future XR tools research

    P45 - Koaxial elektrogesponnene Fasern mit flüssigkristallinem Kern zur optischen Detektion von Amphetamin in der Gasphase

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    Sensoren können verschiedene Aufgaben erfüllen, wie beispielsweise die Optimierung von Prozessen, die Interaktion zwischen Geräten oder die Verbesserung der zivilen Sicherheit. [1–3] Ihr Bedarf für die Industrie oder den Alltag wächst seit Jahren stetig. Besonders mobile Gassensoren sind von großem Interesse. Jedoch ist ihre Anwendung meist durch ihre integrierte Batterie begrenzt. Gassensoren ohne oder mit einem nur sehr geringen Energieverbrauch stehen daher im Interesse bei neuen Anwendungsgebieten, beispielsweise im Brandschutz oder in der Textilindustrie. [4,5] Die Sensoren könnten zum Beispiel in die Textilien einer persönlichen Schutzausrüstung eingearbeitet werden und durch einen Farbumschlag die Anwesenheit eines Gases oder die Überschreitung des Grenzwertes toxischer Substanzen anzeigen

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