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N-of-1 trials are the gold standard study design to evaluate individual treatment effects and derive personalized treatment strategies. Digital tools have the potential to initiate a new era of N-of-1 trials in terms of scale and scope, but fully functional platforms are not yet available.
Here, we present the open source StudyU platform, which includes the StudyU Designer and StudyU app.
With the StudyU Designer, scientists are given a collaborative web application to digitally specify, publish, and conduct N-of-1 trials.
The StudyU app is a smartphone app with innovative user-centric elements for participants to partake in trials published through the StudyU Designer to assess the effects of different interventions on their health.
Thereby, the StudyU platform allows clinicians and researchers worldwide to easily design and conduct digital N-of-1 trials in a safe manner.
We envision that StudyU can change the landscape of personalized treatments both for patients and healthy individuals, democratize and personalize evidence generation for self-optimization and medicine, and can be integrated in clinical practice.
RHEEMix in the data jungle
(2020)
Data analytics are moving beyond the limits of a single platform. In this paper, we present the cost-based optimizer of Rheem, an open-source cross-platform system that copes with these new requirements. The optimizer allocates the subtasks of data analytic tasks to the most suitable platforms. Our main contributions are: (i) a mechanism based on graph transformations to explore alternative execution strategies; (ii) a novel graph-based approach to determine efficient data movement plans among subtasks and platforms; and (iii) an efficient plan enumeration algorithm, based on a novel enumeration algebra. We extensively evaluate our optimizer under diverse real tasks. We show that our optimizer can perform tasks more than one order of magnitude faster when using multiple platforms than when using a single platform.
Wo programmiert wird, da passieren Fehler. Um das Debugging, also die Suche sowie die Behebung von Fehlern in Quellcode, stärker explizit zu adressieren, verfolgt die vorliegende Arbeit das Ziel, entlang einer prototypischen Lernumgebung sowohl ein systematisches Vorgehen während des Debuggings zu vermitteln als auch Gestaltungsfolgerungen für ebensolche Lernumgebungen zu identifizieren. Dazu wird die folgende Forschungsfrage gestellt: Wie verhalten sich die Lernenden während des kurzzeitigen Gebrauchs einer Lernumgebung nach dem Cognitive Apprenticeship-Ansatz mit dem Ziel der expliziten Vermittlung eines systematischen Debuggingvorgehens und welche Eindrücke entstehen während der Bearbeitung?
Zur Beantwortung dieser Forschungsfrage wurde orientierend an literaturbasierten Implikationen für die Vermittlung von Debugging und (medien-)didaktischen Gestaltungsaspekten eine prototypische Lernumgebung entwickelt und im Rahmen einer qualitativen Nutzerstudie mit Bachelorstudierenden informatischer Studiengänge erprobt. Hierbei wurden zum einen anwendungsbezogene Verbesserungspotenziale identifiziert. Zum anderen zeigte sich insbesondere gegenüber der Systematisierung des Debuggingprozesses innerhalb der Aufgabenbearbeitung eine positive Resonanz. Eine Untersuchung, inwieweit sich die Nutzung der Lernumgebung längerfristig auf das Verhalten von Personen und ihre Vorgehensweisen während des Debuggings auswirkt, könnte Gegenstand kommender Arbeiten sein.
Concepts and techniques for 3D-embedded treemaps and their application to software visualization
(2024)
This thesis addresses concepts and techniques for interactive visualization of hierarchical data using treemaps. It explores (1) how treemaps can be embedded in 3D space to improve their information content and expressiveness, (2) how the readability of treemaps can be improved using level-of-detail and degree-of-interest techniques, and (3) how to design and implement a software framework for the real-time web-based rendering of treemaps embedded in 3D. With a particular emphasis on their application, use cases from software analytics are taken to test and evaluate the presented concepts and techniques.
Concerning the first challenge, this thesis shows that a 3D attribute space offers enhanced possibilities for the visual mapping of data compared to classical 2D treemaps. In particular, embedding in 3D allows for improved implementation of visual variables (e.g., by sketchiness and color weaving), provision of new visual variables (e.g., by physically based materials and in situ templates), and integration of visual metaphors (e.g., by reference surfaces and renderings of natural phenomena) into the three-dimensional representation of treemaps.
For the second challenge—the readability of an information visualization—the work shows that the generally higher visual clutter and increased cognitive load typically associated with three-dimensional information representations can be kept low in treemap-based representations of both small and large hierarchical datasets. By introducing an adaptive level-of-detail technique, we cannot only declutter the visualization results, thereby reducing cognitive load and mitigating occlusion problems, but also summarize and highlight relevant data. Furthermore, this approach facilitates automatic labeling, supports the emphasis on data outliers, and allows visual variables to be adjusted via degree-of-interest measures.
