@phdthesis{8983, abstract = {Metabolic adaptation is a critical feature of migrating cells. It tunes the metabolic programs of migrating cells to allow them to efficiently exert their crucial roles in development, inflammatory responses and tumor metastasis. Cell migration through physically challenging contexts requires energy. However, how the metabolic reprogramming that underlies in vivo cell invasion is controlled is still unanswered. In my PhD project, I identify a novel conserved metabolic shift in Drosophila melanogaster immune cells that by modulating their bioenergetic potential controls developmentally programmed tissue invasion. We show that this regulation requires a novel conserved nuclear protein, named Atossa. Atossa enhances the transcription of a set of proteins, including an RNA helicase Porthos and two metabolic enzymes, each of which increases the tissue invasion of leading Drosophila macrophages and can rescue the atossa mutant phenotype. Porthos selectively regulates the translational efficiency of a subset of mRNAs containing a 5’-UTR cis-regulatory TOP-like sequence. These 5’TOPL mRNA targets encode mitochondrial-related proteins, including subunits of mitochondrial oxidative phosphorylation (OXPHOS) components III and V and other metabolic-related proteins. Porthos powers up mitochondrial OXPHOS to engender a sufficient ATP supply, which is required for tissue invasion of leading macrophages. Atossa’s two vertebrate orthologs rescue the invasion defect. In my PhD project, I elucidate that Atossa displays a conserved developmental metabolic control to modulate metabolic capacities and the cellular energy state, through altered transcription and translation, to aid the tissue infiltration of leading cells into energy demanding barriers.}, author = {Emtenani, Shamsi}, issn = {2663-337X}, pages = {141}, publisher = {Institute of Science and Technology Austria}, title = {{Metabolic regulation of Drosophila macrophage tissue invasion}}, doi = {10.15479/AT:ISTA:8983}, year = {2020}, } @unpublished{8557, abstract = {The infiltration of immune cells into tissues underlies the establishment of tissue resident macrophages, and responses to infections and tumors. Yet the mechanisms immune cells utilize to negotiate tissue barriers in living organisms are not well understood, and a role for cortical actin has not been examined. Here we find that the tissue invasion of Drosophila macrophages, also known as plasmatocytes or hemocytes, utilizes enhanced cortical F-actin levels stimulated by the Drosophila member of the fos proto oncogene transcription factor family (Dfos, Kayak). RNA sequencing analysis and live imaging show that Dfos enhances F-actin levels around the entire macrophage surface by increasing mRNA levels of the membrane spanning molecular scaffold tetraspanin TM4SF, and the actin cross-linking filamin Cheerio which are themselves required for invasion. Cortical F-actin levels are critical as expressing a dominant active form of Diaphanous, a actin polymerizing Formin, can rescue the Dfos Dominant Negative macrophage invasion defect. In vivo imaging shows that Dfos is required to enhance the efficiency of the initial phases of macrophage tissue entry. Genetic evidence argues that this Dfos-induced program in macrophages counteracts the constraint produced by the tension of surrounding tissues and buffers the mechanical properties of the macrophage nucleus from affecting tissue entry. We thus identify tuning the cortical actin cytoskeleton through Dfos as a key process allowing efficient forward movement of an immune cell into surrounding tissues.}, author = {Belyaeva, Vera and Wachner, Stephanie and Gridchyn, Igor and Linder, Markus and Emtenani, Shamsi and György, Attila and Sibilia, Maria and Siekhaus, Daria E}, booktitle = {bioRxiv}, title = {{Cortical actin properties controlled by Drosophila Fos aid macrophage infiltration against surrounding tissue resistance}}, doi = {10.1101/2020.09.18.301481}, year = {2020}, } @unpublished{8831, abstract = {Holes in planar Ge have high mobilities, strong spin-orbit interaction and electrically tunable g-factors, and are therefore emerging as a promising candidate for hybrid superconductorsemiconductor devices. This is further motivated by the observation of supercurrent transport in planar Ge Josephson Field effect transistors (JoFETs). A key challenge towards hybrid germanium quantum technology is the design of high quality interfaces and superconducting contacts that are robust against magnetic fields. By combining the assets of Al, which has a long superconducting coherence, and Nb, which has a significant superconducting gap, we form low-disordered JoFETs with large ICRN products that are capable of withstanding high magnetic fields. We furthermore demonstrate the ability of phase-biasing individual JoFETs opening up an avenue to explore topological superconductivity in planar Ge. The persistence of superconductivity in the reported hybrid devices beyond 1.8 T paves the way towards integrating spin qubits and proximity-induced superconductivity on the same chip.}, author = {Aggarwal, Kushagra and Hofmann, Andrea C and Jirovec, Daniel and Prieto Gonzalez, Ivan and Sammak, Amir and Botifoll, Marc and Marti-Sanchez, Sara and Veldhorst, Menno and Arbiol, Jordi and Scappucci, Giordano and Katsaros, Georgios}, booktitle = {arXiv}, title = {{Enhancement of proximity induced superconductivity in planar Germanium}}, year = {2020}, } @article{8532, abstract = {The molecular anatomy of synapses defines their characteristics in transmission and plasticity. Precise measurements of the number and distribution of synaptic proteins are important for our understanding of synapse heterogeneity within and between brain regions. Freeze–fracture replica immunogold electron microscopy enables us to analyze them quantitatively on a two-dimensional membrane surface. Here, we introduce Darea software, which utilizes deep learning for analysis of replica images and demonstrate its usefulness for quick measurements of the pre- and postsynaptic areas, density and distribution of gold particles at synapses in a reproducible manner. We used Darea for comparing glutamate receptor and calcium channel distributions between hippocampal CA3-CA1 spine synapses on apical and basal dendrites, which differ in signaling pathways involved in synaptic plasticity. We found that apical synapses express a higher density of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors and a stronger increase of AMPA receptors with synaptic size, while basal synapses show a larger increase in N-methyl-D-aspartate (NMDA) receptors with size. Interestingly, AMPA and NMDA receptors are segregated within postsynaptic sites and negatively correlated in density among both apical and basal synapses. In the presynaptic sites, Cav2.1 voltage-gated calcium channels show similar densities in apical and basal synapses with distributions consistent with an exclusion zone model of calcium channel-release site topography.}, author = {Kleindienst, David and Montanaro-Punzengruber, Jacqueline-Claire and Bhandari, Pradeep and Case, Matthew J and Fukazawa, Yugo and Shigemoto, Ryuichi}, issn = {14220067}, journal = {International Journal of Molecular Sciences}, number = {18}, publisher = {MDPI}, title = {{Deep learning-assisted high-throughput analysis of freeze-fracture replica images applied to glutamate receptors and calcium channels at hippocampal synapses}}, doi = {10.3390/ijms21186737}, volume = {21}, year = {2020}, } @inproceedings{7810, abstract = {Interprocedural data-flow analyses form an expressive and useful paradigm of numerous static analysis applications, such as live variables analysis, alias analysis and null pointers analysis. The most widely-used framework for interprocedural data-flow analysis is IFDS, which encompasses distributive data-flow functions over a finite domain. On-demand data-flow analyses restrict the focus of the analysis on specific program locations and data facts. This setting provides a natural split between (i) an offline (or preprocessing) phase, where the program is partially analyzed and analysis summaries are created, and (ii) an online (or query) phase, where analysis queries arrive on demand and the summaries are used to speed up answering queries. In this work, we consider on-demand IFDS analyses where the queries concern program locations of the same procedure (aka same-context queries). We exploit the fact that flow graphs of programs have low treewidth to develop faster algorithms that are space and time optimal for many common data-flow analyses, in both the preprocessing and the query phase. We also use treewidth to develop query solutions that are embarrassingly parallelizable, i.e. the total work for answering each query is split to a number of threads such that each thread performs only a constant amount of work. Finally, we implement a static analyzer based on our algorithms, and perform a series of on-demand analysis experiments on standard benchmarks. Our experimental results show a drastic speed-up of the queries after only a lightweight preprocessing phase, which significantly outperforms existing techniques.