We suggest a line of work for improving the current state-of-the art in computational methods for mass spectrometry. Our main focus is on increasing the chemical realism of the modeling of the fragmentation process. Two core ingredients of our proposal are i) describing the individual fragmentation reactions via graph transformation rules and ii) expressing the dynamics of the system via reaction rates and quasi-equilibrium theory. We use graph transformation rules both for specifying the possible core fragmentation reactions, and for characterizing the reaction sites when learning values for the rates. We employ a strategy framework in order to systematically expand the chemical space of fragments. We think that this approach in terms of chemical modeling is more mechanistically explicit than previous ones, and believe this can lead to both better spectrum prediction and more explanatory power. Our modeling of system dynamics also allows better separation of instrument dependent and instrument independent parameters of the model.

AbstractThe increasing availability of large digital corpora of cross-linguistic data is revolutionizing many branches of linguistics. Overall, it has triggered a shift of attention from detailed questions about individual features to more global patterns amenable to rigorous, but statistical, analyses. This engenders an approach based on successive approximations where models with simplified assumptions result in frameworks that can then be systematically refined, always keeping explicit the methodological commitments and the assumed prior knowledge. Therefore, they can resolve disputes between competing frameworks quantitatively by separating the support provided by the data from the underlying assumptions. These methods, though, often appear as a `black box' to traditional practitioners. In fact, the switch to a statistical view complicates comparison of the results from these newer methods with traditional understanding, sometimes leading to misinterpretation and overly broad claims. We describe here this evolving methodological shift, attributed to the advent of big, but often incomplete and poorly curated data, emphasizing the underlying similarity of the newer quantitative to the traditional comparative methods and discussing when and to what extent the former have advantages over the latter. In this review, we cover briefly both randomization tests for detecting patterns in a largely model-independent fashion and phylolinguistic methods for a more model-based analysis of these patterns. We foresee a fruitful division of labor between the ability to computationally process large volumes of data and the trained linguistic insight identifying worthy prior commitments and interesting hypotheses in need of comparison.

Managed multi-context systems (mMCSs) allow for the integration of heterogeneous knowledge sources in a modular and very general way. They were, however, mainly designed for static scenarios and are therefore not well-suited for dynamic environments in which continuous reasoning over such heterogeneous knowledge with constantly arriving streams of data is necessary. In this paper, we introduce reactive multi-context systems (rMCSs), a framework for reactive reasoning in the presence of heterogeneous knowledge sources and data streams. We show that rMCSs are indeed well-suited for this purpose by illustrating how several typical problems arising in the context of stream reasoning can be handled using them, by showing how inconsistencies possibly occurring in the integration of multiple knowledge sources can be handled, and by arguing that the potential non-determinism of rMCSs can be avoided if needed using an alternative, more skeptical well-founded semantics instead with beneficial computational properties. We also investigate the computational complexity of various reasoning problems related to rMCSs. Finally, we discuss related work, and show that rMCSs do not only generalize mMCSs to dynamic settings, but also capture/extend relevant approaches w.r.t. dynamics in knowledge representation and stream reasoning.

This column describes the efforts of a group of German knowledge representation and reasoning researchers to begin a research initiative focusing on hybrid reasoning.

Abstract Dialectical Frameworks (ADFs) generalize Dung's argumentation frameworks allowing various relationships among arguments to be expressed in a systematic way. We further generalize ADFs so as to accommodate arbitrary acceptance degrees for the arguments. This makes ADFs applicable in domains where both the initial status of arguments and their relationship are only insufficiently specified by Boolean functions. We define all standard ADF semantics for the weighted case, including grounded, preferred and stable semantics. We illustrate our approach using acceptance degrees from the unit interval and show how other valuation structures can be integrated. In each case it is sufficient to specify how the generalized acceptance conditions are represented by formulas, and to specify the information ordering underlying the characteristic ADF operator. We also present complexity results for problems related to weighted ADFs.

Abstract Dialectical Frameworks (ADFs) generalize Dung's argumentation frameworks allowing various relationships among arguments to be expressed in a systematic way. We further generalize ADFs so as to accommodate arbitrary acceptance degrees for the arguments. This makes ADFs applicable in domains where both the initial status of arguments and their relationship are only insufficiently specified by Boolean functions. We define all standard ADF semantics for the weighted case, including grounded, preferred and stable semantics. We illustrate our approach using acceptance degrees from the unit interval and show how other valuation structures can be integrated. In each case it is sufficient to specify how the generalized acceptance conditions are represented by formulas, and to specify the information ordering underlying the characteristic ADF operator. We also present complexity results for problems related to weighted ADFs.

Small nucleolar RNAs (snoRNAs) are essential players in the rRNA biogenesis due to their involvement in the nucleolytic processing of the precursor and the subsequent guidance of nucleoside modifications. Within the kingdom Fungi, merely a few species-specific surveys have explored their snoRNA repertoire. However, the wide range of the snoRNA landscape spanning all major fungal lineages has not been mapped so far, mainly because of missing tools for automatized snoRNA detection and functional analysis. For the first time, we report here a comprehensive inventory of fungal snoRNAs together with a functional analysis and an in-depth investigation of their evolutionary history including innovations, deletions, and target switches. This large-scale analysis, incorporating more than 120 snoRNA families with more than 7700 individual snoRNA sequences, catalogs and clarifies the landscape of fungal snoRNA families, assigns functions to previously orphan snoRNAs, and increases the number of sequences by 450%. We also show that the snoRNAome is subject to ongoing rearrangements and adaptations, e.g., through lineage-specific targets and redundant guiding functions.