The third challenge is addressed by developing a real-time rendering framework with WebGL and accumulative multi-frame rendering. The framework removes hardware constraints and graphics API requirements, reduces interaction response times, and simplifies high-quality rendering. At the same time, the implementation effort for a web-based deployment of treemaps is kept reasonable.
The presented visualization concepts and techniques are applied and evaluated for use cases in software analysis. In this domain, data about software systems, especially about the state and evolution of the source code, does not have a descriptive appearance or natural geometric mapping, making information visualization a key technology here. In particular, software source code can be visualized with treemap-based approaches because of its inherently hierarchical structure. With treemaps embedded in 3D, we can create interactive software maps that visually map, software metrics, software developer activities, or information about the evolution of software systems alongside their hierarchical module structure.
Discussions on remaining challenges and opportunities for future research for 3D-embedded treemaps and their applications conclude the thesis.
Die fortschreitende Digitalisierung durchzieht immer mehr Lebensbereiche und führt zu immer komplexeren sozio-technischen Systemen. Obwohl diese Systeme zur Lebenserleichterung entwickelt werden, können auch unerwünschte Nebeneffekte entstehen. Ein solcher Nebeneffekt könnte z.B. die Datennutzung aus Fitness-Apps für nachteilige Versicherungsentscheidungen sein. Diese Nebeneffekte manifestieren sich auf allen Ebenen zwischen Individuum und Gesellschaft. Systeme mit zuvor unerwarteten Nebeneffekten können zu sinkender Akzeptanz oder einem Verlust von Vertrauen führen. Da solche Nebeneffekte oft erst im Gebrauch in Erscheinung treten, bedarf es einer besonderen Betrachtung bereits im Konstruktionsprozess. Mit dieser Arbeit soll ein Beitrag geleistet werden, um den Konstruktionsprozess um ein geeignetes Hilfsmittel zur systematischen Reflexion zu ergänzen.
In vorliegender Arbeit wurde ein Analysetool zur Identifikation und Analyse komplexer Interaktionssituationen in Software-Entwicklungsprojekten entwickelt. Komplexe Interaktionssituationen sind von hoher Dynamik geprägt, aus der eine Unvorhersehbarkeit der Ursache-Wirkungs-Beziehungen folgt. Hierdurch können die Akteur*innen die Auswirkungen der eigenen Handlungen nicht mehr überblicken, sondern lediglich im Nachhinein rekonstruieren. Hieraus können sich fehlerhafte Interaktionsverläufe auf vielfältigen Ebenen ergeben und oben genannte Nebeneffekte entstehen. Das Analysetool unterstützt die Konstrukteur*innen in jeder Phase der Entwicklung durch eine angeleitete Reflexion, um potenziell komplexe Interaktionssituationen zu antizipieren und ihnen durch Analyse der möglichen Ursachen der Komplexitätswahrnehmung zu begegnen.
Ausgehend von der Definition für Interaktionskomplexität wurden Item-Indikatoren zur Erfassung komplexer Interaktionssituationen entwickelt, die dann anhand von geeigneten Kriterien für Komplexität analysiert werden. Das Analysetool ist als „Do-It-Yourself“ Fragebogen mit eigenständiger Auswertung aufgebaut. Die Genese des Fragebogens und die Ergebnisse der durchgeführten Evaluation an fünf Softwarentwickler*innen werden dargestellt. Es konnte festgestellt werden, dass das Analysetool bei den Befragten als anwendbar, effektiv und hilfreich wahrgenommen wurde und damit eine hohe Akzeptanz bei der Zielgruppe genießt. Dieser Befund unterstützt die gute Einbindung des Analysetools in den Software-Entwicklungsprozess.
Omics and male infertility
(2022)
Male infertility is a multifaceted disorder affecting approximately 50% of male partners in infertile couples.
Over the years, male infertility has been diagnosed mainly through semen analysis, hormone evaluations, medical records and physical examinations, which of course are fundamental, but yet inefficient, because 30% of male infertility cases remain idiopathic. This dilemmatic status of the unknown needs to be addressed with more sophisticated and result-driven technologies and/or techniques.
Genetic alterations have been linked with male infertility, thereby unveiling the practicality of investigating this disorder from the "omics" perspective.
Omics aims at analyzing the structure and functions of a whole constituent of a given biological function at different levels, including the molecular gene level (genomics), transcript level (transcriptomics), protein level (proteomics) and metabolites level (metabolomics). In the current study, an overview of the four branches of omics and their roles in male infertility are briefly discussed; the potential usefulness of assessing transcriptomic data to understand this pathology is also elucidated.
After assessing the publicly obtainable transcriptomic data for datasets on male infertility, a total of 1385 datasets were retrieved, of which 10 datasets met the inclusion criteria and were used for further analysis.
