5,418 research outputs found

    Towards A Practical High-Assurance Systems Programming Language

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    Writing correct and performant low-level systems code is a notoriously demanding job, even for experienced developers. To make the matter worse, formally reasoning about their correctness properties introduces yet another level of complexity to the task. It requires considerable expertise in both systems programming and formal verification. The development can be extremely costly due to the sheer complexity of the systems and the nuances in them, if not assisted with appropriate tools that provide abstraction and automation. Cogent is designed to alleviate the burden on developers when writing and verifying systems code. It is a high-level functional language with a certifying compiler, which automatically proves the correctness of the compiled code and also provides a purely functional abstraction of the low-level program to the developer. Equational reasoning techniques can then be used to prove functional correctness properties of the program on top of this abstract semantics, which is notably less laborious than directly verifying the C code. To make Cogent a more approachable and effective tool for developing real-world systems, we further strengthen the framework by extending the core language and its ecosystem. Specifically, we enrich the language to allow users to control the memory representation of algebraic data types, while retaining the automatic proof with a data layout refinement calculus. We repurpose existing tools in a novel way and develop an intuitive foreign function interface, which provides users a seamless experience when using Cogent in conjunction with native C. We augment the Cogent ecosystem with a property-based testing framework, which helps developers better understand the impact formal verification has on their programs and enables a progressive approach to producing high-assurance systems. Finally we explore refinement type systems, which we plan to incorporate into Cogent for more expressiveness and better integration of systems programmers with the verification process

    Using machine learning to predict pathogenicity of genomic variants throughout the human genome

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    Geschätzt mehr als 6.000 Erkrankungen werden durch Veränderungen im Genom verursacht. Ursachen gibt es viele: Eine genomische Variante kann die Translation eines Proteins stoppen, die Genregulation stören oder das Spleißen der mRNA in eine andere Isoform begünstigen. All diese Prozesse müssen überprüft werden, um die zum beschriebenen Phänotyp passende Variante zu ermitteln. Eine Automatisierung dieses Prozesses sind Varianteneffektmodelle. Mittels maschinellem Lernen und Annotationen aus verschiedenen Quellen bewerten diese Modelle genomische Varianten hinsichtlich ihrer Pathogenität. Die Entwicklung eines Varianteneffektmodells erfordert eine Reihe von Schritten: Annotation der Trainingsdaten, Auswahl von Features, Training verschiedener Modelle und Selektion eines Modells. Hier präsentiere ich ein allgemeines Workflow dieses Prozesses. Dieses ermöglicht es den Prozess zu konfigurieren, Modellmerkmale zu bearbeiten, und verschiedene Annotationen zu testen. Der Workflow umfasst außerdem die Optimierung von Hyperparametern, Validierung und letztlich die Anwendung des Modells durch genomweites Berechnen von Varianten-Scores. Der Workflow wird in der Entwicklung von Combined Annotation Dependent Depletion (CADD), einem Varianteneffektmodell zur genomweiten Bewertung von SNVs und InDels, verwendet. Durch Etablierung des ersten Varianteneffektmodells für das humane Referenzgenome GRCh38 demonstriere ich die gewonnenen Möglichkeiten Annotationen aufzugreifen und neue Modelle zu trainieren. Außerdem zeige ich, wie Deep-Learning-Scores als Feature in einem CADD-Modell die Vorhersage von RNA-Spleißing verbessern. Außerdem werden Varianteneffektmodelle aufgrund eines neuen, auf Allelhäufigkeit basierten, Trainingsdatensatz entwickelt. Diese Ergebnisse zeigen, dass der entwickelte Workflow eine skalierbare und flexible Möglichkeit ist, um Varianteneffektmodelle zu entwickeln. Alle entstandenen Scores sind unter cadd.gs.washington.edu und cadd.bihealth.org frei verfügbar.More than 6,000 diseases are estimated to be caused by genomic variants. This can happen in many possible ways: a variant may stop the translation of a protein, interfere with gene regulation, or alter splicing of the transcribed mRNA into an unwanted isoform. It is necessary to investigate all of these processes in order to evaluate which variant may be causal for the deleterious phenotype. A great help in this regard are variant effect scores. Implemented as machine learning classifiers, they integrate annotations from different resources to rank genomic variants in terms of pathogenicity. Developing a variant effect score requires multiple steps: annotation of the training data, feature selection, model training, benchmarking, and finally deployment for the model's application. Here, I present a generalized workflow of this process. It makes it simple to configure how information is converted into model features, enabling the rapid exploration of different annotations. The workflow further implements hyperparameter optimization, model validation and ultimately deployment of a selected model via genome-wide scoring of genomic variants. The workflow is applied to train Combined Annotation Dependent Depletion (CADD), a variant effect model that is scoring SNVs and InDels genome-wide. I show that the workflow can be quickly adapted to novel annotations by porting CADD to the genome reference GRCh38. Further, I demonstrate the integration of deep-neural network scores as features into a new CADD model, improving the annotation of RNA splicing events. Finally, I apply the workflow to train multiple variant effect models from training data that is based on variants selected by allele frequency. In conclusion, the developed workflow presents a flexible and scalable method to train variant effect scores. All software and developed scores are freely available from cadd.gs.washington.edu and cadd.bihealth.org