Building systems that can communicate with humans is a core problem in Artificial Intelligence. This work proposes a novel neural network architecture for response selection in an end-to-end multi-turn conversational dialogue setting. The architecture applies context level attention and incorporates additional external knowledge provided by descriptions of domain-specific words. It uses a bi-directional Gated Recurrent Unit (GRU) for encoding context and responses and learns to attend over the context words given the latent response representation and vice versa. In addition, it incorporates external domain specific information using another GRU for encoding the domain keyword descriptions. This allows better representation of domain-specific keywords in responses and hence improves the overall performance. Experimental results show that our model outperforms all other state-of-the-art methods for response selection in multi-turn conversations.

Ontology learning (OL) is the process of automatically generating an ontological knowledge base from a plain text document. In this paper, we propose a new ontology learning approach and tool, called DLOL, which generates a knowledge base in the description logic (DL) SHOQ(D) from a collection of factual non-negative IS-A sentences in English. We provide extensive experimental results on the accuracy of DLOL, giving experimental comparisons to three state-of-the-art existing OL tools, namely Text2Onto, FRED, and LExO. Here, we use the standard OL accuracy measure, called lexical accuracy, and a novel OL accuracy measure, called instance-based inference model. In our experimental results, DLOL turns out to be about 21% and 46%, respectively, better than the best of the other three approaches.

AbstractGeneral cognitive function is a prominent and relatively stable human trait that is associated with many important life outcomes. We combine cognitive and genetic data from the CHARGE and COGENT consortia, and UK Biobank (total N = 300,486; age 16--102) and find 148 genome-wide significant independent loci (P −8) associated with general cognitive function. Within the novel genetic loci are variants associated with neurodegenerative and neurodevelopmental disorders, physical and psychiatric illnesses, and brain structure. Gene-based analyses find 709 genes associated with general cognitive function. Expression levels across the cortex are associated with general cognitive function. Using polygenic scores, up to 4.3% of variance in general cognitive function is predicted in independent samples. We detect significant genetic overlap between general cognitive function, reaction time, and many health variables including eyesight, hypertension, and longevity. In conclusion we identify novel genetic loci and pathways contributing to the heritability of general cognitive function.

BACKGROUND: The overall survival of patients with advanced and refractory oesophageal squamous cell carcinoma, mostly aged 65 years and older, is poor. Treatment with PD-1 antibodies showed improved progression-free survival and overall survival. We assessed the safety and efficacy of combined nivolumab and ipilimumab therapy in this population. METHODS: This multicentre, open-label, phase 2 trial done in 32 sites in Germany included patients aged 65 years and older with oesophageal squamous cell carcinoma and disease progression or recurrence following first-line therapy. Patients were treated with nivolumab (240 mg fixed dose once every 2 weeks, intravenously) in the safety run-in phase and continued with nivolumab and ipilimumab (nivolumab 240 mg fixed dose once every 2 weeks and ipilimumab 1 mg/kg once every 6 weeks, intravenously). The primary endpoint was overall survival, which was compared with a historical cohort receiving standard chemotherapy in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT03416244. FINDINGS: Between March 2, 2018, and Aug 20, 2020, we screened 75 patients with advanced oesophageal squamous cell carcinoma. We enrolled 66 patients (50 [76%] men and 16 [24%] women; median age 70·5 years [IQR 67·0-76·0]), 44 (67%) of whom received combined nivolumab and ipilimumab therapy and 22 (33%) received nivolumab alone. Median overall survival time at the prespecified data cutoff was 7·2 months (95% CI 5·7-12·4) and significantly higher than in a historical cohort receiving standard chemotherapy (p=0·0063). The most common treatment-related adverse events were fatigue (12 [29%] of 42), nausea (11 [26%]), and diarrhoea (ten [24%]). Grade 3-5 treatment-related adverse events occurred in 13 (20%) of 66 patients. Treatment-related death occurred in one patient with bronchiolitis obliterans while on nivolumab and ipilimumab treatment. INTERPRETATION: Patients aged at least 65 years, with advanced oesophageal squamous cell carcinoma might benefit from combined nivolumab and ipilimumab therapy in second-line treatment. FUNDING: Bristol Myers Squibb.

Large infrastructures of Internet companies, such as Facebook and Twitter, are composed of several layers of micro-services. While this modularity provides scalability to the system, the I/O associated with each service request strongly impacts its performance. In this context, writing concise programs which execute I/O efficiently is especially challenging. In this paper, we introduce "Yauhau, a novel compile-time solution. "Yauhau reduces the number of I/O calls through rewrites on a simple expression language. To execute I/O concurrently, it lowers the expression language to a dataflow representation. Our approach can be used alongside an existing programming language, permitting the use of legacy code. We describe an implementation in the JVM and use it to evaluate our approach. Experiments show that "Yauhau can significantly improve I/O, both in terms of the number of I/O calls and concurrent execution. "Yauhau outperforms state-of-the-art approaches with similar goals.

