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A catalog of genetic loci associated with kidney function from analyses of a million individuals
(2019)
Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through transancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these,147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.
Increasing demand for analytical processing capabilities can be managed by replication approaches. However, to evenly balance the replicas' workload shares while at the same time minimizing the data replication factor is a highly challenging allocation problem. As optimal solutions are only applicable for small problem instances, effective heuristics are indispensable. In this paper, we test and compare state-of-the-art allocation algorithms for partial replication. By visualizing and exploring their (heuristic) solutions for different benchmark workloads, we are able to derive structural insights and to detect an algorithm's strengths as well as its potential for improvement. Further, our application enables end-to-end evaluations of different allocations to verify their theoretical performance.
With the emergence of the Internet of things (IoT), plenty of battery-powered and energy-harvesting devices are being deployed to fulfill sensing and actuation tasks in a variety of application areas, such as smart homes, precision agriculture, smart cities, and industrial automation. In this context, a critical issue is that of denial-of-sleep attacks. Such attacks temporarily or permanently deprive battery-powered, energy-harvesting, or otherwise energy-constrained devices of entering energy-saving sleep modes, thereby draining their charge. At the very least, a successful denial-of-sleep attack causes a long outage of the victim device. Moreover, to put battery-powered devices back into operation, their batteries have to be replaced. This is tedious and may even be infeasible, e.g., if a battery-powered device is deployed at an inaccessible location. While the research community came up with numerous defenses against denial-of-sleep attacks, most present-day IoT protocols include no denial-of-sleep defenses at all, presumably due to a lack of awareness and unsolved integration problems. After all, despite there are many denial-of-sleep defenses, effective defenses against certain kinds of denial-of-sleep attacks are yet to be found.
The overall contribution of this dissertation is to propose a denial-of-sleep-resilient medium access control (MAC) layer for IoT devices that communicate over IEEE 802.15.4 links. Internally, our MAC layer comprises two main components. The first main component is a denial-of-sleep-resilient protocol for establishing session keys among neighboring IEEE 802.15.4 nodes. The established session keys serve the dual purpose of implementing (i) basic wireless security and (ii) complementary denial-of-sleep defenses that belong to the second main component. The second main component is a denial-of-sleep-resilient MAC protocol. Notably, this MAC protocol not only incorporates novel denial-of-sleep defenses, but also state-of-the-art mechanisms for achieving low energy consumption, high throughput, and high delivery ratios. Altogether, our MAC layer resists, or at least greatly mitigates, all denial-of-sleep attacks against it we are aware of. Furthermore, our MAC layer is self-contained and thus can act as a drop-in replacement for IEEE 802.15.4-compliant MAC layers. In fact, we implemented our MAC layer in the Contiki-NG operating system, where it seamlessly integrates into an existing protocol stack.
A Landscape for Case Models
(2019)
Case Management is a paradigm to support knowledge-intensive processes. The different approaches developed for modeling these types of processes tend to result in scattered models due to the low abstraction level at which the inherently complex processes are therein represented. Thus, readability and understandability is more challenging than that of traditional process models. By reviewing existing proposals in the field of process overviews and case models, this paper extends a case modeling language - the fragment-based Case Management (fCM) language - with the goal of modeling knowledge-intensive processes from a higher abstraction level - to generate a so-called fCM landscape. This proposal is empirically evaluated via an online experiment. Results indicate that interpreting an fCM landscape might be more effective and efficient than interpreting an informationally equivalent case model.
Graph repair, restoring consistency of a graph, plays a prominent role in several areas of computer science and beyond: For example, in model-driven engineering, the abstract syntax of models is usually encoded using graphs. Flexible edit operations temporarily create inconsistent graphs not representing a valid model, thus requiring graph repair. Similarly, in graph databases—managing the storage and manipulation of graph data—updates may cause that a given database does not satisfy some integrity constraints, requiring also graph repair. We present a logic-based incremental approach to graph repair, generating a sound and complete (upon termination) overview of least-changing repairs. In our context, we formalize consistency by so-called graph conditions being equivalent to first-order logic on graphs. We present two kind of repair algorithms: State-based repair restores consistency independent of the graph update history, whereas deltabased (or incremental) repair takes this history explicitly into account. Technically, our algorithms rely on an existing model generation algorithm for graph conditions implemented in AutoGraph. Moreover, the delta-based approach uses the new concept of satisfaction (ST) trees for encoding if and how a graph satisfies a graph condition. We then demonstrate how to manipulate these STs incrementally with respect to a graph update.