    Ethnographies of Collaborative Economies across Europe: Understanding Sharing and Caring

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    "Sharing economy" and "collaborative economy" refer to a proliferation of initiatives, business models, digital platforms and forms of work that characterise contemporary life: from community-led initiatives and activist campaigns, to the impact of global sharing platforms in contexts such as network hospitality, transportation, etc. Sharing the common lens of ethnographic methods, this book presents in-depth examinations of collaborative economy phenomena. The book combines qualitative research and ethnographic methodology with a range of different collaborative economy case studies and topics across Europe. It uniquely offers a truly interdisciplinary approach. It emerges from a unique, long-term, multinational, cross-European collaboration between researchers from various disciplines (e.g., sociology, anthropology, geography, business studies, law, computing, information systems), career stages, and epistemological backgrounds, brought together by a shared research interest in the collaborative economy. This book is a further contribution to the in-depth qualitative understanding of the complexities of the collaborative economy phenomenon. These rich accounts contribute to the painting of a complex landscape that spans several countries and regions, and diverse political, cultural, and organisational backdrops. This book also offers important reflections on the role of ethnographic researchers, and on their stance and outlook, that are of paramount interest across the disciplines involved in collaborative economy research

    Blending the Material and Digital World for Hybrid Interfaces

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    The development of digital technologies in the 21st century is progressing continuously and new device classes such as tablets, smartphones or smartwatches are finding their way into our everyday lives. However, this development also poses problems, as these prevailing touch and gestural interfaces often lack tangibility, take little account of haptic qualities and therefore require full attention from their users. Compared to traditional tools and analog interfaces, the human skills to experience and manipulate material in its natural environment and context remain unexploited. To combine the best of both, a key question is how it is possible to blend the material world and digital world to design and realize novel hybrid interfaces in a meaningful way. Research on Tangible User Interfaces (TUIs) investigates the coupling between physical objects and virtual data. In contrast, hybrid interfaces, which specifically aim to digitally enrich analog artifacts of everyday work, have not yet been sufficiently researched and systematically discussed. Therefore, this doctoral thesis rethinks how user interfaces can provide useful digital functionality while maintaining their physical properties and familiar patterns of use in the real world. However, the development of such hybrid interfaces raises overarching research questions about the design: Which kind of physical interfaces are worth exploring? What type of digital enhancement will improve existing interfaces? How can hybrid interfaces retain their physical properties while enabling new digital functions? What are suitable methods to explore different design? And how to support technology-enthusiast users in prototyping? For a systematic investigation, the thesis builds on a design-oriented, exploratory and iterative development process using digital fabrication methods and novel materials. As a main contribution, four specific research projects are presented that apply and discuss different visual and interactive augmentation principles along real-world applications. The applications range from digitally-enhanced paper, interactive cords over visual watch strap extensions to novel prototyping tools for smart garments. While almost all of them integrate visual feedback and haptic input, none of them are built on rigid, rectangular pixel screens or use standard input modalities, as they all aim to reveal new design approaches. The dissertation shows how valuable it can be to rethink familiar, analog applications while thoughtfully extending them digitally. Finally, this thesis’ extensive work of engineering versatile research platforms is accompanied by overarching conceptual work, user evaluations and technical experiments, as well as literature reviews.Die Durchdringung digitaler Technologien im 21. Jahrhundert schreitet stetig voran und neue Geräteklassen wie Tablets, Smartphones oder Smartwatches erobern unseren Alltag. Diese Entwicklung birgt aber auch Probleme, denn die vorherrschenden berührungsempfindlichen Oberflächen berücksichtigen kaum haptische Qualitäten und erfordern daher die volle Aufmerksamkeit ihrer Nutzer:innen. Im Vergleich