With the growth of the internet, the number of textitfake-news online has been proliferating every year. The consequences of such phenomena are manifold, ranging from lousy decision-making process to bullying and violence episodes. Therefore, fact-checking algorithms became a valuable asset. To this aim, an important step to detect fake-news is to have access to a credibility score for a given information source. However, most of the widely used Web indicators have either been shutdown to the public (e.g., Google PageRank) or are not free for use (Alexa Rank). Further existing databases are short-manually curated lists of online sources, which do not scale. Finally, most of the research on the topic is theoretical-based or explore confidential data in a restricted simulation environment. In this paper we explore current research, highlight the challenges and propose solutions to tackle the problem of classifying websites into a credibility scale. The proposed model automatically extracts source reputation cues and computes a credibility factor, providing valuable insights which can help in belittling dubious and confirming trustful unknown websites. Experimental results outperform state of the art in the 2-classes and 5-classes setting.

Among different characteristics of knowledge bases, data quality is one of the most relevant to maximize the benefits of the provided information. Knowledge base quality assessment poses a number of big data challenges such as high volume, variety, velocity, and veracity. In this article, we focus on answering questions related to the assessment of the veracity of facts through Deep Fact Validation (DeFacto), a triple validation framework designed to assess facts in RDF knowledge bases. Despite current developments in the research area, the underlying framework faces many challenges. This article pinpoints and discusses these issues and conducts a thorough analysis of its pipeline, aiming at reducing the error propagation through its components. Furthermore, we discuss recent developments related to this fact validation as well as describing advantages and drawbacks of state-of-the-art models. As a result of this exploratory analysis, we give insights and directions toward a better architecture to tackle the complex task of fact-checking in knowledge bases.

Carotid artery intima media thickness (cIMT) and carotid plaque are measures of subclinical atherosclerosis associated with ischemic stroke and coronary heart disease (CHD). Here, we undertake meta-analyses of genome-wide association studies (GWAS) in 71,128 individuals for cIMT, and 48,434 individuals for carotid plaque traits. We identify eight novel susceptibility loci for cIMT, one independent association at the previously-identified PINX1 locus, and one novel locus for carotid plaque. Colocalization analysis with nearby vascular expression quantitative loci (cis-eQTLs) derived from arterial wall and metabolic tissues obtained from patients with CHD identifies candidate genes at two potentially additional loci, ADAMTS9 and LOXL4. LD score regression reveals significant genetic correlations between cIMT and plaque traits, and both cIMT and plaque with CHD, any stroke subtype and ischemic stroke. Our study provides insights into genes and tissue-specific regulatory mechanisms linking atherosclerosis both to its functional genomic origins and its clinical consequences in humans.

The Webis MS MARCO Anchor Text 2022 dataset enriches Version 1 and 2 of the document collection of MS MARCO with anchor text extracted from six Common Crawl snapshots. The six Common Crawl snapshots cover the years 2016 to 2021 (between 1.7-3.4 billion documents each). We sampled 1,000 anchor texts for documents with more than 1,000 anchor texts at random and all anchor texts for documents with less than 1,000 anchor texts (this sampling yields that all anchor text is included for 94% of the documents in Version 1 and 97% of documents for Version 2). Overall, the MS MARCO Anchor Text 2022 dataset enriches 1,703,834 documents for Version 1 and 4,821,244 documents for Version 2 with anchor text. Cleaned versions of the MS MARCO Anchor Text 2022 dataset are available in ir_datasets, Zenodo and Hugging Face. The raw dataset with additional information and all metadata for the extracted anchor texts (roughly 100GB) is available on Hugging Face and files.webis.de. The details of the construction of the Webis MS MARCO Anchor Text 2022 dataset are described in the associated paper. If you use this dataset, please cite @InProceedingsfroebe:2022a, address = Berlin Heidelberg New York, author = Maik Fr``obe and Sebastian G''unther and Maximilian Probst and Martin Potthast and Matthias Hagen, booktitle = Advances in Information Retrieval. 44th European Conference on IR Research (ECIR 2022), editor = Matthias Hagen and Suzan Verberne and Craig Macdonald and Christin Seifert and Krisztian Balog and Kjetil Norvrag and Vinay Setty, month = apr, publisher = Springer, series = Lecture Notes in Computer Science, site = Stavanger, Norway, title = The Power of Anchor Text in the Neural Retrieval Era, year = 2022

BACKGROUND: Genome sequences and genome annotation data have become available at ever increasing rates in response to the rapid progress in sequencing technologies. As a consequence the demand for methods supporting comparative, evolutionary analysis is also growing. In particular, efficient tools to visualize-omics data simultaneously for multiple species are sorely lacking. A first and crucial step in this direction is the construction of a common coordinate system. Since genomes not only differ by rearrangements but also by large insertions, deletions, and duplications, the use of a single reference genome is insufficient, in particular when the number of species becomes large. RESULTS: The computational problem then becomes to determine an order and orientations of optimal local alignments that are as co-linear as possible with all the genome sequences. We first review the most prominent approaches to model the problem formally and then proceed to showing that it can be phrased as a particular variant of the Betweenness Problem. It is NP hard in general. As exact solutions are beyond reach for the problem sizes of practical interest, we introduce a collection of heuristic simplifiers to resolve ordering conflicts. CONCLUSION: Benchmarks on real-life data ranging from bacterial to fly genomes demonstrate the feasibility of computing good common coordinate systems.