}, author = {Chatterjee, Krishnendu and Goharshady, Amir Kafshdar and Ibsen-Jensen, Rasmus and Pavlogiannis, Andreas}, booktitle = {European Symposium on Programming}, isbn = {9783030449131}, issn = {16113349}, location = {Dublin, Ireland}, pages = {112--140}, publisher = {Springer Nature}, title = {{Optimal and perfectly parallel algorithms for on-demand data-flow analysis}}, doi = {10.1007/978-3-030-44914-8_5}, volume = {12075}, year = {2020}, } @inproceedings{8728, abstract = {Discrete-time Markov Chains (MCs) and Markov Decision Processes (MDPs) are two standard formalisms in system analysis. Their main associated quantitative objectives are hitting probabilities, discounted sum, and mean payoff. Although there are many techniques for computing these objectives in general MCs/MDPs, they have not been thoroughly studied in terms of parameterized algorithms, particularly when treewidth is used as the parameter. This is in sharp contrast to qualitative objectives for MCs, MDPs and graph games, for which treewidth-based algorithms yield significant complexity improvements. In this work, we show that treewidth can also be used to obtain faster algorithms for the quantitative problems. For an MC with n states and m transitions, we show that each of the classical quantitative objectives can be computed in O((n+m)⋅t2) time, given a tree decomposition of the MC with width t. Our results also imply a bound of O(κ⋅(n+m)⋅t2) for each objective on MDPs, where κ is the number of strategy-iteration refinements required for the given input and objective. Finally, we make an experimental evaluation of our new algorithms on low-treewidth MCs and MDPs obtained from the DaCapo benchmark suite. Our experiments show that on low-treewidth MCs and MDPs, our algorithms outperform existing well-established methods by one or more orders of magnitude.}, author = {Asadi, Ali and Chatterjee, Krishnendu and Goharshady, Amir Kafshdar and Mohammadi, Kiarash and Pavlogiannis, Andreas}, booktitle = {Automated Technology for Verification and Analysis}, isbn = {9783030591519}, issn = {1611-3349}, location = {Hanoi, Vietnam}, pages = {253--270}, publisher = {Springer Nature}, title = {{Faster algorithms for quantitative analysis of MCs and MDPs with small treewidth}}, doi = {10.1007/978-3-030-59152-6_14}, volume = {12302}, year = {2020}, } @inproceedings{8089, abstract = {We consider the classical problem of invariant generation for programs with polynomial assignments and focus on synthesizing invariants that are a conjunction of strict polynomial inequalities. We present a sound and semi-complete method based on positivstellensaetze, i.e. theorems in semi-algebraic geometry that characterize positive polynomials over a semi-algebraic set. On the theoretical side, the worst-case complexity of our approach is subexponential, whereas the worst-case complexity of the previous complete method (Kapur, ACA 2004) is doubly-exponential. Even when restricted to linear invariants, the best previous complexity for complete invariant generation is exponential (Colon et al, CAV 2003). On the practical side, we reduce the invariant generation problem to quadratic programming (QCLP), which is a classical optimization problem with many industrial solvers. We demonstrate the applicability of our approach by providing experimental results on several academic benchmarks. To the best of our knowledge, the only previous invariant generation method that provides completeness guarantees for invariants consisting of polynomial inequalities is (Kapur, ACA 2004), which relies on quantifier elimination and cannot even handle toy programs such as our running example.}, author = {Chatterjee, Krishnendu and Fu, Hongfei and Goharshady, Amir Kafshdar and Goharshady, Ehsan Kafshdar}, booktitle = {Proceedings of the 41st ACM SIGPLAN Conference on Programming Language Design and Implementation}, isbn = {9781450376136}, location = {London, United Kingdom}, pages = {672--687}, publisher = {Association for Computing Machinery}, title = {{Polynomial invariant generation for non-deterministic recursive programs}}, doi = {10.1145/3385412.3385969}, year = {2020}, } @article{6918, abstract = {We consider the classic problem of Network Reliability. A network is given together with a source vertex, one or more target vertices, and probabilities assigned to each of the edges. Each edge of the network is operable with its associated probability and the problem is to determine the probability of having at least one source-to-target path that is entirely composed of operable edges. This problem is known to be NP-hard. We provide a novel scalable algorithm to solve the Network Reliability problem when the treewidth of the underlying network is small. We also show our algorithm’s applicability for real-world transit networks that have small treewidth, including the metro networks of major cities, such as London and Tokyo. Our algorithm leverages tree decompositions to shrink the original graph into much smaller graphs, for which reliability can be efficiently and exactly computed using a brute force method. To the best of our knowledge, this is the first exact algorithm for Network Reliability that can scale to handle real-world instances of the problem.}, author = {Goharshady, Amir Kafshdar and Mohammadi, Fatemeh}, issn = {09518320}, journal = {Reliability Engineering and System Safety}, publisher = {Elsevier}, title = {{An efficient algorithm for computing network reliability in small treewidth}}, doi = {10.1016/j.ress.2019.106665}, volume = {193}, year = {2020}, } @article{7161, abstract = {In this paper, we introduce an inertial projection-type method with different updating strategies for solving quasi-variational inequalities with strongly monotone and Lipschitz continuous operators in real Hilbert spaces. Under standard assumptions, we establish different strong convergence results for the proposed algorithm. Primary numerical experiments demonstrate the potential applicability of our scheme compared with some related methods in the literature.}, author = {Shehu, Yekini and Gibali, Aviv and Sagratella, Simone}, issn = {1573-2878}, journal = {Journal of Optimization Theory and Applications}, pages = {877–894}, publisher = {Springer Nature}, title = {{Inertial projection-type methods for solving quasi-variational inequalities in real Hilbert spaces}}, doi = {10.1007/s10957-019-01616-6}, volume = {184}, year = {2020}, } @article{7652, abstract = {Organisms cope with change by taking advantage of transcriptional regulators. However, when faced with rare environments, the evolution of transcriptional regulators and their promoters may be too slow. Here, we investigate whether the intrinsic instability of gene duplication and amplification provides a generic alternative to canonical gene regulation. Using real-time monitoring of gene-copy-number mutations in Escherichia coli, we show that gene duplications and amplifications enable adaptation to fluctuating environments by rapidly generating copy-number and, therefore, expression-level polymorphisms. This amplification-mediated gene expression tuning (AMGET) occurs on timescales that are similar to canonical gene regulation and can respond to rapid environmental changes. Mathematical modelling shows that amplifications also tune gene expression in stochastic environments in which transcription-factor-based schemes are hard to evolve or maintain. The fleeting nature of gene amplifications gives rise to a generic population-level mechanism that relies on genetic heterogeneity to rapidly tune the expression of any gene, without leaving any genomic signature.