Usability inspection for sonification applications

Bonification is the representation of data using mainly non-speech sound for the purpose of communication and interpretation. The process and technique of converting the data into sound is called the sonification technique. One or more techniques might be required by a sonification application. However, sonification techniques are not generally suitable for all kinds of data, and often custom techniques are used - where the design is tailored to the domain and nature of the data as well as the users' required tasks within the application. Therefore, it is important to assure the usability of the technique for the specific domain application being developed. In previously reported research, most designers of sonification applications have needed to develop at least a prototype for user testing. The result are interpreted and analysed to look for potential problems and solutions to improve the design. This dissertation has developed a new systematic usability inspection approach called the Task Interpretation Walkthrough (TIW) for the design of sonification application before they go to the initial development phase. It is hypothesized that designers of sonification applications will be able to detect significantly more important potential usability problems before the implementation phase by analysing the interaction between the user and the application as well as paying attention to the different stages of how the data is transformed into sound. It uses two new models - the Sonification Application (SA) model and the User Interpretation Construction (UIC) model. Four experiments with human subjects were carried out to study the feasibility and effectiveness of Task Interpretation Walkthrough inspection by comparing it against two widely used techniques; Heuristic Evaluation and Cognitive Walkthrough. The sonification designs being inspected were a Mobile Phone Joystick Text-Entry with Sound (Experiments I and II), a Diagnosis Tool for Analysis of The Motion and Usage of a Patient's Arm (Experiment III); and an Audio-Visual Analysis Tool of Cervical Sample Slides (Experiment IV). The participants included sound researchers (Experiment II); and students with a background in music technology and software engineering (Experiments I, III and IV), acting either individually or in 2-person groups. The results have shown that the research hypothesis is supported, where the significantly important usability problems were able to be detected before the implementation phase. From the inspection method comparison study, results showed the Task Interpretation Walkthrough to be more effective than the existing techniques (Heuristic Evaluation and Cognitive Walkthrough)

Abstraction, Visualization, and Evolution of Process Models

The increasing adoption of process orientation in companies and organizations has resulted in large process model collections. Each process model of such a collection may comprise dozens or hundreds of elements and captures various perspectives of a business process, i.e., organizational, functional, control, resource, or data perspective. Domain experts having only limited process modeling knowledge, however, hardly comprehend such large and complex process models. Therefore, they demand for a customized (i.e., personalized) view on business processes enabling them to optimize and evolve process models effectively. This thesis contributes the proView framework to systematically create and update process views (i.e., abstractions) on process models and business processes respectively. More precisely, process views abstract large process models by hiding or combining process information. As a result, they provide an abstracted, but personalized representation of process information to domain experts. In particular, updates of a process view are supported, which are then propagated to the related process model as well as associated process views. Thereby, up-to-dateness and consistency of all process views defined on any process model can be always ensured. Finally, proView preserves the behaviour and correctness of a process model. Process abstractions realized by views are still not sufficient to assist domain experts in comprehending and evolving process models. Thus, additional process visualizations are introduced that provide text-based, form-based, and hierarchical representations of process models. Particularly, these process visualizations allow for view-based process abstractions and updates as well. Finally, process interaction concepts are introduced enabling domain experts to create and evolve process models on touch-enabled devices. This facilitates the documentation of process models in workshops or while interviewing process participants at their workplace. Altogether, proView enables domain experts to interact with large and complex process models as well as to evolve them over time, based on process model abstractions, additional process visualizations, and process interaction concepts. The framework is implemented in a proof-ofconcept prototype and validated through experiments and case studies