System logs constitute valuable information for analysis and diagnosis of systems behavior. The analysis is highly time-consuming for large log volumes. For many parallel computing centers, outsourcing the analysis of system logs (syslogs) to third parties is the only option. Therefore, a general analysis and diagnosis solution is needed. Such a solution is possible only through the syslog analysis from multiple computing systems. The data within syslogs can be sensitive, thus obstructing the sharing of syslogs across institutions, third party entities, or in the public domain. This work proposes a new method for the anonymization of syslogs that employs de-identification and encoding to provide fully shareable system logs. In addition to eliminating the sensitive data within the test logs, the proposed anonymization method provides 25% performance improvement in post-processing of the anonymized syslogs, and more than 80% reduction in their required storage space.

System logs are valuable source of information for analyzing computing systems behavior. The message part of each system log entry includes detailed information about its respective event. RFC5424 provides general guidelines for generating system logs. However, the message part of system logs are unstructured and every software generates its system log messages independently. Automatic methods of analysis are required to analyze the large number of system logs generated on modern computing systems. Unstructured nature of system log messages, is a main challenge towards automatic analysis. Automatic text classification is a well-known approach to address this challenge. However, to use this approach, the target classes must be predefined. The common method is to apply machine learning on pre-classification text samples to generate a specific classifier for the respective text format. Our study indicates that in case of a high repetition frequency of system logs, the automatic classification of system log messages without pre-classified samples is possible. The preliminary results of analyzing one month of system logs on a production high performance cluster, indicate a very high accuracy. The classification accuracy has a direct relation with the available amount of system logs. The proposed classification method is automatic, unsupervised, and general.

System logs are a valuable source of information for the analysis and understanding of systems behavior for the purpose of improving their performance. Such logs contain various types of information, including sensitive information. Information deemed sensitive can either directly be extracted from system log entries by correlation of several log entries, or can be inferred from the combination of the (non-sensitive) information contained within system logs with other logs and/or additional datasets. The analysis of system logs containing sensitive information compromises data privacy. Therefore, various anonymization techniques, such as generalization and suppression have been employed, over the years, by data and computing centers to protect the privacy of their users, their data, and the system as a whole. Privacy-preserving data resulting from anonymization via generalization and suppression may lead to significantly decreased data usefulness, thus, hindering the intended analysis for understanding the system behavior. Maintaining a balance between data usefulness and privacy preservation, therefore, remains an open and important challenge. Irreversible encoding of system logs using collision-resistant hashing algorithms, such as SHAKE-128, is a novel approach previously introduced by the authors to mitigate data privacy concerns. The present work describes a study of the applicability of the encoding approach from earlier work on the system logs of a production high performance computing system. Moreover, a metric is introduced to assess the data usefulness of the anonymized system logs to detect and identify the failures encountered in the system.

Abstract Pan-cancer analyses that examine commonalities and differences among various cancer types have emerged as a powerful way to obtain novel insights into cancer biology. Here we present a comprehensive analysis of genetic alterations in a pan-cancer cohort including 961 tumours from children, adolescents, and young adults, comprising 24 distinct molecular types of cancer. Using a standardized workflow, we identified marked differences in terms of mutation frequency and significantly mutated genes in comparison to previously analysed adult cancers. Genetic alterations in 149 putative cancer driver genes separate the tumours into two classes: small mutation and structural/copy-number variant (correlating with germline variants). Structural variants, hyperdiploidy, and chromothripsis are linked to TP53 mutation status and mutational signatures. Our data suggest that 7--8% of the children in this cohort carry an unambiguous predisposing germline variant and that nearly 50% of paediatric neoplasms harbour a potentially druggable event, which is highly relevant for the design of future clinical trials.

Motivation: Many repetitive DNA elements are transcribed at appreciable expression levels. Mapping the corresponding RNA sequencing reads back to a reference genome is notoriously difficult and error-prone task, however. This is in particular true if chemical modifications introduce systematic mismatches, while at the same time the genomic loci are only approximately identical, as in the case of tRNAs. Results: We therefore developed a dedicated mapping strategy to handle RNA-seq reads that map to tRNAs relying on a modified target genome in which known tRNA loci are masked and instead intronless tRNA precursor sequences are appended as artificial 'chromosomes'. In a first pass, reads that overlap the boundaries of mature tRNAs are extracted. In the second pass, the remaining reads are mapped to a tRNA-masked target that is augmented by representative mature tRNA sequences. Using both simulated and real life data we show that our best-practice workflow removes most of the mapping artefacts introduced by simpler mapping schemes and makes it possible to reliably identify many of chemical tRNA modifications in generic small RNA-seq data. Using simulated data the FDR is only 2%. We find compelling evidence for tissue specific differences of tRNA modification patterns. Availability and implementation: The workflow is available both as a bash script and as a Galaxy workflow from https://github.com/AnneHoffmann/tRNA-read-mapping. Contact: fabian@tbi.univie.ac.at. Supplementary information: Supplementary data are available at Bioinformatics online.

