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Large-scale databases that report the inhibitory capacities of many combinations of candidate drug compounds and cultivated cancer cell lines have driven the development of preclinical drug-sensitivity models based on machine learning. However, cultivated cell lines have devolved from human cancer cells over years or even decades under selective pressure in culture conditions. Moreover, models that have been trained on in vitro data cannot account for interactions with other types of cells. Drug-response data that are based on patient-derived cell cultures, xenografts, and organoids, on the other hand, are not available in the quantities that are needed to train high-capacity machine-learning models. We found that pre-training deep neural network models of drug sensitivity on in vitro drug-sensitivity databases before fine-tuning the model parameters on patient-derived data improves the models’ accuracy and improves the biological plausibility of the features, compared to training only on patient-derived data. From our experiments, we can conclude that pre-trained models outperform models that have been trained on the target domains in the vast majority of cases.
Answer Set Programming (ASP) is a paradigm for modeling and solving problems for knowledge representation and reasoning. There are plenty of results dedicated to studying the hardness of (fragments of) ASP. So far, these studies resulted in characterizations in terms of computational complexity as well as in fine-grained insights presented in form of dichotomy-style results, lower bounds when translating to other formalisms like propositional satisfiability (SAT), and even detailed parameterized complexity landscapes. A generic parameter in parameterized complexity originating from graph theory is the socalled treewidth, which in a sense captures structural density of a program. Recently, there was an increase in the number of treewidth-based solvers related to SAT. While there are translations from (normal) ASP to SAT, no reduction that preserves treewidth or at least keeps track of the treewidth increase is known. In this paper we propose a novel reduction from normal ASP to SAT that is aware of the treewidth, and guarantees that a slight increase of treewidth is indeed sufficient. Further, we show a new result establishing that, when considering treewidth, already the fragment of normal ASP is slightly harder than SAT (under reasonable assumptions in computational complexity). This also confirms that our reduction probably cannot be significantly improved and that the slight increase of treewidth is unavoidable. Finally, we present an empirical study of our novel reduction from normal ASP to SAT, where we compare treewidth upper bounds that are obtained via known decomposition heuristics. Overall, our reduction works better with these heuristics than existing translations. (c) 2021 Elsevier B.V. All rights reserved.
The highly structured nature of the educational sector demands effective policy mechanisms close to the needs of the field. That is why evidence-based policy making, endorsed by the European Commission under Erasmus+ Key Action 3, aims to make an alignment between the domains of policy and practice. Against this background, this article addresses two issues: First, that there is a vertical gap in the translation of higher-level policies to local strategies and regulations. Second, that there is a horizontal gap between educational domains regarding the policy awareness of individual players. This was analyzed in quantitative and qualitative studies with domain experts from the fields of virtual mobility and teacher training. From our findings, we argue that the combination of both gaps puts the academic bridge from secondary to tertiary education at risk, including the associated knowledge proficiency levels. We discuss the role of digitalization in the academic bridge by asking the question: which value does the involved stakeholders expect from educational policies? As a theoretical basis, we rely on the model of value co-creation for and by stakeholders. We describe the used instruments along with the obtained results and proposed benefits. Moreover, we reflect on the methodology applied, and we finally derive recommendations for future academic bridge policies.
Continuous verification of network security compliance is an accepted need. Especially, the analysis of stateful packet filters plays a central role for network security in practice. But the few existing tools which support the analysis of stateful packet filters are based on general applicable formal methods like Satifiability Modulo Theories (SMT) or theorem prover and show runtimes in the order of minutes to hours making them unsuitable for continuous compliance verification. In this work, we address these challenges and present the concept of state shell interweaving to transform a stateful firewall rule set into a stateless rule set. This allows us to reuse any fast domain specific engine from the field of data plane verification tools leveraging smart, very fast, and domain specialized data structures and algorithms including Header Space Analysis (HSA). First, we introduce the formal language FPL that enables a high-level human-understandable specification of the desired state of network security. Second, we demonstrate the instantiation of a compliance process using a verification framework that analyzes the configuration of complex networks and devices - including stateful firewalls - for compliance with FPL policies. Our evaluation results show the scalability of the presented approach for the well known Internet2 and Stanford benchmarks as well as for large firewall rule sets where it outscales state-of-the-art tools by a factor of over 41.
Computational drug sensitivity models have the potential to improve therapeutic outcomes by identifying targeted drug components that are likely to achieve the highest efficacy for a cancer cell line at hand at a therapeutic dose. State of the art drug sensitivity models use regression techniques to predict the inhibitory concentration of a drug for a tumor cell line. This regression objective is not directly aligned with either of these principal goals of drug sensitivity models: We argue that drug sensitivity modeling should be seen as a ranking problem with an optimization criterion that quantifies a drug's inhibitory capacity for the cancer cell line at hand relative to its toxicity for healthy cells. We derive an extension to the well-established drug sensitivity regression model PaccMann that employs a ranking loss and focuses on the ratio of inhibitory concentration and therapeutic dosage range. We find that the ranking extension significantly enhances the model's capability to identify the most effective anticancer drugs for unseen tumor cell profiles based in on in-vitro data.