Rapid advances in location-acquisition technologies have led to large amounts of trajectory data. This data is the foundation for a broad spectrum of services driven and improved by trajectory data mining. However, for hybrid transactional and analytical workloads, the storing and processing of rapidly accumulated trajectory data is a non-trivial task. In this paper, we present a detailed survey about state-of-the-art trajectory data management systems. To determine the relevant aspects and requirements for such systems, we developed a trajectory data mining framework, which summarizes the different steps in the trajectory data mining process. Based on the derived requirements, we analyze different concepts to store, compress, index, and process spatio-temporal data. There are various trajectory management systems, which are optimized for scalability, data footprint reduction, elasticity, or query performance. To get a comprehensive overview, we describe and compare different exciting systems. Additionally, the observed similarities in the general structure of different systems are consolidated in a general blueprint of trajectory management systems.
Business process improvement is an endless challenge for many organizations. As long as there is a process, it must he improved. Nowadays, improvement initiatives are driven by professionals. This is no longer practical because people cannot perceive the enormous data of current business environments. Here, we introduce ubiquitous decision-aware business processes. They pervade the physical space, analyze the ever-changing environments, and make decisions accordingly. We explain how they can be built and used for improvement. Our approach can be a valuable improvement option to alleviate the workload of participants by helping focus on the crucial rather than the menial tasks.
Working in iterations and repeatedly improving team workflows based on collected feedback is fundamental to agile software development processes. Scrum, the most popular agile method, provides dedicated retrospective meetings to reflect on the last development iteration and to decide on process improvement actions. However, agile methods do not prescribe how these improvement actions should be identified, managed or tracked in detail. The approaches to detect and remove problems in software development processes are therefore often based on intuition and prior experiences and perceptions of team members. Previous research in this area has focused on approaches to elicit a team's improvement opportunities as well as measurements regarding the work performed in an iteration, e.g. Scrum burn-down charts. Little research deals with the quality and nature of identified problems or how progress towards removing issues is measured. In this research, we investigate how agile development teams in the professional software industry organize their feedback and process improvement approaches. In particular, we focus on the structure and content of improvement and reflection meetings, i.e. retrospectives, and their outcomes. Researching how the vital mechanism of process improvement is implemented in practice in modern software development leads to a more complete picture of agile process improvement.
Machine learning (ML) pipelines for model training and validation typically include preprocessing, such as data cleaning and feature engineering, prior to training an ML model. Preprocessing combines relational algebra and user-defined functions (UDFs), while model training uses iterations and linear algebra. Current systems are tailored to either of the two. As a consequence, preprocessing and ML steps are optimized in isolation. To enable holistic optimization of ML training pipelines, we present Lara, a declarative domain-specific language for collections and matrices. Lara's inter-mediate representation (IR) reflects on the complete program, i.e., UDFs, control flow, and both data types. Two views on the IR enable diverse optimizations. Monads enable operator pushdown and fusion across type and loop boundaries. Combinators provide the semantics of domain-specific operators and optimize data access and cross-validation of ML algorithms. Our experiments on preprocessing pipelines and selected ML algorithms show the effects of our proposed optimizations on dense and sparse data, which achieve speedups of up to an order of magnitude.
Audit - and then what?
(2019)
Current trends such as digital transformation, Internet of Things, or Industry 4.0 are challenging the majority of learning factories. Regardless of whether a conventional learning factory, a model factory, or a digital learning factory, traditional approaches such as the monotonous execution of specific instructions don‘t suffice the learner’s needs, market requirements as well as especially current technological developments. Contemporary teaching environments need a clear strategy, a road to follow for being able to successfully cope with the changes and develop towards digitized learning factories. This demand driven necessity of transformation leads to another obstacle: Assessing the status quo and developing and implementing adequate action plans. Within this paper, details of a maturity-based audit of the hybrid learning factory in the Research and Application Centre Industry 4.0 and a thereof derived roadmap for the digitization of a learning factory are presented.