The resection of brain tumors beneath eloquent areas of the human brain requires precise delineation of eloquent areas for maximum removal of tumor mass while minimizing the risk for postoperative functional deficits. Non-invasive mapping of eloquent areas can be carried out by intraoperative thermal imaging since neural activity alters the cortical temperature distribution. These characteristic changes in cortical temperature can be modeled by a response function. A prominent choice for this response function is the haemodynamic response function. However, the signal is typically superimposed by various effects such as motion artifacts, physiological effects, sensor drifts as well as autoregulation which have to be compensated.

The phylum Placozoa officially consists of only a single described species, Trichoplax adhaerens, although several lineages can be separated by molecular markers, geographical distributions and environmental demands. The placozoan 16S haplotype H2 (Trichoplax sp. H2) is the most robust and cosmopolitan lineage of placozoans found to date. In this study, its genome was found to be distinct but highly related to the Trichoplax adhaerens reference genome, for remarkably unique reasons. The pattern of variation and allele distribution between the two lineages suggests that both originate from a single interbreeding event in the wild, dating back at least several decades ago, and both seem not to have engaged in sexual reproduction since. We conclude that populations of certain placozoan haplotypes remain stable for long periods without bisexual reproduction. Furthermore, allelic variation within and between the two Trichoplax lineages indicates that successful bisexual reproduction between related placozoan lineages might serve to either counter accumulated negative somatic mutations or to cope with changing environmental conditions. On the other hand, enrichment of neutral or beneficial somatic mutations by vegetative reproduction, combined with rare sexual reproduction, could instantaneously boost genetic variation, generating novel ecotypes and eventually species.

The memory requirement of deep learning algorithms is considered incompatible with the memory restriction of energy-efficient hardware. A low memory footprint can be achieved by pruning obsolete connections or reducing the precision of connection strengths after the network has been trained. Yet, these techniques are not applicable to the case when neural networks have to be trained directly on hardware due to the hard memory constraints. Deep Rewiring (DEEP R) is a training algorithm which continuously rewires the network while preserving very sparse connectivity all along the training procedure. We apply DEEP R to a deep neural network implementation on a prototype chip of the 2nd generation SpiNNaker system. The local memory of a single core on this chip is limited to 64 KB and a deep network architecture is trained entirely within this constraint without the use of external memory. Throughout training, the proportion of active connections is limited to 1.3%. On the handwritten digits dataset MNIST, this extremely sparse network achieves 96.6% classification accuracy at convergence. Utilizing the multi-processor feature of the SpiNNaker system, we found very good scaling in terms of computation time, per-core memory consumption, and energy constraints. When compared to a X86 CPU implementation, neural network training on the SpiNNaker 2 prototype improves power and energy consumption by two orders of magnitude.

BACKGROUND: Heterotrimeric G proteins are fundamental signaling proteins composed of three subunits, G$alpha$ and a G$betagamma$ dimer. The role of G$alpha$ as a molecular switch is critical for transmitting and amplifying intracellular signaling cascades initiated by an activated G protein Coupled Receptor (GPCR). Despite their biochemical and therapeutic importance, the study of G protein evolution has been limited to the scope of a few model organisms. Furthermore, of the five primary G$alpha$ subfamilies, the underlying gene structure of only two families has been thoroughly investigated outside of Mammalia evolution. Therefore our understanding of G$alpha$ emergence and evolution across phylogeny remains incomplete. RESULTS: We have computationally identified the presence and absence of every G$alpha$ gene (GNA-) across all major branches of Deuterostomia and evaluated the conservation of the underlying exon-intron structures across these phylogenetic groups. We provide evidence of mutually exclusive exon inclusion through alternative splicing in specific lineages. Variations of splice site conservation and isoforms were found for several paralogs which coincide with conserved, putative motifs of DNA-/RNA-binding proteins. In addition to our curated gene annotations, within Primates, we identified 15 retrotranspositions, many of which have undergone pseudogenization. Most importantly, we find numerous deviations from previous findings regarding the presence and absence of individual GNA- genes, nuanced differences in phyla-specific gene copy numbers, novel paralog duplications and subsequent intron gain and loss events. CONCLUSIONS: Our curated annotations allow us to draw more accurate inferences regarding the emergence of all G$alpha$ family members across Metazoa and to present a new, updated theory of G$alpha$ evolution. Leveraging this, our results are critical for gaining new insights into the co-evolution of the G$alpha$ subunit and its many protein binding partners, especially therapeutically relevant G protein - GPCR signaling pathways which radiated in Vertebrata evolution.

Translating natural language to SQL queries for table-based question answering is a challenging problem and has received significant attention from the research community. In this work, we extend a pointer-generator and investigate the order-matters problem in semantic parsing for SQL. Even though our model is a straightforward extension of a general-purpose pointer-generator, it outperforms early works for WikiSQL and remains competitive to concurrently introduced, more complex models. Moreover, we provide a deeper investigation of the potential order-matters problem that could arise due to having multiple correct decoding paths, and investigate the use of REINFORCE as well as a dynamic oracle in this context.