The use of neural networks is considered as the state of the art in the field of image classification. A large number of different networks are available for this purpose, which, appropriately trained, permit a high level of classification accuracy. Typically, these networks are applied to uncompressed image data, since a corresponding training was also carried out using image data of similar high quality. However, if image data contains image errors, the classification accuracy deteriorates drastically. This applies in particular to coding artifacts which occur due to image and video compression. Typical application scenarios for video compression are narrowband transmission channels for which video coding is required but a subsequent classification is to be carried out on the receiver side. In this paper we present a special H.264/Advanced Video Codec (AVC) based video codec that allows certain regions of a picture to be coded with near constant picture quality in order to allow a reliable classification using neural networks, whereas the remaining image will be coded using constant bit rate. We have combined this feature with the ability to run with lowest latency properties, which is usually also required in remote control applications scenarios. The codec has been implemented as a fully hardwired High Definition video capable hardware architecture which is suitable for Field Programmable Gate Arrays.
Deep metric learning employs deep neural networks to embed instances into a metric space such that distances between instances of the same class are small and distances between instances from different classes are large. In most existing deep metric learning techniques, the embedding of an instance is given by a feature vector produced by a deep neural network and Euclidean distance or cosine similarity defines distances between these vectors. This paper studies deep distributional embeddings of sequences, where the embedding of a sequence is given by the distribution of learned deep features across the sequence. The motivation for this is to better capture statistical information about the distribution of patterns within the sequence in the embedding. When embeddings are distributions rather than vectors, measuring distances between embeddings involves comparing their respective distributions. The paper therefore proposes a distance metric based on Wasserstein distances between the distributions and a corresponding loss function for metric learning, which leads to a novel end-to-end trainable embedding model. We empirically observe that distributional embeddings outperform standard vector embeddings and that training with the proposed Wasserstein metric outperforms training with other distance functions.
Answer set planning
(2022)
Answer Set Planning refers to the use of Answer Set Programming (ASP) to compute plans, that is, solutions to planning problems, that transform a given state of the world to another state. The development of efficient and scalable answer set solvers has provided a significant boost to the development of ASP-based planning systems. This paper surveys the progress made during the last two and a half decades in the area of answer set planning, from its foundations to its use in challenging planning domains. The survey explores the advantages and disadvantages of answer set planning. It also discusses typical applications of answer set planning and presents a set of challenges for future research.
We present a method employing Answer Set Programming in combination with Approximate Model Counting for fast and accurate calculation of error propagation probabilities in digital circuits. By an efficient problem encoding, we achieve an input data format similar to a Verilog netlist so that extensive preprocessing is avoided. By a tight interconnection of our application with the underlying solver, we avoid iterating over fault sites and reduce calls to the solver. Several circuits were analyzed with varying numbers of considered cycles and different degrees of approximation. Our experiments show, that the runtime can be reduced by approximation by a factor of 91, whereas the error compared to the exact result is below 1%.
In this paper, we present a study comparing the depth to diameter (d/D) ratio of small simple craters (200-1000 m) of an area between -88.5 degrees to -90 degrees latitude at the lunar south pole containing Permanent Shadowed Regions (PSRs) versus craters without PSRs. As PSRs can reach temperatures of 110 K and are capable of harboring volatiles, especially water ice, we analyzed the relationship of depth versus diameter ratios and its possible implications for harboring water ice. Variations in the d/D ratios can also be caused by other processes such as degradation, isostatic adjustment, or differences in surface properties. The conducted d/D ratio analysis suggests that a differentiation between craters containing PSRs versus craters without PSRs occurs. Thus, a possible direct relation between d/D ratio, PSRs, and water ice harboring might exist. Our results suggest that differences in the target's surface properties may explain the obtained results. The resulting d/D ratios of craters with PSRs can help to select target areas for future In-Situ Resource Utilization (ISRU) missions.