Ancestral Sequence Reconstruction: Methods and Applications

A major goal in the study of molecular evolution is to elucidate properties of ancestral proteins and to understand their adaption induced by changes in the environment. Due to the lack of macromolecular fossils, ancestral sequence reconstruction (ASR) is the only alternative to deduce sequences for evolutionary precursors of extant proteins. Within the last years, ancestral proteins were inferred spanning a time-period of more than 3 billion years. Ancestral proteins from eubacteria, archaea, yeast, and vertebrates could be reconstructed. Thus, ASR yielded insights into the early history of life and the evolution of proteins and of macromolecular complexes. Moreover, it turned out that ASR is an effiecient method of protein design, because the reconstructed sequences often possess favorable properties like an increased thermostability. The popularity and efficacy of ASR benefitted from improvements in DNA sequencing technology, the enormous rise of computer power and the refinements of algorithms for sequence and phylogenetic analyses to be seen during the last decades. Thus, elaborated ASR methods are at hand nowadays that can be applied to a variety of evolutionary problems. For an ASR application, the user has however to pick representatives from an overwhelming number of sequences, which is no trivial task. To advance ASR technology and to assist the user, the first part of this thesis focusses on the design of a standardized ASR protocol and the development of a novel filter aimed at facilitating sequence selection. In the second part, ASR is used as a method to elucidate properties of an ancestral enzyme complex and to identify protein-protein interaction hotspots

Proceedings of the 2018 Canadian Society for Mechanical Engineering (CSME) International Congress

Published proceedings of the 2018 Canadian Society for Mechanical Engineering (CSME) International Congress, hosted by York University, 27-30 May 2018

Inhibition of the Hedgehog pathway in combination with cytostatics as potential therapeutic option in Ewing Sarcoma

Ewing Sarkome (EWS) zählen zu den mesenchymalen Tumoren und treten gehäuft bei Kindern und Jugendlichen auf. Patienten mit nicht-metastasiertem EWS, die sich einer radikalen chirurgischen Intervention, Radiotherapie und/oder Chemotherapie unterziehen, zeigen eine durchschnittliche 5-Jahres Überlebensrate von über 70 %, wohingegen metastasierte und rezidivierte EWS deutlich schwerer zu behandeln sind. Einer der vielen Gründe dafür ist die zunehmende Resistenz von rezidivierten EWS gegen Chemotherapeutika. Diese beruht unter anderem darauf, dass ABC Transporter wie PGP oder MRP1, welche die Chemotherapeutika wieder aus der Tumorzelle in den Extrazellularraum befördern, von diesen exprimiert werden. Darüber hinaus wird vom EWS das für den Tumor charakteristische Fusionsprotein EWS-FLI1 exprimiert, welches auch die GLI Proteine im Hedgehog (Hh) Signalweg moduliert. Veränderungen im Hh Signalweg wurden bereits in verschiedenen Tumoren beobachtet und korrelieren mit einer erhöhten Tumorbildung und Progression. Da der Hh Signalweg direkt die Expression von ABC Transportern beeinflusst, wurde in dieser Arbeit die Inhibition der GLI Proteine als mögliche zusätzliche Therapieoption zur Unterdrückung der Chemoresistenz getestet. Dafür wurden drei EWS Zelllinien mit den GLI Inhibitoren GANT61 und ATO, sowie den bereits etablierten Chemotherapeutika Etoposid und Doxorubicin behandelt und ihre Viabilität, Koloniebildungsfähigkeit, Wachstum in 3D Kulturen und Induktion von Zelltod mittels MTS Assay, Koloniebildungs-Assay, 3D Spheroid Assay, Durchflusszytometrie und Western Blot getestet. ATO, Etoposid und Doxorubicin reduzierten die Viabilität signifikant und selektiv in allen drei EWS Zelllinien im Vergleich zu mesenchymalen Stammzellen (MSC). Dahingegen war GANT61 weniger effizient in zwei der drei EWS Zelllinien und vor allem nicht selektiv gegenüber MSC. Zelltod konnte durch ATO, Etoposid und Doxorubicin in allen EWS Zelllinien, nicht aber in MSC induziert werden. Dieser Effekt wurde mit der Kombination von ATO und Etoposid noch einmal potenziert. Die Kombination von ATO und Doxorubicin reduzierte die Viabilität ebenfalls signifikant, verglichen mit der Einzelgabe. Eine dreifache Kombination aus ATO, Etoposid und Doxorubicin zeigte jedoch keinen zusätzlichen Nutzen im Vergleich zu den Zweifach-Kombinationen. Die bisherigen Ergebnisse deuten darauf hin, dass ATO zur Erhöhung der Überlebensraten von EWS Patienten und zur Reduzierung von Resistenzen gegen Chemotherapeutika in aggressiven EWS beitragen kann. Durch die reduzierte Dosis der kombinierten Substanzen können Nebenwirkungen der Chemotherapeutika vermindert werden. Vor einem potenziellen klinischen Einsatz werden allerdings weitere Informationen über die detaillierten Wirkmechanismen in EWS benötigt.Ewing sarcoma (EWS) are mesenchymal tumours usually occurring in children and adolescents. Currently, patients with non-metastatic EWS show 5-year survival rates above 70 % when treated radically with surgery, chemotherapy and radiotherapy, whereas relapsed or metastasised EWS are more difficult to treat. One of many reasons is the increasing drug resistance in relapsed EWS including the expression of ABC transporters such as PGP or MRP1 which transport cytostatic drugs back through the cell membrane into the extracellular matrix. Furthermore, EWS express the characteristic EWS-FLI1 fusion protein which also modulates the GLI proteins in the Hedgehog (Hh) pathway. Aberrant Hh-signalling has been observed in several malignancies including EWS and correlates with cancer formation and progression. As the Hh pathway directly targets expression of ABC transporter proteins, GLI inhibition as additional therapeutic option to overcome multi drug resistance was investigated. In the present study viability, colony formation, growth of 3D cultures and induction of cell death was analysed in three EWS cell lines treated with the GLI inhibitors GANT61 and ATO as well as the established cytostatics etoposide and doxorubicin using MTS assay, clonogenic assay, 3D spheroid assay, flow cytometry and western blot. ATO, etoposide and doxorubicin reduced viability significantly and selectively in all three EWS cell lines in comparison to mesenchymal stem cells (MSC). On the other hand, GANT61 was less efficient in two of three EWS cell lines and particularly not selective compared to MSC. Cell death was induced by ATO, etoposide and doxorubicin in all three EWS cell lines, but not MSC. The combination of ATO and etoposide potentiated this effect. The combined application of ATO and doxorubicin also significantly compromised viability compared to individual treatment. However, a triple combination of ATO with both cytostatics did not compromise cells more than the double combinations. The present results indicate that ATO is effective in EWS. Therefore, ATO may contribute to increased survival rates of patients with EWS and especially reduce resistance of aggressive EWS against chemotherapeutics. Furthermore, as doses for drugs can be reduced in combined treatment, adverse effects of chemotherapy may be diminished. However, further evaluation of the detailed inhibitory mechanisms in EWS is needed before transferring this approach to the clinic