The objective of this paper is twofold. The paper initially, based on the findings drawn from in-depth expert interviews with Innovation Laboratory (InnoLab) facilitators in field settings, explores the structural and functional diversity of existing InnoLabs. As a result, a service-based taxonomy of InnoLabs and a catalogue of their differentiating characteristics are constructed herein. Subsequently, the paper builds theory towards the inter-InnoLab collaboration. In this context, at first, the potential benefits of inter-InnoLab collaboration for the participating InnoLabs and their customers are determined. Successively, a roadmap of inter-InnoLab collaboration is constructed encompassing the various possible degrees of mutual integration of InnoLabs.

Recent breakthroughs in magnetic resonance imaging (MRI) enabled quantitative relaxometry and diffusion-weighted imaging with sub-millimeter resolution. Combined with biophysical models of MR contrast the emerging methods promise in vivo mapping of cyto- and myelo-architectonics, i.e., in vivo histology using MRI (hMRI) in humans. The hMRI methods require histological reference data for model building and validation. This is currently provided by MRI on post mortem human brain tissue in combination with classical histology on sections. However, this well established approach is limited to qualitative 2D information, while a systematic validation of hMRI requires quantitative 3D information on macroscopic voxels. We present a promising histological method based on optical 3D imaging combined with a tissue clearing method, Clear Lipid-exchanged Acrylamide-hybridized Rigid Imaging compatible Tissue hYdrogel (CLARITY), adapted for hMRI validation. Adapting CLARITY to the needs of hMRI is challenging due to poor antibody penetration into large sample volumes and high opacity of aged post mortem human brain tissue. In a pilot experiment we achieved transparency of up to 8 mm-thick and immunohistochemical staining of up to 5 mm-thick post mortem brain tissue by a combination of active and passive clearing, prolonged clearing and staining times. We combined 3D optical imaging of the cleared samples with tailored image processing methods. We demonstrated the feasibility for quantification of neuron density, fiber orientation distribution and cell type classification within a volume with size similar to a typical MRI voxel. The presented combination of MRI, 3D optical microscopy and image processing is a promising tool for validation of MRI-based microstructure estimates.

BACKGROUND: Inhibition of PCSK9 (proprotein convertase subtilisin/kexin type 9) is a novel strategy to treat hypercholesterolemia and reduce cardiovascular events. However, the potential role of circulating plasma PCSK9 concentrations as a diagnostic and predictive biomarker remains uncertain as of now. Here, we aimed to identify genetic variants associated with plasma PCSK9 and investigate possible causal effects on atherosclerotic vascular disease phenotypes. METHODS: We performed the first genome-wide association study of plasma PCSK9 levels in a cohort of suspected and confirmed coronary artery disease (LIFE-Heart; n=3290). RESULTS: Several independent variants at the PCSK9 gene locus were associated with circulating PCSK9 levels at genome-wide significance (lead SNP rs11591147, PCSK9-R46L; P=1.94$times$10-17). We discovered 4 independent PCSK9 SNPs explaining 4.4% of the variance of plasma PCSK9. In addition, we identified a genome-wide significant locus at chromosome 7p22.1 (rs6957201; P=7.01$times$10-9) and 7 suggestive hits (P<1$times$10-6). Using MR (Mendelian Randomization), we detected significant causal effects of circulating PCSK9 on coronary artery disease status and severity, carotid plaques, and intima-media thickness. CONCLUSIONS: Variants at the PCSK9 gene locus seem to be the major genetic determinants of plasma PCSK9 levels with 4 independent variants at the PCSK9 gene locus expressing allelic heterogeneity. The detected MR estimates support the hypothesis of a causal effect of PCSK9 on coronary artery disease and other vascular phenotypes. Other observed genetic associations for PCSK9 require validation in independent cohorts. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique Identifier: NCT00497887.

Clusters of paralogous genes such as the famous HOX cluster of developmental transcription factors tend to evolve by stepwise duplication of its members, often involving unequal crossing over. Gene conversion and possibly other mechanisms of concerted evolution further obfuscate the phylogenetic relationships. As a consequence, it is very difficult or even impossible to disentangle the detailed history of gene duplications in gene clusters. In this contribution we show that the expansion of gene clusters by unequal crossing over as proposed by Walter Gehring leads to distinctive patterns of genetic distances, namely a subclass of circular split systems. Furthermore, when the gene cluster was left undisturbed by genome rearrangements, the shortest Hamiltonian paths with respect to genetic distances coincide with the genomic order. This observation can be used to detect ancient genomic rearrangements of gene clusters and to distinguish gene clusters whose evolution was dominated by unequal crossing over within genes from those that expanded through other mechanisms.

Past research into decidable fragments of first-order logic (FO) has produced two very prominent fragments: the guarded fragment GF, and the two-variable fragment FO2. These fragments are of crucial importance because they provide significant insights into decidabil- ity and expressiveness of other (computational) logics like Modal Logics (MLs) and various Description Logics (DLs), which play a central role in Verification, Knowledge Represen- tation, and other areas. In this paper, we take a closer look at GF and FO2, and present a new fragment that subsumes them both. This fragment, called the triguarded fragment (denoted TGF), is obtained by relaxing the standard definition of GF: quantification is required to be guarded only for subformulae with three or more free variables. We show that, in the absence of equality, satisfiability in TGF is N2ExpTime-complete, but becomes NExpTime-complete if we bound the arity of predicates by a constant (a natural assumption in the context of MLs and DLs). Finally, we observe that many natural extensions of TGF, including the addition of equality, lead to undecidability.