}, author = {Tomanek, Isabella and Grah, Rok and Lagator, M. and Andersson, A. M. C. and Bollback, Jonathan P and Tkačik, Gašper and Guet, Calin C}, issn = {2397-334X}, journal = {Nature Ecology & Evolution}, number = {4}, pages = {612--625}, publisher = {Springer Nature}, title = {{Gene amplification as a form of population-level gene expression regulation}}, doi = {10.1038/s41559-020-1132-7}, volume = {4}, year = {2020}, } @phdthesis{7258, abstract = {Many flows encountered in nature and applications are characterized by a chaotic motion known as turbulence. Turbulent flows generate intense friction with pipe walls and are responsible for considerable amounts of energy losses at world scale. The nature of turbulent friction and techniques aimed at reducing it have been subject of extensive research over the last century, but no definite answer has been found yet. In this thesis we show that in pipes at moderate turbulent Reynolds numbers friction is better described by the power law first introduced by Blasius and not by the Prandtl–von Kármán formula. At higher Reynolds numbers, large scale motions gradually become more important in the flow and can be related to the change in scaling of friction. Next, we present a series of new techniques that can relaminarize turbulence by suppressing a key mechanism that regenerates it at walls, the lift–up effect. In addition, we investigate the process of turbulence decay in several experiments and discuss the drag reduction potential. Finally, we examine the behavior of friction under pulsating conditions inspired by the human heart cycle and we show that under such circumstances turbulent friction can be reduced to produce energy savings.}, author = {Scarselli, Davide}, issn = {2663-337X}, pages = {174}, publisher = {Institute of Science and Technology Austria}, title = {{New approaches to reduce friction in turbulent pipe flow}}, doi = {10.15479/AT:ISTA:7258}, year = {2020}, } @phdthesis{8653, abstract = {Mutations are the raw material of evolution and come in many different flavors. Point mutations change a single letter in the DNA sequence, while copy number mutations like duplications or deletions add or remove many letters of the DNA sequence simultaneously. Each type of mutation exhibits specific properties like its rate of formation and reversal. Gene expression is a fundamental phenotype that can be altered by both, point and copy number mutations. The following thesis is concerned with the dynamics of gene expression evolution and how it is affected by the properties exhibited by point and copy number mutations. Specifically, we are considering i) copy number mutations during adaptation to fluctuating environments and ii) the interaction of copy number and point mutations during adaptation to constant environments.  }, author = {Tomanek, Isabella}, issn = {2663-337X}, keywords = {duplication, amplification, promoter, CNV, AMGET, experimental evolution, Escherichia coli}, pages = {117}, publisher = {Institute of Science and Technology Austria}, title = {{The evolution of gene expression by copy number and point mutations}}, doi = {10.15479/AT:ISTA:8653}, year = {2020}, } @article{7427, abstract = {Plants, like other multicellular organisms, survive through a delicate balance between growth and defense against pathogens. Salicylic acid (SA) is a major defense signal in plants, and the perception mechanism as well as downstream signaling activating the immune response are known. Here, we identify a parallel SA signaling that mediates growth attenuation. SA directly binds to A subunits of protein phosphatase 2A (PP2A), inhibiting activity of this complex. Among PP2A targets, the PIN2 auxin transporter is hyperphosphorylated in response to SA, leading to changed activity of this important growth regulator. Accordingly, auxin transport and auxin-mediated root development, including growth, gravitropic response, and lateral root organogenesis, are inhibited. This study reveals how SA, besides activating immunity, concomitantly attenuates growth through crosstalk with the auxin distribution network. Further analysis of this dual role of SA and characterization of additional SA-regulated PP2A targets will provide further insights into mechanisms maintaining a balance between growth and defense.}, author = {Tan, Shutang and Abas, Melinda F and Verstraeten, Inge and Glanc, Matous and Molnar, Gergely and Hajny, Jakub and Lasák, Pavel and Petřík, Ivan and Russinova, Eugenia and Petrášek, Jan and Novák, Ondřej and Pospíšil, Jiří and Friml, Jiří}, issn = {09609822}, journal = {Current Biology}, number = {3}, pages = {381--395.e8}, publisher = {Cell Press}, title = {{Salicylic acid targets protein phosphatase 2A to attenuate growth in plants}}, doi = {10.1016/j.cub.2019.11.058}, volume = {30}, year = {2020}, } @article{7500, abstract = {Plant survival depends on vascular tissues, which originate in a self‐organizing manner as strands of cells co‐directionally transporting the plant hormone auxin. The latter phenomenon (also known as auxin canalization) is classically hypothesized to be regulated by auxin itself via the effect of this hormone on the polarity of its own intercellular transport. Correlative observations supported this concept, but molecular insights remain limited. In the current study, we established an experimental system based on the model Arabidopsis thaliana, which exhibits auxin transport channels and formation of vasculature strands in response to local auxin application. Our methodology permits the genetic analysis of auxin canalization under controllable experimental conditions. By utilizing this opportunity, we confirmed the dependence of auxin canalization on a PIN‐dependent auxin transport and nuclear, TIR1/AFB‐mediated auxin signaling. We also show that leaf venation and auxin‐mediated PIN repolarization in the root require TIR1/AFB signaling. Further studies based on this experimental system are likely to yield better understanding of the mechanisms underlying auxin transport polarization in other developmental contexts.}, author = {Mazur, E and Kulik, Ivan and Hajny, Jakub and Friml, Jiří}, issn = {1469-8137}, journal = {New Phytologist}, number = {5}, pages = {1375--1383}, publisher = {Wiley}, title = {{Auxin canalization and vascular tissue formation by TIR1/AFB-mediated auxin signaling in arabidopsis}}, doi = {10.1111/nph.16446}, volume = {226}, year = {2020}, } @phdthesis{8822, abstract = {Self-organization is a hallmark of plant development manifested e.g. by intricate leaf vein patterns, flexible formation of vasculature during organogenesis or its regeneration following wounding. Spontaneously arising channels transporting the phytohormone auxin, created by coordinated polar localizations of PIN-FORMED 1 (PIN1) auxin exporter, provide positional cues for these as well as other plant patterning processes. To find regulators acting downstream of auxin and the TIR1/AFB auxin signaling pathway essential for PIN1 coordinated polarization during auxin canalization, we performed microarray experiments. Besides the known components of general PIN polarity maintenance, such as PID and PIP5K kinases, we identified and characterized a new regulator of auxin canalization, the transcription factor WRKY DNA-BINDING PROTEIN 23 (WRKY23). Next, we designed a subsequent microarray experiment to further uncover other molecular players, downstream of auxin-TIR1/AFB-WRKY23 involved in the regulation of auxin-mediated PIN repolarization. We identified a novel and crucial part of the molecular machinery underlying auxin canalization. The auxin-regulated malectin-type receptor-like kinase CAMEL and the associated leucine-rich repeat receptor-like kinase CANAR target and directly phosphorylate PIN auxin transporters. camel and canar mutants are impaired in PIN1 subcellular trafficking and auxin-mediated repolarization leading to defects in auxin transport, ultimately to leaf venation and vasculature regeneration defects. Our results describe the CAMEL-CANAR receptor complex, which is required for auxin feed-back on its own transport and thus for coordinated tissue polarization during auxin canalization.