These datasets were classified into groups according to the disease or cause of male infertility.
The groups include non-obstructive azoospermia (NOA), obstructive azoospermia (OA), non-obstructive and obstructive azoospermia (NOA and OA), spermatogenic dysfunction, sperm dysfunction, and Y chromosome microdeletion.
Findings revealed that 8 genes (LDHC, PDHA2, TNP1, TNP2, ODF1, ODF2, SPINK2, PCDHB3) were commonly differentially expressed between all disease groups.
Likewise, 56 genes were common between NOA versus NOA and OA (ADAD1, BANF2, BCL2L14, C12orf50, C20orf173, C22orf23, C6orf99, C9orf131, C9orf24, CABS1, CAPZA3, CCDC187, CCDC54, CDKN3, CEP170, CFAP206, CRISP2, CT83, CXorf65, FAM209A, FAM71F1, FAM81B, GALNTL5, GTSF1, H1FNT, HEMGN, HMGB4, KIF2B, LDHC, LOC441601, LYZL2, ODF1, ODF2, PCDHB3, PDHA2, PGK2, PIH1D2, PLCZ1, PROCA1, RIMBP3, ROPN1L, SHCBP1L, SMCP, SPATA16, SPATA19, SPINK2, TEX33, TKTL2, TMCO2, TMCO5A, TNP1, TNP2, TSPAN16, TSSK1B, TTLL2, UBQLN3).
These genes, particularly the above-mentioned 8 genes, are involved in diverse biological processes such as germ cell development, spermatid development, spermatid differentiation, regulation of proteolysis, spermatogenesis and metabolic processes.
Owing to the stage-specific expression of these genes, any mal-expression can ultimately lead to male infertility.
Therefore, currently available data on all branches of omics relating to male fertility can be used to identify biomarkers for diagnosing male infertility, which can potentially help in unravelling some idiopathic cases.
Modern data analysis tasks often involve control flow statements, such as the iterations in PageRank and K-means. To achieve scalability, developers usually implement these tasks in distributed dataflow systems, such as Spark and Flink. Designers of such systems have to choose between providing imperative or functional control flow constructs to users. Imperative constructs are easier to use, but functional constructs are easier to compile to an efficient dataflow job. We propose Mitos, a system where control flow is both easy to use and efficient. Mitos relies on an intermediate representation based on the static single assignment form. This allows us to abstract away from specific control flow constructs and treat any imperative control flow uniformly both when building the dataflow job and when coordinating the distributed execution.
Stem cells are capable of sensing and processing environmental inputs, converting this information to output a specific cell lineage through signaling cascades. Despite the combinatorial nature of mechanical, thermal, and biochemical signals, these stimuli have typically been decoupled and applied independently, requiring continuous regulation by controlling units. We employ a programmable polymer actuator sheet to autonomously synchronize thermal and mechanical signals applied to mesenchymal stem cells (MSC5). Using a grid on its underside, the shape change of polymer sheet, as well as cell morphology, calcium (Ca2+) influx, and focal adhesion assembly, could be visualized and quantified. This paper gives compelling evidence that the temperature sensing and mechanosensing of MSC5 are interconnected via intracellular Ca2+. Up-regulated Ca2+ levels lead to a remarkable alteration of histone H3K9 acetylation and activation of osteogenic related genes. The interplay of physical, thermal, and biochemical signaling was utilized to accelerate the cell differentiation toward osteogenic lineage. The approach of programmable bioinstructivity provides a fundamental principle for functional biomaterials exhibiting multifaceted stimuli on differentiation programs. Technological impact is expected in the tissue engineering of periosteum for treating bone defects.
Stem cells are capable of sensing and processing environmental inputs, converting this information to output a specific cell lineage through signaling cascades. Despite the combinatorial nature of mechanical, thermal, and biochemical signals, these stimuli have typically been decoupled and applied independently, requiring continuous regulation by controlling units. We employ a programmable polymer actuator sheet to autonomously synchronize thermal and mechanical signals applied to mesenchymal stem cells (MSC5). Using a grid on its underside, the shape change of polymer sheet, as well as cell morphology, calcium (Ca2+) influx, and focal adhesion assembly, could be visualized and quantified. This paper gives compelling evidence that the temperature sensing and mechanosensing of MSC5 are interconnected via intracellular Ca2+. Up-regulated Ca2+ levels lead to a remarkable alteration of histone H3K9 acetylation and activation of osteogenic related genes. The interplay of physical, thermal, and biochemical signaling was utilized to accelerate the cell differentiation toward osteogenic lineage. The approach of programmable bioinstructivity provides a fundamental principle for functional biomaterials exhibiting multifaceted stimuli on differentiation programs. Technological impact is expected in the tissue engineering of periosteum for treating bone defects.