zu traditionellen Werkzeugen und analogen Schnittstellen bleiben die menschlichen Fähigkeiten ungenutzt, die Umwelt mit allen Sinnen zu begreifen und wahrzunehmen. Um das Beste aus beiden Welten zu vereinen, stellt sich daher die Frage, wie neuartige hybride Schnittstellen sinnvoll gestaltet und realisiert werden können, um die materielle und die digitale Welt zu verschmelzen. In der Forschung zu Tangible User Interfaces (TUIs) wird die Verbindung zwischen physischen Objekten und virtuellen Daten untersucht. Noch nicht ausreichend erforscht wurden hingegen hybride Schnittstellen, die speziell darauf abzielen, physische Gegenstände des Alltags digital zu erweitern und anhand geeigneter Designparameter und Entwurfsräume systematisch zu untersuchen. In dieser Dissertation wird daher untersucht, wie Materialität und Digitalität nahtlos ineinander übergehen können. Es soll erforscht werden, wie künftige Benutzungsschnittstellen nützliche digitale Funktionen bereitstellen können, ohne ihre physischen Eigenschaften und vertrauten Nutzungsmuster in der realen Welt zu verlieren. Die Entwicklung solcher hybriden Ansätze wirft jedoch übergreifende Forschungsfragen zum Design auf: Welche Arten von physischen Schnittstellen sind es wert, betrachtet zu werden? Welche Art von digitaler Erweiterung verbessert das Bestehende? Wie können hybride Konzepte ihre physischen Eigenschaften beibehalten und gleichzeitig neue digitale Funktionen ermöglichen? Was sind geeignete Methoden, um verschiedene Designs zu erforschen? Wie kann man Technologiebegeisterte bei der Erstellung von Prototypen unterstützen? Für eine systematische Untersuchung stützt sich die Arbeit auf einen designorientierten, explorativen und iterativen Entwicklungsprozess unter Verwendung digitaler Fabrikationsmethoden und neuartiger Materialien. Im Hauptteil werden vier Forschungsprojekte vorgestellt, die verschiedene visuelle und interaktive Prinzipien entlang realer Anwendungen diskutieren. Die Szenarien reichen von digital angereichertem Papier, interaktiven Kordeln über visuelle Erweiterungen von Uhrarmbändern bis hin zu neuartigen Prototyping-Tools für intelligente Kleidungsstücke. Um neue Designansätze aufzuzeigen, integrieren nahezu alle visuelles Feedback und haptische Eingaben, um Alternativen zu Standard-Eingabemodalitäten auf starren Pixelbildschirmen zu schaffen. Die Dissertation hat gezeigt, wie wertvoll es sein kann, bekannte, analoge Anwendungen zu überdenken und sie dabei gleichzeitig mit Bedacht digital zu erweitern. Dabei umfasst die vorliegende Arbeit sowohl realisierte technische Forschungsplattformen als auch übergreifende konzeptionelle Arbeiten, Nutzerstudien und technische Experimente sowie die Analyse existierender Forschungsarbeiten

    An overview of innovations in the external peer review of journal manuscripts.

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    Background: There are currently numerous innovations in peer review and quality assurance in scholarly publishing. The Research on Research Institute conducted a programme of co-produced projects investigating these innovations. This literature review was part of one such project ‘Experiments in peer review’ which created an inventory and framework of peer review innovations. The aim of this literature review was to aid the development of the inventory by identifying innovations in the external peer review of journal manuscripts reported in the scholarly literature and by providing a summary of the different approaches. This did not include interventions in editorial processes. Methods: This review of reviews is based on data identified from Web of Science and Scopus limited from 2010 to 2021. A total of 291 records were screened, with six review articles chosen for the focus of the literature review. Items were selected that described approaches to innovating peer review or illustrated examples. Results: The overview of innovations are drawn from six review articles. The innovations are divided into three high-level categories: approaches to peer review, reviewer focussed initiatives and technology to support peer review with sub-categories of results presented in tabular form and summarised. A summary of all innovations found is also presented. Conclusions: From a simple synthesis of the review authors’ conclusions, three key messages are presented: observations on current practice; authors’ views on the implications of innovations in peer review; and calls for action in peer review research and practice

    The regulation of digital platforms: the case of pagoPA

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    How can EU regulation affect innovation. Digital revolution: How big data have changed the world and the legal landscape. The regulation of digital platforms in Europe. Digital revolution: How distributed ledger technologies are changing the world and the legal landscape. Regulation of digital payments: the case of pagopa