}, author = {Hajny, Jakub}, issn = {2663-337X}, pages = {249}, publisher = {Institute of Science and Technology Austria}, title = {{Identification and characterization of the molecular machinery of auxin-dependent canalization during vasculature formation and regeneration}}, doi = {10.15479/AT:ISTA:8822}, year = {2020}, } @phdthesis{8350, abstract = {Cytoplasm is a gel-like crowded environment composed of tens of thousands of macromolecules, organelles, cytoskeletal networks and cytosol. The structure of the cytoplasm is thought to be highly organized and heterogeneous due to the crowding of its constituents and their effective compartmentalization. In such an environment, the diffusive dynamics of the molecules is very restricted, an effect that is further amplified by clustering and anchoring of molecules. Despite the jammed nature of the cytoplasm at the microscopic scale, large-scale reorganization of cytoplasm is essential for important cellular functions, such as nuclear positioning and cell division. How such mesoscale reorganization of the cytoplasm is achieved, especially for very large cells such as oocytes or syncytial tissues that can span hundreds of micrometers in size, has only begun to be understood. In this thesis, I focus on the recent advances in elucidating the molecular, cellular and biophysical principles underlying cytoplasmic organization across different scales, structures and species. First, I outline which of these principles have been identified by reductionist approaches, such as in vitro reconstitution assays, where boundary conditions and components can be modulated at ease. I then describe how the theoretical and experimental framework established in these reduced systems have been applied to their more complex in vivo counterparts, in particular oocytes and embryonic syncytial structures, and discuss how such complex biological systems can initiate symmetry breaking and establish patterning. Specifically, I examine an example of large-scale reorganizations taking place in zebrafish embryos, where extensive cytoplasmic streaming leads to the segregation of cytoplasm from yolk granules along the animal-vegetal axis of the embryo. Using biophysical experimentation and theory, I investigate the forces underlying this process, to show that this process does not rely on cortical actin reorganization, as previously thought, but instead on a cell-cycle-dependent bulk actin polymerization wave traveling from the animal to the vegetal pole of the embryo. This wave functions in segregation by both pulling cytoplasm animally and pushing yolk granules vegetally. Cytoplasm pulling is mediated by bulk actin network flows exerting friction forces on the cytoplasm, while yolk granule pushing is achieved by a mechanism closely resembling actin comet formation on yolk granules. This study defines a novel role of bulk actin polymerization waves in embryo polarization via cytoplasmic segregation. Lastly, I describe the cytoplasmic reorganizations taking place during zebrafish oocyte maturation, where the initial segregation of the cytoplasm and yolk granules occurs. Here, I demonstrate a previously uncharacterized wave of microtubule aster formation, traveling the oocyte along the animal-vegetal axis. Further research is required to determine the role of such microtubule structures in cytoplasmic reorganizations therein. Collectively, these studies provide further evidence for the coupling between cell cytoskeleton and cell cycle machinery, which can underlie a core self-organizing mechanism for orchestrating large-scale reorganizations in a cell-cycle-tunable manner, where the modulations of the force-generating machinery and cytoplasmic mechanics can be harbored to fulfill cellular functions.}, author = {Shamipour, Shayan}, issn = {2663-337X}, pages = {107}, publisher = {Institute of Science and Technology Austria}, title = {{Bulk actin dynamics drive phase segregation in zebrafish oocytes }}, doi = {10.15479/AT:ISTA:8350}, year = {2020}, } @article{8569, abstract = {Concerted radial migration of newly born cortical projection neurons, from their birthplace to their final target lamina, is a key step in the assembly of the cerebral cortex. The cellular and molecular mechanisms regulating the specific sequential steps of radial neuronal migration in vivo are however still unclear, let alone the effects and interactions with the extracellular environment. In any in vivo context, cells will always be exposed to a complex extracellular environment consisting of (1) secreted factors acting as potential signaling cues, (2) the extracellular matrix, and (3) other cells providing cell–cell interaction through receptors and/or direct physical stimuli. Most studies so far have described and focused mainly on intrinsic cell-autonomous gene functions in neuronal migration but there is accumulating evidence that non-cell-autonomous-, local-, systemic-, and/or whole tissue-wide effects substantially contribute to the regulation of radial neuronal migration. These non-cell-autonomous effects may differentially affect cortical neuron migration in distinct cellular environments. However, the cellular and molecular natures of such non-cell-autonomous mechanisms are mostly unknown. Furthermore, physical forces due to collective migration and/or community effects (i.e., interactions with surrounding cells) may play important roles in neocortical projection neuron migration. In this concise review, we first outline distinct models of non-cell-autonomous interactions of cortical projection neurons along their radial migration trajectory during development. We then summarize experimental assays and platforms that can be utilized to visualize and potentially probe non-cell-autonomous mechanisms. Lastly, we define key questions to address in the future.}, author = {Hansen, Andi H and Hippenmeyer, Simon}, issn = {2296-634X}, journal = {Frontiers in Cell and Developmental Biology}, number = {9}, publisher = {Frontiers}, title = {{Non-cell-autonomous mechanisms in radial projection neuron migration in the developing cerebral cortex}}, doi = {10.3389/fcell.2020.574382}, volume = {8}, year = {2020}, } @article{7815, abstract = {Beginning from a limited pool of progenitors, the mammalian cerebral cortex forms highly organized functional neural circuits. However, the underlying cellular and molecular mechanisms regulating lineage transitions of neural stem cells (NSCs) and eventual production of neurons and glia in the developing neuroepithelium remains unclear. Methods to trace NSC division patterns and map the lineage of clonally related cells have advanced dramatically. However, many contemporary lineage tracing techniques suffer from the lack of cellular resolution of progeny cell fate, which is essential for deciphering progenitor cell division patterns. Presented is a protocol using mosaic analysis with double markers (MADM) to perform in vivo clonal analysis. MADM concomitantly manipulates individual progenitor cells and visualizes precise division patterns and lineage progression at unprecedented single cell resolution. MADM-based interchromosomal recombination events during the G2-X phase of mitosis, together with temporally inducible CreERT2, provide exact information on the birth dates of clones and their division patterns. Thus, MADM lineage tracing provides unprecedented qualitative and quantitative optical readouts of the proliferation mode of stem cell progenitors at the single cell level. MADM also allows for examination of the mechanisms and functional requirements of candidate genes in NSC lineage progression. This method is unique in that comparative analysis of control and mutant subclones can be performed in the same tissue environment in vivo. Here, the protocol is described in detail, and experimental paradigms to employ MADM for clonal analysis and lineage tracing in the developing cerebral cortex are demonstrated. Importantly, this protocol can be adapted to perform MADM clonal analysis in any murine stem cell niche, as long as the CreERT2 driver is present.}, author = {Beattie, Robert J and Streicher, Carmen and Amberg, Nicole and Cheung, Giselle T and Contreras, Ximena and Hansen, Andi H and Hippenmeyer, Simon}, issn = {1940-087X}, journal = {Journal of Visual Experiments}, number = {159}, publisher = {MyJove Corporation}, title = {{Lineage tracing and clonal analysis in developing cerebral cortex using mosaic analysis with double markers (MADM)}}, doi = {10.3791/61147}, year = {2020}, } @phdthesis{7902, abstract = {Mosaic genetic analysis has been widely used in different model organisms such as the fruit fly to study gene-function in a cell-autonomous or tissue-specific fashion. More recently, and less easily conducted, mosaic genetic analysis in mice has also been enabled with the ambition to shed light on human gene function and disease. These genetic tools are of particular interest, but not restricted to, the study of the brain. Notably, the MADM technology offers a genetic approach in mice to visualize and concomitantly manipulate small subsets of genetically defined cells at a clonal level and single cell resolution. MADM-based analysis has already advanced the study of genetic mechanisms regulating brain development and is expected that further MADM-based analysis of genetic alterations will continue to reveal important insights on the fundamental principles of development and disease to potentially assist in the development of new therapies or treatments. In summary, this work completed and characterized the necessary genome-wide genetic tools to perform MADM-based analysis at single cell level of the vast majority of mouse genes in virtually any cell type and provided a protocol to perform lineage tracing using the novel MADM resource. Importantly, this work also explored and revealed novel aspects of biologically relevant events in an in vivo context, such as the chromosome-specific bias of chromatid sister segregation pattern, the generation of cell-type diversity in the cerebral cortex and in the cerebellum and finally, the relevance of the interplay between the cell-autonomous gene function and cell-non-autonomous (community) effects in radial glial progenitor lineage progression. This work provides a foundation and opens the door to further elucidating the molecular mechanisms underlying neuronal diversity and astrocyte generation.