The intensity of cosmic radiation may differ over five orders of magnitude within a few hours or days during the Solar Particle Events (SPEs), thus increasing for several orders of magnitude the probability of Single Event Upsets (SEUs) in space-borne electronic systems. Therefore, it is vital to enable the early detection of the SEU rate changes in order to ensure timely activation of dynamic radiation hardening measures. In this paper, an embedded approach for the prediction of SPEs and SRAM SEU rate is presented. The proposed solution combines the real-time SRAM-based SEU monitor, the offline-trained machine learning model and online learning algorithm for the prediction. With respect to the state-of-the-art, our solution brings the following benefits: (1) Use of existing on-chip data storage SRAM as a particle detector, thus minimizing the hardware and power overhead, (2) Prediction of SRAM SEU rate one hour in advance, with the fine-grained hourly tracking of SEU variations during SPEs as well as under normal conditions, (3) Online optimization of the prediction model for enhancing the prediction accuracy during run-time, (4) Negligible cost of hardware accelerator design for the implementation of selected machine learning model and online learning algorithm. The proposed design is intended for a highly dependable and self-adaptive multiprocessing system employed in space applications, allowing to trigger the radiation mitigation mechanisms before the onset of high radiation levels.
We study the concept of reversibility in connection with parallel communicating systems of finite automata (PCFA in short). We define the notion of reversibility in the case of PCFA (also covering the non-deterministic case) and discuss the relationship of the reversibility of the systems and the reversibility of its components. We show that a system can be reversible with non-reversible components, and the other way around, the reversibility of the components does not necessarily imply the reversibility of the system as a whole. We also investigate the computational power of deterministic centralized reversible PCFA. We show that these very simple types of PCFA (returning or non-returning) can recognize regular languages which cannot be accepted by reversible (deterministic) finite automata, and that they can even accept languages that are not context-free. We also separate the deterministic and non-deterministic variants in the case of systems with non-returning communication. We show that there are languages accepted by non-deterministic centralized PCFA, which cannot be recognized by any deterministic variant of the same type.
We introduce a new measure of descriptional complexity on finite automata, called the number of active states. Roughly speaking, the number of active states of an automaton A on input w counts the number of different states visited during the most economic computation of the automaton A for the word w. This concept generalizes to finite automata and regular languages in a straightforward way. We show that the number of active states of both finite automata and regular languages is computable, even with respect to nondeterministic finite automata. We further compare the number of active states to related measures for regular languages. In particular, we show incomparability to the radius of regular languages and that the difference between the number of active states and the total number of states needed in finite automata for a regular language can be of exponential order.
Image feature detection is a key task in computer vision. Scale Invariant Feature Transform (SIFT) is a prevalent and well known algorithm for robust feature detection. However, it is computationally demanding and software implementations are not applicable for real-time performance. In this paper, a versatile and pipelined hardware implementation is proposed, that is capable of computing keypoints and rotation invariant descriptors on-chip. All computations are performed in single precision floating-point format which makes it possible to implement the original algorithm with little alteration. Various rotation resolutions and filter kernel sizes are supported for images of any resolution up to ultra-high definition. For full high definition images, 84 fps can be processed. Ultra high definition images can be processed at 21 fps.
Large-scale literature mining to assess the relation between anti-cancer drugs and cancer types
(2021)
Background:
There is a huge body of scientific literature describing the relation between tumor types and anti-cancer drugs. The vast amount of scientific literature makes it impossible for researchers and physicians to extract all relevant information manually.
Methods:
In order to cope with the large amount of literature we applied an automated text mining approach to assess the relations between 30 most frequent cancer types and 270 anti-cancer drugs. We applied two different approaches, a classical text mining based on named entity recognition and an AI-based approach employing word embeddings. The consistency of literature mining results was validated with 3 independent methods: first, using data from FDA approvals, second, using experimentally measured IC-50 cell line data and third, using clinical patient survival data.
Results:
We demonstrated that the automated text mining was able to successfully assess the relation between cancer types and anti-cancer drugs. All validation methods showed a good correspondence between the results from literature mining and independent confirmatory approaches. The relation between most frequent cancer types and drugs employed for their treatment were visualized in a large heatmap. All results are accessible in an interactive web-based knowledge base using the following link: .
Conclusions:
Our approach is able to assess the relations between compounds and cancer types in an automated manner. Both, cancer types and compounds could be grouped into different clusters. Researchers can use the interactive knowledge base to inspect the presented results and follow their own research questions, for example the identification of novel indication areas for known drugs.
Student teachers often struggle to keep track of everything that is happening in the classroom, and particularly to notice and respond when students cause disruptions. The complexity of the classroom environment is a potential contributing factor that has not been empirically tested. In this experimental study, we utilized a virtual reality (VR) classroom to examine whether classroom complexity affects the likelihood of student teachers noticing disruptions and how they react after noticing. Classroom complexity was operationalized as the number of disruptions and the existence of overlapping disruptions (multidimensionality) as well as the existence of parallel teaching tasks (simultaneity). Results showed that student teachers (n = 50) were less likely to notice the scripted disruptions, and also less likely to respond to the disruptions in a comprehensive and effortful manner when facing greater complexity. These results may have implications for both teacher training and the design of VR for training or research purpose. This study contributes to the field from two aspects: 1) it revealed how features of the classroom environment can affect student teachers' noticing of and reaction to disruptions; and 2) it extends the functionality of the VR environment-from a teacher training tool to a testbed of fundamental classroom processes that are difficult to manipulate in real-life.
