On Undetected Redundancy in the Burrows-Wheeler Transform

The Burrows-Wheeler-Transform (BWT) is an invertible permutation of a text known to be highly compressible but also useful for sequence analysis, what makes the BWT highly attractive for lossless data compression. In this paper, we present a new technique to reduce the size of a BWT using its combinatorial properties, while keeping it invertible. The technique can be applied to any BWT-based compressor, and, as experiments show, is able to reduce the encoding size by 8-16 % on average and up to 33-57 % in the best cases (depending on the BWT-compressor used), making BWT-based compressors competitive or even superior to today\u27s best lossless compressors

Edge minimization in de Bruijn graphs

This paper introduces the de Bruijn graph edge minimization problem, which is related to the compression of de Bruijn graphs: find the order-k de Bruijn graph with minimum edge count among all orders. We describe an efficient algorithm that solves this problem. Since the edge minimization problem is connected to the BWT compression technique called "tunneling", the paper also describes a way to minimize the length of a tunneled BWT in such a way that useful properties for sequence analysis are preserved. Although being a restriction, this is significant progress towards a solution to the open problem of finding optimal disjoint blocks that minimize space, as stated in Alanko et al. (DCC 2019).Comment: Accepted for Data Compression Conference 202

On the Observation of Vacuum Birefringence

We suggest an experiment to observe vacuum birefringence induced by intense laser fields. A high-intensity laser pulse is focused to ultra-relativistic intensity and polarizes the vacuum which then acts like a birefringent medium. The latter is probed by a linearly polarized x-ray pulse. We calculate the resulting ellipticity signal within strong-field QED assuming Gaussian beams. The laser technology required for detecting the signal will be available within the next three years.Comment: 4 pages, 4 figure

Communication breakdown : limits of spectro-temporal resolution for the perception of bat communication calls

Open Access funding enabled and organized by Projekt DEAL. This work was supported by the Human Frontier Science Program (Grant RGP0058 to UF).During vocal communication, the spectro-temporal structure of vocalizations conveys important contextual information. Bats excel in the use of sounds for echolocation by meticulous encoding of signals in the temporal domain. We therefore hypothesized that for social communication as well, bats would excel at detecting minute distortions in the spectro-temporal structure of calls. To test this hypothesis, we systematically introduced spectro-temporal distortion to communication calls of Phyllostomus discolor bats. We broke down each call into windows of the same length and randomized the phase spectrum inside each window. The overall degree of spectro-temporal distortion in communication calls increased with window length. Modelling the bat auditory periphery revealed that cochlear mechanisms allow discrimination of fast spectro-temporal envelopes. We evaluated model predictions with experimental psychophysical and neurophysiological data. We first assessed bats' performance in discriminating original versions of calls from increasingly distorted versions of the same calls. We further examined cortical responses to determine additional specializations for call discrimination at the cortical level. Psychophysical and cortical responses concurred with model predictions, revealing discrimination thresholds in the range of 8-15 ms randomization-window length. Our data suggest that specialized cortical areas are not necessary to impart psychophysical resilience to temporal distortion in communication calls.Publisher PDFPeer reviewe

Proceedings of the “Think Tank Hackathon’’, Big Data Training School for Life Sciences Follow-up, Ljubljana 6th – 7th February 2018

On 6th and 7th February 2018, a Think Tank took place in Ljubljana, Slovenia. It was a follow-up of the “Big Data Training School for Life Sciences” held in Uppsala, Sweden, in September 2017. The focus was on identifying topics of interest and optimising the programme for a forthcoming “Advanced” Big Data Training School for Life Science, that we hope is again supported by the COST Action CHARME (Harmonising standardisation strategies to increase efficiency and competitiveness of European life-science research - CA15110). The Think Tank aimed to go into details of several topics that were - to a degree - covered by the former training school. Likewise, discussions embraced the recent experience of the attendees in light of the new knowledge obtained by the first edition of the training school and how it comes from the perspective of their current and upcoming work. The 2018 training school should strive for and further facilitate optimised applications of Big Data technologies in life sciences. The attendees of this hackathon entirely organised this workshop.Peer ReviewedPostprint (published version

The radical induced cell death protein 1 (RCD1) supports transcriptional activation of genes for chloroplast antioxidant enzymes

The rimb1 (redox imbalanced 1) mutation was mapped to the RCD1 locus (radical- induced cell death 1; At1g32230) demonstrating that a major factor involved in redox-regulation genes for chloroplast antioxidant enzymes and protection against photooxidative stress, RIMB1, is identical to the regulator of disease response reactions and cell death, RCD1. Discovering this link let to our investigation of its regulatory mechanism. We show in yeast that RCD1 can physically interact with the transcription factor Rap2.4a which provides redox-sensitivity to nuclear expression of genes for chloroplast antioxidant enzymes. In the rimb1 (rcd1-6) mutant, a single nucleotide exchange results in a truncated RCD1 protein lacking the transcription factor binding site. Protein-protein interaction between full-length RCD1 and Rap2.4a is supported by H2O2, but not sensitive to the antioxidants dithiotreitol and ascorbate. In combination with transcript abundance analysis in Arabidopsis, it is concluded that RCD1 stabilizes the Rap2.4-dependent redox-regulation of the genes encoding chloroplast antioxidant enzymes in a widely redox-independent manner. Over the years, rcd1-mutant alleles have been described to develop symptoms like chlorosis, lesions along the leaf rims and in the mesophyll and (secondary) induction of extra- and intra-plastidic antioxidant defense mechanisms. All these rcd1 mutant characteristics were observed in rcd1-6 to succeed low activation of the chloroplast antioxidant system and glutathione biosynthesis. We conclude that RCD1 protects plant cells from running into reactive oxygen species (ROS)-triggered programs, such as cell death and activation of pathogen-responsive genes (PR genes) and extra-plastidic antioxidant enzymes, by supporting the induction of the chloroplast antioxidant system