}, author = {Contreras, Ximena}, issn = {2663-337X}, pages = {214}, publisher = {Institute of Science and Technology Austria}, title = {{Genetic dissection of neural development in health and disease at single cell resolution}}, doi = {10.15479/AT:ISTA:7902}, year = {2020}, } @article{8190, author = {Sixt, Michael K and Huttenlocher, Anna}, issn = {1540-8140}, journal = {The Journal of Cell Biology}, number = {8}, publisher = {Rockefeller University Press}, title = {{Zena Werb (1945-2020): Cell biology in context}}, doi = {10.1083/jcb.202007029}, volume = {219}, year = {2020}, } @article{8986, abstract = {Flowering plants display the highest diversity among plant species and have notably shaped terrestrial landscapes. Nonetheless, the evolutionary origin of their unprecedented morphological complexity remains largely an enigma. Here, we show that the coevolution of cis-regulatory and coding regions of PIN-FORMED (PIN) auxin transporters confined their expression to certain cell types and directed their subcellular localization to particular cell sides, which together enabled dynamic auxin gradients across tissues critical to the complex architecture of flowering plants. Extensive intraspecies and interspecies genetic complementation experiments with PINs from green alga up to flowering plant lineages showed that PIN genes underwent three subsequent, critical evolutionary innovations and thus acquired a triple function to regulate the development of three essential components of the flowering plant Arabidopsis: shoot/root, inflorescence, and floral organ. Our work highlights the critical role of functional innovations within the PIN gene family as essential prerequisites for the origin of flowering plants.}, author = {Zhang, Yuzhou and Rodriguez Solovey, Lesia and Li, Lanxin and Zhang, Xixi and Friml, Jiří}, issn = {2375-2548}, journal = {Science Advances}, number = {50}, publisher = {AAAS}, title = {{Functional innovations of PIN auxin transporters mark crucial evolutionary transitions during rise of flowering plants}}, doi = {10.1126/sciadv.abc8895}, volume = {6}, year = {2020}, } @article{8283, abstract = {Drought and salt stress are the main environmental cues affecting the survival, development, distribution, and yield of crops worldwide. MYB transcription factors play a crucial role in plants’ biological processes, but the function of pineapple MYB genes is still obscure. In this study, one of the pineapple MYB transcription factors, AcoMYB4, was isolated and characterized. The results showed that AcoMYB4 is localized in the cell nucleus, and its expression is induced by low temperature, drought, salt stress, and hormonal stimulation, especially by abscisic acid (ABA). Overexpression of AcoMYB4 in rice and Arabidopsis enhanced plant sensitivity to osmotic stress; it led to an increase in the number stomata on leaf surfaces and lower germination rate under salt and drought stress. Furthermore, in AcoMYB4 OE lines, the membrane oxidation index, free proline, and soluble sugar contents were decreased. In contrast, electrolyte leakage and malondialdehyde (MDA) content increased significantly due to membrane injury, indicating higher sensitivity to drought and salinity stresses. Besides the above, both the expression level and activities of several antioxidant enzymes were decreased, indicating lower antioxidant activity in AcoMYB4 transgenic plants. Moreover, under osmotic stress, overexpression of AcoMYB4 inhibited ABA biosynthesis through a decrease in the transcription of genes responsible for ABA synthesis (ABA1 and ABA2) and ABA signal transduction factor ABI5. These results suggest that AcoMYB4 negatively regulates osmotic stress by attenuating cellular ABA biosynthesis and signal transduction pathways. }, author = {Chen, Huihuang and Lai, Linyi and Li, Lanxin and Liu, Liping and Jakada, Bello Hassan and Huang, Youmei and He, Qing and Chai, Mengnan and Niu, Xiaoping and Qin, Yuan}, issn = {14220067}, journal = {International Journal of Molecular Sciences}, number = {16}, publisher = {MDPI}, title = {{AcoMYB4, an Ananas comosus L. MYB transcription factor, functions in osmotic stress through negative regulation of ABA signaling}}, doi = {10.3390/ijms21165727}, volume = {21}, year = {2020}, } @article{8139, abstract = {Clathrin-mediated endocytosis (CME) is a crucial cellular process implicated in many aspects of plant growth, development, intra- and inter-cellular signaling, nutrient uptake and pathogen defense. Despite these significant roles, little is known about the precise molecular details of how it functions in planta. In order to facilitate the direct quantitative study of plant CME, here we review current routinely used methods and present refined, standardized quantitative imaging protocols which allow the detailed characterization of CME at multiple scales in plant tissues. These include: (i) an efficient electron microscopy protocol for the imaging of Arabidopsis CME vesicles in situ, thus providing a method for the detailed characterization of the ultra-structure of clathrin-coated vesicles; (ii) a detailed protocol and analysis for quantitative live-cell fluorescence microscopy to precisely examine the temporal interplay of endocytosis components during single CME events; (iii) a semi-automated analysis to allow the quantitative characterization of global internalization of cargos in whole plant tissues; and (iv) an overview and validation of useful genetic and pharmacological tools to interrogate the molecular mechanisms and function of CME in intact plant samples.}, author = {Johnson, Alexander J and Gnyliukh, Nataliia and Kaufmann, Walter and Narasimhan, Madhumitha and Vert, G and Bednarek, SY and Friml, Jiří}, issn = {1477-9137}, journal = {Journal of Cell Science}, number = {15}, publisher = {The Company of Biologists}, title = {{Experimental toolbox for quantitative evaluation of clathrin-mediated endocytosis in the plant model Arabidopsis}}, doi = {10.1242/jcs.248062}, volume = {133}, year = {2020}, } @article{9160, abstract = {Auxin is a key hormonal regulator, that governs plant growth and development in concert with other hormonal pathways. The unique feature of auxin is its polar, cell-to-cell transport that leads to the formation of local auxin maxima and gradients, which coordinate initiation and patterning of plant organs. The molecular machinery mediating polar auxin transport is one of the important points of interaction with other hormones. Multiple hormonal pathways converge at the regulation of auxin transport and form a regulatory network that integrates various developmental and environmental inputs to steer plant development. In this review, we discuss recent advances in understanding the mechanisms that underlie regulation of polar auxin transport by multiple hormonal pathways. Specifically, we focus on the post-translational mechanisms that contribute to fine-tuning of the abundance and polarity of auxin transporters at the plasma membrane and thereby enable rapid modification of the auxin flow to coordinate plant growth and development.