Structured Knowledge on the Web had an intriguing history before it has become successful. We briefly revisit this history, before we go into the longer discussion about how structured knowledge on the Web should be devised such that it benefits even more applications. Core to this discussion will be issues like trust, information infrastructure usability and resilience, promising realms of structured knowledge and principles and practices of data sharing.

In the past decade Knowledge graphs have become very popular and frequently rely on the Resource Description Framework (RDF) or Property Graphs (PG) as their data models. However, the query languages for these two data models - SPARQL for RDF and the PG traversal language Gremlin - are lacking basic interoperability. In this demonstration paper, we present Gremlinator, the first translator from SPARQL - the W3C standardized language for RDF - to Gremlin - a popular property graph traversal language. Gremlinator translates SPARQL queries to Gremlin path traversals for executing graph pattern matching queries over graph databases. This allows a user, who is well versed in SPARQL, to access and query a wide variety of Graph databases avoiding the steep learning curve for adapting to a new Graph Query Language (GQL). Gremlin is a graph computing system-agnostic traversal language (covering both OLTP graph databases and OLAP graph processors), making it a desirable choice for supporting interoperability for querying Graph databases. Gremlinator is planned to be released as an Apache TinkerPop plugin in the upcoming releases.

Knowledge graphs have become popular over the past decade and frequently rely on the Resource Description Framework (RDF) or Property Graph (PG) databases as data models. However, the query languages for these two data models -- SPARQL for RDF and the PG traversal language Gremlin -- are lacking interoperability. We present Gremlinator, the first translator from SPARQL -- the W3C standardized language for RDF -- and Gremlin -- a popular property graph traversal language. Gremlinator translates SPARQL queries to Gremlin path traversals for executing graph pattern matching queries over graph databases. This allows a user, who is well versed in SPARQL, to access and query a wide variety of Graph Data Management Systems (DMSs) avoiding the steep learning curve for adapting to a new Graph Query Language (GQL). Gremlin is a graph computing system-agnostic traversal language (covering both OLTP graph database or OLAP graph processors), making it a desirable choice for supporting interoperability for querying Graph DMSs. Gremlinator currently supports the translation of a subset of SPARQL 1.0, specifically the SPARQL SELECT queries.

In a project called Ä Library of a Billion Words" we needed an implementation of the CTS protocol that is capable of handling a text collection containing at least 1 billion words. Because the existing solutions did not work for this scale or were still in development I started an implementation of the CTS protocol using methods that MySQL provides. Last year we published a paper that introduced a prototype with the core functionalities without being compliant with the specifications of CTS (Tiepmar et al., 2013). The purpose of this paper is to describe and evaluate the MySQL based implementation now that it is fulfilling the specifications version 5.0 rc.1 and mark it as finished and ready to use. Further information, online instances of CTS for all described datasets and binaries can be accessed via the projects website.

In academic discourse, the term Big Data is often used incorrectly or not considered in relevant use cases. This paper investigates the term Big Data in the context of text oriented digital humanities and in the process shows that it is not necessarily an issue of big data sets. The goal is to provide a starting point or a guideline for researchers in the humanities to relate their work to the concept of Big Data. It may even show the reader that they might be working on a task that can be considered as Big Data even though the data set itself is comparatively small. As such, this paper should not be seen as a concrete solution to specific problems but as a general overview that is based on several years of practical research experience. This paper also argues that interoperability is one of the most prominent Big Data issues in text oriented digital humanities.

Abstract argumentation frameworks are by now a major research area in knowledge representation and reasoning. Various aspects of AFs have been extensively studied over the last 25 years. Contributing to understanding the expressive power of AFs, researchers found lower and upper bounds for the maximal number of extensions, that is, acceptable points of view, in AFs. One of the classical and most important concepts in AFs are so-called complete extensions. Surprisingly, the exact bound for the maximal number of complete extensions in an AF has not yet been formally established, although there is a reasonable conjecture tracing back at least to 2015. Recently the notion of modularization was introduced and it was shown that this concept plays a key role for the understanding of relations between semantics as well as intrinsic properties. In this paper, we will use this property to give a formal proof of the conjecture regarding complete semantics.

We address the issue of quantitatively assessing the severity of inconsistencies in nonmonotonic frameworks. While measuring inconsistency in classical logics has been investigated for some time now, taking the nonmonotonicity into account poses new challenges. In order to tackle them, we focus on the structure of minimal strongly kb-inconsistent subsets of a knowledge base kb---a generalization of minimal inconsistency to arbitrary, possibly nonmonotonic, frameworks. We propose measures based on this notion and investigate their behavior in a nonmonotonic setting by revisiting existing rationality postulates, analyzing the compliance of the proposed measures with these postulates, and by investigating their computational complexity.