Newly Developed CK1-Specific Inhibitors Show Specifically Stronger Effects on CK1 Mutants and Colon Cancer Cell Lines

Protein kinases of the CK1 family can be involved in numerous physiological and pathophysiological processes. Dysregulated expression and/or activity as well as mutation of CK1 isoforms have previously been linked to tumorigenesis. Among all neoplastic diseases, colon and rectal cancer (CRC) represent the fourth leading cause of cancer related deaths. Since mutations in CK1δ previously found in CRC patients exhibited increased oncogenic features, inhibition of CK1δ is supposed to have promising therapeutic potential for tumors, which present overexpression or mutations of this CK1 isoform. Therefore, it is important to develop new small molecule inhibitors exhibiting higher affinity toward CK1δ mutants. In the present study, we first characterized the kinetic properties of CK1δ mutants, which were detected in different tumor entities. Subsequently, we characterized the ability of several newly developed IWP-based inhibitors to inhibit wild type and CK1δ mutants and we furthermore analyzed their effects on growth inhibition of various cultured colon cancer cell lines. Our results indicate, that these compounds represent a promising base for the development of novel CRC therapy concepts

Zebrafish as model system for the biological characterization of CK1 inhibitors

Introduction: The CK1 family is involved in a variety of physiological processes by regulating different signaling pathways, including the Wnt/β-catenin, the Hedgehog and the p53 signaling pathways. Mutations or dysregulation of kinases in general and of CK1 in particular are known to promote the development of cancer, neurodegenerative diseases and inflammation. There is increasing evidence that CK1 isoform specific small molecule inhibitors, including CK1δ- and CK1ε-specific inhibitors of Wnt production (IWP)-based small molecules with structural similarity to benzimidazole compounds, have promising therapeutic potential.Methods: In this study, we investigated the suitability of the zebrafish model system for the evaluation of such CK1 inhibitors. To this end, the kinetic parameters of human CK1 isoforms were compared with those of zebrafish orthologues. Furthermore, the effects of selective CK1δ inhibition during zebrafish embryonic development were analyzed in vivo.Results: The results revealed that zebrafish CK1δA and CK1δB were inhibited as effectively as human CK1δ by compounds G2-2 with IC50 values of 345 and 270 nM for CK1δA and CK1δB versus 503 nM for human CK1δ and G2-3 exhibiting IC50 values of 514 and 561 nM for zebrafish CK1δA and B, and 562 nM for human CK1δ. Furthermore, the effects of selective CK1δ inhibition on zebrafish embryonic development in vivo revealed phenotypic abnormalities indicative of downregulation of CK1δ. Treatment of zebrafish embryos with selected inhibitors resulted in marked phenotypic changes including blood stasis, heart failure, and tail malformations.Conclusion: The results suggest that the zebrafish is a suitable in vivo assay model system for initial studies of the biological relevance of CK1δ inhibition

Investigating stratospheric changes between 2009 and 2018 with halogenated trace gas data from aircraft, AirCores, and a global model focusing on CFC-11

We present new observations of trace gases in the stratosphere based on a cost-effective sampling technique that can access much higher altitudes than aircraft. The further development of this method now provides detection of species with abundances in the parts per trillion (ppt) range and below. We obtain mixing ratios for six gases (CFC-11, CFC-12, HCFC-22, H-1211, H-1301, and SF6), all of which are important for understanding stratospheric ozone depletion and circulation. After demonstrating the quality of the data through comparisons with ground-based records and aircraft-based observations, we combine them with the latter to demonstrate its potential. We first compare the data with results from a global model driven by three widely used meteorological reanalyses. Secondly, we focus on CFC-11 as recent evidence has indicated renewed atmospheric emissions of that species relevant on a global scale. Because the stratosphere represents the main sink region for CFC-11, potential changes in stratospheric circulation and troposphere–stratosphere exchange fluxes have been identified as the largest source of uncertainty for the accurate quantification of such emissions. Our observations span over a decade (up until 2018) and therefore cover the period of the slowdown of CFC-11 global mixing ratio decreases measured at the Earth's surface. The spatial and temporal coverage of the observations is insufficient for a global quantitative analysis, but we do find some trends that are in contrast with expectations, indicating that the stratosphere may have contributed to the slower concentration decline in recent years. Further investigating the reanalysis-driven model data, we find that the dynamical changes in the stratosphere required to explain the apparent change in tropospheric CFC-11 emissions after 2013 are possible but with a very high uncertainty range. This is partly caused by the high variability of mass flux from the stratosphere to the troposphere, especially at timescales of a few years, and partly by large differences between runs driven by different reanalysis products, none of which agree with our observations well enough for such a quantitative analysis