}, author = {Semeradova, Hana and Montesinos López, Juan C and Benková, Eva}, issn = {2590-3462}, journal = {Plant Communications}, number = {3}, publisher = {Elsevier}, title = {{All roads lead to auxin: Post-translational regulation of auxin transport by multiple hormonal pathways}}, doi = {10.1016/j.xplc.2020.100048}, volume = {1}, year = {2020}, } @inproceedings{10877, abstract = {This report presents the results of a friendly competition for formal verification of continuous and hybrid systems with piecewise constant dynamics. The friendly competition took place as part of the workshop Applied Verification for Continuous and Hybrid Systems (ARCH) in 2019. In this third edition, six tools have been applied to solve five different benchmark problems in the category for piecewise constant dynamics: BACH, Lyse, Hy- COMP, PHAVer/SX, PHAVerLite, and VeriSiMPL. Compared to last year, a new tool has participated (HyCOMP) and PHAVerLite has replaced PHAVer-lite. The result is a snap- shot of the current landscape of tools and the types of benchmarks they are particularly suited for. Due to the diversity of problems, we are not ranking tools, yet the presented results probably provide the most complete assessment of tools for the safety verification of continuous and hybrid systems with piecewise constant dynamics up to this date.}, author = {Frehse, Goran and Abate, Alessandro and Adzkiya, Dieky and Becchi, Anna and Bu, Lei and Cimatti, Alessandro and Giacobbe, Mirco and Griggio, Alberto and Mover, Sergio and Mufid, Muhammad Syifa'ul and Riouak, Idriss and Tonetta, Stefano and Zaffanella, Enea}, booktitle = {ARCH19. 6th International Workshop on Applied Verification of Continuous and Hybrid Systems}, editor = {Frehse, Goran and Althoff, Matthias}, issn = {2398-7340}, location = {Montreal, Canada}, pages = {1--13}, publisher = {EasyChair}, title = {{ARCH-COMP19 Category Report: Hybrid systems with piecewise constant dynamics}}, doi = {10.29007/rjwn}, volume = {61}, year = {2019}, } @article{441, author = {Kalinin, Nikita and Shkolnikov, Mikhail}, issn = {2199-6768}, journal = {European Journal of Mathematics}, number = {3}, pages = {909–928}, publisher = {Springer Nature}, title = {{Tropical formulae for summation over a part of SL(2,Z)}}, doi = {10.1007/s40879-018-0218-0}, volume = {5}, year = {2019}, } @inbook{5793, abstract = {The transcription coactivator, Yes-associated protein (YAP), which is a nuclear effector of the Hippo signaling pathway, has been shown to be a mechano-transducer. By using mutant fish and human 3D spheroids, we have recently demonstrated that YAP is also a mechano-effector. YAP functions in three-dimensional (3D) morphogenesis of organ and global body shape by controlling actomyosin-mediated tissue tension. In this chapter, we present a platform that links the findings in fish embryos with human cells. The protocols for analyzing tissue tension-mediated global body shape/organ morphogenesis in vivo and ex vivo using medaka fish embryos and in vitro using human cell spheroids represent useful tools for unraveling the molecular mechanisms by which YAP functions in regulating global body/organ morphogenesis.}, author = {Asaoka, Yoichi and Morita, Hitoshi and Furumoto, Hiroko and Heisenberg, Carl-Philipp J and Furutani-Seiki, Makoto}, booktitle = {The hippo pathway}, editor = {Hergovich, Alexander}, isbn = {978-1-4939-8909-6}, pages = {167--181}, publisher = {Springer}, title = {{Studying YAP-mediated 3D morphogenesis using fish embryos and human spheroids}}, doi = {10.1007/978-1-4939-8910-2_14}, volume = {1893}, year = {2019}, } @article{5887, abstract = {Cryptographic security is usually defined as a guarantee that holds except when a bad event with negligible probability occurs, and nothing is guaranteed in that bad case. However, in settings where such failure can happen with substantial probability, one needs to provide guarantees even for the bad case. A typical example is where a (possibly weak) password is used instead of a secure cryptographic key to protect a session, the bad event being that the adversary correctly guesses the password. In a situation with multiple such sessions, a per-session guarantee is desired: any session for which the password has not been guessed remains secure, independently of whether other sessions have been compromised. A new formalism for stating such gracefully degrading security guarantees is introduced and applied to analyze the examples of password-based message authentication and password-based encryption. While a natural per-message guarantee is achieved for authentication, the situation of password-based encryption is more delicate: a per-session confidentiality guarantee only holds against attackers for which the distribution of password-guessing effort over the sessions is known in advance. In contrast, for more general attackers without such a restriction, a strong, composable notion of security cannot be achieved.}, author = {Demay, Gregory and Gazi, Peter and Maurer, Ueli and Tackmann, Bjorn}, issn = {0926227X}, journal = {Journal of Computer Security}, number = {1}, pages = {75--111}, publisher = {IOS Press}, title = {{Per-session security: Password-based cryptography revisited}}, doi = {10.3233/JCS-181131}, volume = {27}, year = {2019}, } @article{6515, abstract = {We give non-degeneracy criteria for Riemannian simplices based on simplices in spaces of constant sectional curvature. It extends previous work on Riemannian simplices, where we developed Riemannian simplices with respect to Euclidean reference simplices. The criteria we give in this article are in terms of quality measures for spaces of constant curvature that we develop here. We see that simplices in spaces that have nearly constant curvature, are already non-degenerate under very weak quality demands. This is of importance because it allows for sampling of Riemannian manifolds based on anisotropy of the manifold and not (absolute) curvature.}, author = {Dyer, Ramsay and Vegter, Gert and Wintraecken, Mathijs}, issn = {1920-180X}, journal = {Journal of Computational Geometry }, number = {1}, pages = {223–256}, publisher = {Carleton University}, title = {{Simplices modelled on spaces of constant curvature}}, doi = {10.20382/jocg.v10i1a9}, volume = {10}, year = {2019}, } @inproceedings{6528, abstract = {We construct a verifiable delay function (VDF) by showing how the Rivest-Shamir-Wagner time-lock puzzle can be made publicly verifiable. Concretely, we give a statistically sound public-coin protocol to prove that a tuple (N,x,T,y) satisfies y=x2T (mod N) where the prover doesn’t know the factorization of N and its running time is dominated by solving the puzzle, that is, compute x2T, which is conjectured to require T sequential squarings. To get a VDF we make this protocol non-interactive using the Fiat-Shamir heuristic.The motivation for this work comes from the Chia blockchain design, which uses a VDF as akey ingredient. For typical parameters (T≤2 40, N= 2048), our proofs are of size around 10K B, verification cost around three RSA exponentiations and computing the proof is 8000 times faster than solving the puzzle even without any parallelism.}, author = {Pietrzak, Krzysztof Z}, booktitle = {10th Innovations in Theoretical Computer Science Conference}, isbn = {978-3-95977-095-8}, issn = {1868-8969}, location = {San Diego, CA, United States}, publisher = {Schloss Dagstuhl - Leibniz-Zentrum für Informatik}, title = {{Simple verifiable delay functions}}, doi = {10.4230/LIPICS.ITCS.2019.60}, volume = {124}, year = {2019}, } @inproceedings{6565, abstract = {In this paper, we address the problem of synthesizing periodic switching controllers for stabilizing a family of linear systems. Our broad approach consists of constructing a finite game graph based on the family of linear systems such that every winning strategy on the game graph corresponds to a stabilizing switching controller for the family of linear systems. The construction of a (finite) game graph, the synthesis of a winning strategy and the extraction of a stabilizing controller are all computationally feasible. We illustrate our method on an example.}, author = {Kundu, Atreyee and Garcia Soto, Miriam and Prabhakar, Pavithra}, booktitle = {5th Indian Control Conference Proceedings}, isbn = {978-153866246-5}, location = {Delhi, India}, publisher = {IEEE}, title = {{Formal synthesis of stabilizing controllers for periodically controlled linear switched systems}}, doi = {10.1109/INDIANCC.2019.8715598}, year = {2019}, } @inproceedings{6628, abstract = {Fejes Tóth [5] and Schneider [9] studied approximations of smooth convex hypersurfaces in Euclidean space by piecewise flat triangular meshes with a given number of vertices on the hypersurface that are optimal with respect to Hausdorff distance. They proved that this Hausdorff distance decreases inversely proportional with m 2/(d−1), where m is the number of vertices and d is the dimension of Euclidean space. Moreover the pro-portionality constant can be expressed in terms of the Gaussian curvature, an intrinsic quantity. In this short note, we prove the extrinsic nature of this constant for manifolds of sufficiently high codimension. We do so by constructing an family of isometric embeddings of the flat torus in Euclidean space.