Background:
Pruritus often accompanies chronic skin diseases, exerting considerable burden on many areas of patient functioning; this burden and the features of pruritus remain insufficiently characterized.
Objective:
To investigate characteristics, including localization patterns, and burden of pruritus in patients with chronic dermatoses.
Methods:
We recruited 800 patients with active chronic skin diseases. We assessed pruritus intensity, localization, and further characteristics. We used validated questionnaires to assess quality of life, work productivity and activity impairment, anxiety, depression, and sleep quality.
Results:
Nine out of every 10 patients had experienced pruritus throughout their disease and 73% in the last 7 days. Pruritus often affected the entire body and was not restricted to skin lesions. Patients with moderate to severe pruritus reported significantly more impairment to their sleep quality and work productivity, and they were more depressed and anxious than control individuals and patients with mild or no pruritus. Suicidal ideations were highly prevalent in patients with chronic pruritus (18.5%) and atopic dermatitis (11.8%).
Conclusions:
Pruritus prevalence and intensity are very high across all dermatoses studied; intensity is linked to impairment in many areas of daily functioning. Effective treatment strategies are urgently required to treat pruritus and the underlying skin disease. ( J Am Acad Dermatol 2021;84:691-700.)
Tropical cyclones range among the costliest disasters on Earth. Their economic repercussions along the supply and trade network also affect remote economies that are not directly affected. We here simulate possible global repercussions on consumption for the example case of Hurricane Sandy in the US (2012) using the shock-propagation model Acclimate. The modeled shock yields a global three-phase ripple: an initial production demand reduction and associated consumption price decrease, followed by a supply shortage with increasing prices, and finally a recovery phase. Regions with strong trade relations to the US experience strong magnitudes of the ripple. A dominating demand reduction or supply shortage leads to overall consumption gains or losses of a region, respectively. While finding these repercussions in historic data is challenging due to strong volatility of economic interactions, numerical models like ours can help to identify them by approaching the problem from an exploratory angle, isolating the effect of interest. For this, our model simulates the economic interactions of over 7000 regional economic sectors, interlinked through about 1.8 million trade relations. Under global warming, the wave-like structures of the economic response to major hurricanes like the one simulated here are likely to intensify and potentially overlap with other weather extremes.
Due to climate change the frequency and character of precipitation are changing as the hydrological cycle intensifies. With regards to snowfall, global warming has two opposing influences; increasing humidity enables intense snowfall, whereas higher temperatures decrease the likelihood of snowfall. Here we show an intensification of extreme snowfall across large areas of the Northern Hemisphere under future warming. This is robust across an ensemble of global climate models when they are bias-corrected with observational data. While mean daily snowfall decreases, both the 99th and the 99.9th percentiles of daily snowfall increase in many regions in the next decades, especially for Northern America and Asia. Additionally, the average intensity of snowfall events exceeding these percentiles as experienced historically increases in many regions. This is likely to pose a challenge to municipalities in mid to high latitudes. Overall, extreme snowfall events are likely to become an increasingly important impact of climate change in the next decades, even if they will become rarer, but not necessarily less intense, in the second half of the century.
Stripe rust (Pst) is a major disease of wheat crops leading untreated to severe yield losses. The use of fungicides is often essential to control Pst when sudden outbreaks are imminent. Sensors capable of detecting Pst in wheat crops could optimize the use of fungicides and improve disease monitoring in high-throughput field phenotyping. Now, deep learning provides new tools for image recognition and may pave the way for new camera based sensors that can identify symptoms in early stages of a disease outbreak within the field. The aim of this study was to teach an image classifier to detect Pst symptoms in winter wheat canopies based on a deep residual neural network (ResNet). For this purpose, a large annotation database was created from images taken by a standard RGB camera that was mounted on a platform at a height of 2 m. Images were acquired while the platform was moved over a randomized field experiment with Pst-inoculated and Pst-free plots of winter wheat. The image classifier was trained with 224 x 224 px patches tiled from the original, unprocessed camera images. The image classifier was tested on different stages of the disease outbreak. At patch level the image classifier reached a total accuracy of 90%. To test the image classifier on image level, the image classifier was evaluated with a sliding window using a large striding length of 224 px allowing for fast test performance. At image level, the image classifier reached a total accuracy of 77%. Even in a stage with very low disease spreading (0.5%) at the very beginning of the Pst outbreak, a detection accuracy of 57% was obtained. Still in the initial phase of the Pst outbreak with 2 to 4% of Pst disease spreading, detection accuracy with 76% could be attained. With further optimizations, the image classifier could be implemented in embedded systems and deployed on drones, vehicles or scanning systems for fast mapping of Pst outbreaks.