AbstractThe volume of the lateral ventricles (LV) increases with age and their abnormal enlargement is a key feature of several neurological and psychiatric diseases. Although lateral ventricular volume is heritable, a comprehensive investigation of its genetic determinants is lacking. In this meta-analysis of genome-wide association studies of 23,533 healthy middle-aged to elderly individuals from 26 population-based cohorts, we identify 7 genetic loci associated with LV volume. These loci map to chromosomes 3q28, 7p22.3, 10p12.31, 11q23.1, 12q23.3, 16q24.2, and 22q13.1 and implicate pathways related to tau pathology, S1P signaling, and cytoskeleton organization. We also report a significant genetic overlap between the thalamus and LV volumes ($rho$genetic = −0.59, p-value = 3.14 $times$ 10−6), suggesting that these brain structures may share a common biology. These genetic associations of LV volume provide insights into brain morphology.

Wikidata, now a decade old, is the largest public knowledge graph, with data on more than 100 million concepts contributed by over 560,000 editors. It is widely used in applications and research. At its launch in late 2012, however, it was little more than a hopeful new Wikimedia project, with no content, almost no community, and a severely restricted platform. Seven years earlier still, in 2005, it was merely a rough idea of a few PhD students, a conceptual nucleus that had yet to pick up many important influences from others to turn into what is now called Wikidata. In this paper, we try to recount this remarkable journey, and we review what has been accomplished, what has been given up on, and what is yet left to do for the future.

The telomerase RNA in yeasts is large, usually >1000 nt, and contains functional elements that have been extensively studied experimentally in several disparate species. Nevertheless, they are very difficult to detect by homology-based methods and so far have escaped annotation in the majority of the genomes of Saccharomycotina. This is a consequence of sequences that evolve rapidly at nucleotide level, are subject to large variations in size, and are highly plastic with respect to their secondary structures. Here, we report on a survey that was aimed at closing this gap in RNA annotation. Despite considerable efforts and the combination of a variety of different methods, it was only partially successful. While 27 new telomerase RNAs were identified, we had to restrict our efforts to the subgroup Saccharomycetacea because even this narrow subgroup was diverse enough to require different search models for different phylogenetic subgroups. More distant branches of the Saccharomycotina remain without annotated telomerase RNA.

BACKGROUND/OBJECTIVES: Acute pancreatitis (AP) is one of the most common gastrointestinal disorders often requiring hospitalization. Frequent aetiologies are gallstones and alcohol abuse. In contrast to chronic pancreatitis (CP) few robust genetic associations have been described. Here we analysed whether common variants in the CLDN2-MORC4 and the PRSS1-PRSS2 locus that increase recurrent AP and CP risk associate with AP. METHODS: We screened 1462 AP patients and 3999 controls with melting curve analysis for SNPs rs10273639 (PRSS1-PRSS2), rs7057398 (RIPPLY), and rs12688220 (MORC4). Calculations were performed for the overall group, aetiology, and gender sub-groups. To examine genotype-phenotype relationships we performed several meta-analyses. RESULTS: Meta-analyses of all AP patients depicted significant (p-value < 0.05) associations for rs10273639 (odds ratio (OR) 0.88, 95% confidence interval (CI) 0.81-0.97, p-value 0.01), rs7057398 (OR 1.27, 95% CI 1.07-1.5, p-value 0.005), and rs12688220 (OR 1.32, 95% CI 1.12-1.56, p-value 0.001). For the different aetiology groups a significant association was shown for rs10273639 (OR 0.76, 95% CI 0.63-0.92, p-value 0.005), rs7057398 (OR 1.43, 95% CI 1.07-1.92, p-value 0.02), and rs12688220 (OR 1.44, 95% CI 1.07-1.93, p-value 0.02) in the alcoholic sub-group only. CONCLUSIONS: The association of CP risk variants with different AP aetiologies, which is strongest in the alcoholic AP group, might implicate common pathomechanisms most likely between alcoholic AP and CP.

OBJECTIVE: Sierra Platinum is a fast and robust peak-caller for replicated ChIP-seq experiments with visual quality-control and -steering. The required computing resources are optimized but still may exceed the resources available to researchers at biological research institutes. RESULTS: Sierra Platinum Service provides the full functionality of Sierra Platinum: using a web interface, a new instance of the service can be generated. Then experimental data is uploaded and the computation of the peaks is started. Upon completion, the results can be inspected interactively and then downloaded for further analysis, at which point the service terminates.

This study aimed to understand the perception of drought among farmers, in order to support decision-making in the water allocation process. This study was carried out in the Tabuleiro de Russas irrigated perimeter, in northeast Brazil, over the drought period of 2012–2018. Two analyses were conducted: (i) drought characterization, using the Standardized Precipitation Index (SPI) based on drought duration and frequency criteria; and (ii) analysis of farmers’ perceptions of drought via selection of explanatory variables using the Random Forest (RF) and the Decision Tree (DT) methods. The 2012–2018 drought period was defined as a meteorological phenomenon by local farmers; however, an SPI evaluation indicated that the drought was of a hydrological nature. According to the RF analysis, four of the nine study variables were more statistically important than the others in influencing farmers’ perception of drought: number of cultivated land plots, farmer’s age, years of experience in the agriculture sector, and education level. These results were confirmed using DT analysis. Understanding the relationship between these variables and farmers’ perception of drought could aid in the development of an adaptation strategy to water deficit scenarios. Farmers’ perception can be beneficial in reducing conflicts, adopting proactive management practices, and developing a holistic and efficient early warning drought system.