SPICA:revealing the hearts of galaxies and forming planetary systems : approach and US contributions

How did the diversity of galaxies we see in the modern Universe come to be? When and where did stars within them forge the heavy elements that give rise to the complex chemistry of life? How do planetary systems, the Universe's home for life, emerge from interstellar material? Answering these questions requires techniques that penetrate dust to reveal the detailed contents and processes in obscured regions. The ESA-JAXA Space Infrared Telescope for Cosmology and Astrophysics (SPICA) mission is designed for this, with a focus on sensitive spectroscopy in the 12 to 230 micron range. SPICA offers massive sensitivity improvements with its 2.5-meter primary mirror actively cooled to below 8 K. SPICA one of 3 candidates for the ESA's Cosmic Visions M5 mission, and JAXA has is committed to their portion of the collaboration. ESA will provide the silicon-carbide telescope, science instrument assembly, satellite integration and testing, and the spacecraft bus. JAXA will provide the passive and active cooling system (supporting the

The Apertif Surveys:The First Six Months

Apertif is a new phased-array feed for the Westerbork Synthesis Radio Telescope (WSRT), greatly increasing its field of view and turning it into a natural survey instrument. In July 2019, the Apertif legacy surveys commenced; these are a time-domain survey and a two-tiered imaging survey, with a shallow and medium-deep component. The time-domain survey searches for new (millisecond) pulsars and fast radio bursts (FRBs). The imaging surveys provide neutral hydrogen (HI), radio continuum and polarization data products. With a bandwidth of 300 MHz, Apertif can detect HI out to a redshift of 0.26. The key science goals to be accomplished by Apertif include localization of FRBs (including real-time public alerts), the role of environment and interaction on galaxy properties and gas removal, finding the smallest galaxies, connecting cold gas to AGN, understanding the faint radio population, and studying magnetic fields in galaxies. After a proprietary period, survey data products will be publicly available through the Apertif Long Term Archive (ALTA, https://alta.astron.nl). I will review the progress of the surveys and present the first results from the Apertif surveys, including highlighting the currently available public data