    Synthetic Aperture Radar (SAR) Meets Deep Learning

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    This reprint focuses on the application of the combination of synthetic aperture radars and depth learning technology. It aims to further promote the development of SAR image intelligent interpretation technology. A synthetic aperture radar (SAR) is an important active microwave imaging sensor, whose all-day and all-weather working capacity give it an important place in the remote sensing community. Since the United States launched the first SAR satellite, SAR has received much attention in the remote sensing community, e.g., in geological exploration, topographic mapping, disaster forecast, and traffic monitoring. It is valuable and meaningful, therefore, to study SAR-based remote sensing applications. In recent years, deep learning represented by convolution neural networks has promoted significant progress in the computer vision community, e.g., in face recognition, the driverless field and Internet of things (IoT). Deep learning can enable computational models with multiple processing layers to learn data representations with multiple-level abstractions. This can greatly improve the performance of various applications. This reprint provides a platform for researchers to handle the above significant challenges and present their innovative and cutting-edge research results when applying deep learning to SAR in various manuscript types, e.g., articles, letters, reviews and technical reports

    Systems toxicology to advance human and environmental hazard assessment : A roadmap for advanced materials

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    Ideally, a Systems Toxicology (ST) approach is aimed at by (eco)toxicologists, i.e. a multidisciplinary area incorporating classical toxicological concepts with omics technologies, and the understanding of this through computational data sciences, chemistry, mathematics, and physics modelling. As outlined in sev-eral public reports (e.g. from ECHA-European Chemical Agency and EFSA-European Food Safety Authority), the way forward in the coming years in Europe is to integrate New Approach Methodologies (NAMs) (in-cluding omics technologies) into hazard and hence risk assessment (RA). Adverse Outcome Pathways (AOPs) describe a sequence of events in response to stress, from the molecular initiating event until an adverse outcome, which is relevant to RA or regulatory decision-making. AOPs are one of the facilitators to integrate mechanistic data into RA, but it is urgent to increase the inclusion of the vast mechanistic knowledge available, especially for the RA of novel smart and advanced materials (AdMa) with multi-functional characteristics. There are still many challenges to the routine usage of NAMs, e.g. omics-based information. Here, we summarise the current state of the art of ST, the benefits of human and environ-mental health cross knowledge and the available methods and output. The importance of this area has been highlighted for many years but is even more pressing in the context of AdMa. Furthermore, we outline the challenges and suggest recommendations for future implementation.(c) 2022 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).Peer reviewe

    Epidemiological methods to evaluate the early impact of the COVID-19 pandemic.

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    The early phase of the COVID-19 pandemic represented a major challenge for health systems and local Governments, with no drugs or vaccines available to provide a pharmaceutical response. In the absence of formal reporting, data gaps and repression by authorities, real-time open-source data can be mined for risk assessment and response early on. In this thesis, open-source and survey generated data was synthesized in novel ways to develop new epidemiological insights into the COVID-19 pandemic and advise public health policy. There were also controversies in areas where no data on risks associated with cruise ship travel, healthcare workers, aged-care, and mass gatherings was available. This thesis analyzed a range of these issues in the first year of the pandemic. In chapter 1, I summarized the literature on the COVID-19 pandemic and identified gaps in using open-source data for early responses to pandemics. In chapter 2, I assessed the impact of cruise ship travel on the transmission of COVID-19 both globally and in Australia. In chapter 3, in the absence of any reported data on healthcare workers, I estimated the burden of COVID-19 on Australian healthcare workers and the health system, by analyzing national healthcare worker infections and their occupational risk of COVID-19. Similarly, with no formal reporting on Australian COVID-19 aged-care infections and outbreaks, I estimated the burden of COVID-19 on Australian aged-care and aged-care workers in 2020, in chapter 4. With the controversy surrounding the May-June 2020, Black Lives Matter protests and COVID-19 associated risks, I estimated mask use and COVID-19 associated risks of these protests. In chapter 6, with the controversial mask mandates in Australia, I evaluated mask attitude and government and state sentiment during the COVID-19 pandemic in Sydney and Melbourne. This thesis highlights the value of open-source, and survey data, which provides good insights into population attitudes around public health issues and practice and can enhance routine surveillance, early warning, and response. With many countries now minimizing COVID-19, the use of this data is even more important as prevention and control of the COVID-19 pandemic requires both long-term public health and epidemiology measures
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