}, author = {Vegter, Gert and Wintraecken, Mathijs}, booktitle = {The 31st Canadian Conference in Computational Geometry}, location = {Edmonton, Canada}, pages = {275--279}, title = {{The extrinsic nature of the Hausdorff distance of optimal triangulations of manifolds}}, year = {2019}, } @inproceedings{6648, abstract = {Various kinds of data are routinely represented as discrete probability distributions. Examples include text documents summarized by histograms of word occurrences and images represented as histograms of oriented gradients. Viewing a discrete probability distribution as a point in the standard simplex of the appropriate dimension, we can understand collections of such objects in geometric and topological terms. Importantly, instead of using the standard Euclidean distance, we look into dissimilarity measures with information-theoretic justification, and we develop the theory needed for applying topological data analysis in this setting. In doing so, we emphasize constructions that enable the usage of existing computational topology software in this context.}, author = {Edelsbrunner, Herbert and Virk, Ziga and Wagner, Hubert}, booktitle = {35th International Symposium on Computational Geometry}, isbn = {9783959771047}, location = {Portland, OR, United States}, pages = {31:1--31:14}, publisher = {Schloss Dagstuhl - Leibniz-Zentrum für Informatik}, title = {{Topological data analysis in information space}}, doi = {10.4230/LIPICS.SOCG.2019.31}, volume = {129}, year = {2019}, } @article{6659, abstract = {Chemical labeling of proteins with synthetic molecular probes offers the possibility to probe the functions of proteins of interest in living cells. However, the methods for covalently labeling targeted proteins using complementary peptide tag-probe pairs are still limited, irrespective of the versatility of such pairs in biological research. Herein, we report the new CysHis tag-Ni(II) probe pair for the specific covalent labeling of proteins. A broad-range evaluation of the reactivity profiles of the probe and the CysHis peptide tag afforded a tag-probe pair with an optimized and high labeling selectivity and reactivity. In particular, the labeling specificity of this pair was notably improved compared to the previously reported one. This pair was successfully utilized for the fluorescence imaging of membrane proteins on the surfaces of living cells, demonstrating its potential utility in biological research.}, author = {Zenmyo, Naoki and Tokumaru, Hiroki and Uchinomiya, Shohei and Fuchida, Hirokazu and Tabata, Shigekazu and Hamachi, Itaru and Shigemoto, Ryuichi and Ojida, Akio}, issn = {00092673}, journal = {Bulletin of the Chemical Society of Japan}, number = {5}, pages = {995--1000}, publisher = {Bulletin of the Chemical Society of Japan}, title = {{Optimized reaction pair of the CysHis tag and Ni(II)-NTA probe for highly selective chemical labeling of membrane proteins}}, doi = {10.1246/bcsj.20190034}, volume = {92}, year = {2019}, } @inproceedings{6725, abstract = {A Valued Constraint Satisfaction Problem (VCSP) provides a common framework that can express a wide range of discrete optimization problems. A VCSP instance is given by a finite set of variables, a finite domain of labels, and an objective function to be minimized. This function is represented as a sum of terms where each term depends on a subset of the variables. To obtain different classes of optimization problems, one can restrict all terms to come from a fixed set Γ of cost functions, called a language. Recent breakthrough results have established a complete complexity classification of such classes with respect to language Γ: if all cost functions in Γ satisfy a certain algebraic condition then all Γ-instances can be solved in polynomial time, otherwise the problem is NP-hard. Unfortunately, testing this condition for a given language Γ is known to be NP-hard. We thus study exponential algorithms for this meta-problem. We show that the tractability condition of a finite-valued language Γ can be tested in O(3‾√3|D|⋅poly(size(Γ))) time, where D is the domain of Γ and poly(⋅) is some fixed polynomial. We also obtain a matching lower bound under the Strong Exponential Time Hypothesis (SETH). More precisely, we prove that for any constant δ<1 there is no O(3‾√3δ|D|) algorithm, assuming that SETH holds.}, author = {Kolmogorov, Vladimir}, booktitle = {46th International Colloquium on Automata, Languages and Programming}, isbn = {978-3-95977-109-2}, issn = {1868-8969}, location = {Patras, Greece}, pages = {77:1--77:12}, publisher = {Schloss Dagstuhl - Leibniz-Zentrum für Informatik}, title = {{Testing the complexity of a valued CSP language}}, doi = {10.4230/LIPICS.ICALP.2019.77}, volume = {132}, year = {2019}, } @inbook{6726, abstract = {Randomness is an essential part of any secure cryptosystem, but many constructions rely on distributions that are not uniform. This is particularly true for lattice based cryptosystems, which more often than not make use of discrete Gaussian distributions over the integers. For practical purposes it is crucial to evaluate the impact that approximation errors have on the security of a scheme to provide the best possible trade-off between security and performance. Recent years have seen surprising results allowing to use relatively low precision while maintaining high levels of security. A key insight in these results is that sampling a distribution with low relative error can provide very strong security guarantees. Since floating point numbers provide guarantees on the relative approximation error, they seem a suitable tool in this setting, but it is not obvious which sampling algorithms can actually profit from them. While previous works have shown that inversion sampling can be adapted to provide a low relative error (Pöppelmann et al., CHES 2014; Prest, ASIACRYPT 2017), other works have called into question if this is possible for other sampling techniques (Zheng et al., Eprint report 2018/309). In this work, we consider all sampling algorithms that are popular in the cryptographic setting and analyze the relationship of floating point precision and the resulting relative error. We show that all of the algorithms either natively achieve a low relative error or can be adapted to do so.}, author = {Walter, Michael}, booktitle = {Progress in Cryptology – AFRICACRYPT 2019}, editor = {Buchmann, J and Nitaj, A and Rachidi, T}, isbn = {978-3-0302-3695-3}, issn = {0302-9743}, location = {Rabat, Morocco}, pages = {157--180}, publisher = {Springer Nature}, title = {{Sampling the integers with low relative error}}, doi = {10.1007/978-3-030-23696-0_9}, volume = {11627}, year = {2019}, } @article{6750, abstract = {Polar codes have gained extensive attention during the past few years and recently they have been selected for the next generation of wireless communications standards (5G). Successive-cancellation-based (SC-based) decoders, such as SC list (SCL) and SC flip (SCF), provide a reasonable error performance for polar codes at the cost of low decoding speed. Fast SC-based decoders, such as Fast-SSC, Fast-SSCL, and Fast-SSCF, identify the special constituent codes in a polar code graph off-line, produce a list of operations, store the list in memory, and feed the list to the decoder to decode the constituent codes in order efficiently, thus increasing the decoding speed. However, the list of operations is dependent on the code rate and as the rate changes, a new list is produced, making fast SC-based decoders not rate-flexible. In this paper, we propose a completely rate-flexible fast SC-based decoder by creating the list of operations directly in hardware, with low implementation complexity. We further propose a hardware architecture implementing the proposed method and show that the area occupation of the rate-flexible fast SC-based decoder in this paper is only 38% of the total area of the memory-based base-line decoder when 5G code rates are supported. }, author = {Hashemi, Seyyed Ali and Condo, Carlo and Mondelli, Marco and Gross, Warren J}, issn = {1053587X}, journal = {IEEE Transactions on Signal Processing}, number = {22}, publisher = {IEEE}, title = {{Rate-flexible fast polar decoders}}, doi = {10.1109/TSP.2019.2944738}, volume = {67}, year = {2019}, } @article{6759, abstract = {We consider the graph class Grounded-L corresponding to graphs that admit an intersection representation by L-shaped curves, where additionally the topmost points of each curve are assumed to belong to a common horizontal line. We prove that Grounded-L graphs admit an equivalent characterisation in terms of vertex ordering with forbidden patterns. We also compare this class to related intersection classes, such as the grounded segment graphs, the monotone L-graphs (a.k.a. max point-tolerance graphs), or the outer-1-string graphs. We give constructions showing that these classes are all distinct and satisfy only trivial or previously known inclusions.}, author = {Jelínek, Vít and Töpfer, Martin}, issn = {10778926}, journal = {Electronic Journal of Combinatorics}, number = {3}, publisher = {Electronic Journal of Combinatorics}, title = {{On grounded L-graphs and their relatives}}, doi = {10.37236/8096}, volume = {26}, year = {2019}, } @inproceedings{6822, abstract = {In two-player games on graphs, the players move a token through a graph to produce an infinite path, which determines the qualitative winner or quantitative payoff of the game. In bidding games, in each turn, we hold an auction between the two players to determine which player moves the token. Bidding games have largely been studied with concrete bidding mechanisms that are variants of a first-price auction: in each turn both players simultaneously submit bids, the higher bidder moves the token, and pays his bid to the lower bidder in Richman bidding, to the bank in poorman bidding, and in taxman bidding, the bid is split between the other player and the bank according to a predefined constant factor. Bidding games are deterministic games. They have an intriguing connection with a fragment of stochastic games called randomturn games. We study, for the first time, a combination of bidding games with probabilistic behavior; namely, we study bidding games that are played on Markov decision processes, where the players bid for the right to choose the next action, which determines the probability distribution according to which the next vertex is chosen. We study parity and meanpayoff bidding games on MDPs and extend results from the deterministic bidding setting to the probabilistic one.}, author = {Avni, Guy and Henzinger, Thomas A and Ibsen-Jensen, Rasmus and Novotny, Petr}, booktitle = { Proceedings of the 13th International Conference of Reachability Problems}, isbn = {978-303030805-6}, issn = {0302-9743}, location = {Brussels, Belgium}, pages = {1--12}, publisher = {Springer}, title = {{Bidding games on Markov decision processes}}, doi = {10.1007/978-3-030-30806-3_1}, volume = {11674}, year = {2019}, } @inproceedings{6887, abstract = {The fundamental model-checking problem, given as input a model and a specification, asks for the algorithmic verification of whether the model satisfies the specification. Two classical models for reactive systems are graphs and Markov decision processes (MDPs). A basic specification formalism in the verification of reactive systems is the strong fairness (aka Streett) objective, where given different types of requests and corresponding grants, the requirement is that for each type, if the request event happens infinitely often, then the corresponding grant event must also happen infinitely often. All omega-regular objectives can be expressed as Streett objectives and hence they are canonical in verification. Consider graphs/MDPs with n vertices, m edges, and a Streett objectives with k pairs, and let b denote the size of the description of the Streett objective for the sets of requests and grants. The current best-known algorithm for the problem requires time O(min(n^2, m sqrt{m log n}) + b log n). In this work we present randomized near-linear time algorithms, with expected running time O~(m + b), where the O~ notation hides poly-log factors. Our randomized algorithms are near-linear in the size of the input, and hence optimal up to poly-log factors. }, author = {Chatterjee, Krishnendu and Dvorák, Wolfgang and Henzinger, Monika H and Svozil, Alexander}, booktitle = {Leibniz International Proceedings in Informatics}, location = {Amsterdam, Netherlands}, publisher = {Schloss Dagstuhl - Leibniz-Zentrum für Informatik}, title = {{Near-linear time algorithms for Streett objectives in graphs and MDPs}}, doi = {10.4230/LIPICS.CONCUR.2019.7}, volume = {140}, year = {2019}, } @inproceedings{6888, abstract = {In this paper, we design novel liquid time-constant recurrent neural networks for robotic control, inspired by the brain of the nematode, C. elegans. In the worm's nervous system, neurons communicate through nonlinear time-varying synaptic links established amongst them by their particular wiring structure. This property enables neurons to express liquid time-constants dynamics and therefore allows the network to originate complex behaviors with a small number of neurons. We identify neuron-pair communication motifs as design operators and use them to configure compact neuronal network structures to govern sequential robotic tasks. The networks are systematically designed to map the environmental observations to motor actions, by their hierarchical topology from sensory neurons, through recurrently-wired interneurons, to motor neurons. The networks are then parametrized in a supervised-learning scheme by a search-based algorithm. We demonstrate that obtained networks realize interpretable dynamics. We evaluate their performance in controlling mobile and arm robots, and compare their attributes to other artificial neural network-based control agents. Finally, we experimentally show their superior resilience to environmental noise, compared to the existing machine learning-based methods.}, author = {Lechner, Mathias and Hasani, Ramin and Zimmer, Manuel and Henzinger, Thomas A and Grosu, Radu}, booktitle = {Proceedings - IEEE International Conference on Robotics and Automation}, isbn = {9781538660270}, location = {Montreal, QC, Canada}, publisher = {IEEE}, title = {{Designing worm-inspired neural networks for interpretable robotic control}}, doi = {10.1109/icra.2019.8793840}, volume = {2019-May}, year = {2019}, } @inproceedings{6886, abstract = {In two-player games on graphs, the players move a token through a graph to produce an infinite path, which determines the winner of the game. Such games are central in formal methods since they model the interaction between a non-terminating system and its environment. In bidding games the players bid for the right to move the token: in each round, the players simultaneously submit bids, and the higher bidder moves the token and pays the other player. Bidding games are known to have a clean and elegant mathematical structure that relies on the ability of the players to submit arbitrarily small bids. Many applications, however, require a fixed granularity for the bids, which can represent, for example, the monetary value expressed in cents. We study, for the first time, the combination of discrete-bidding and infinite-duration games. Our most important result proves that these games form a large determined subclass of concurrent games, where determinacy is the strong property that there always exists exactly one player who can guarantee winning the game. In particular, we show that, in contrast to non-discrete bidding games, the mechanism with which tied bids are resolved plays an important role in discrete-bidding games. We study several natural tie-breaking mechanisms and show that, while some do not admit determinacy, most natural mechanisms imply determinacy for every pair of initial budgets. }, author = {Aghajohari, Milad and Avni, Guy and Henzinger, Thomas A}, location = {Amsterdam, Netherlands}, publisher = {Schloss Dagstuhl - Leibniz-Zentrum für Informatik}, title = {{Determinacy in discrete-bidding infinite-duration games}}, doi = {10.4230/LIPICS.CONCUR.2019.20}, volume = {140}, year = {2019}, } @inproceedings{6885, abstract = {A vector addition system with states (VASS) consists of a finite set of states and counters. A configuration is a state and a value for each counter; a transition changes the state and each counter is incremented, decremented, or left unchanged. While qualitative properties such as state and configuration reachability have been studied for VASS, we consider the long-run average cost of infinite computations of VASS. The cost of a configuration is for each state, a linear combination of the counter values. In the special case of uniform cost functions, the linear combination is the same for all states. The (regular) long-run emptiness problem is, given a VASS, a cost function, and a threshold value, if there is a (lasso-shaped) computation such that the long-run average value of the cost function does not exceed the threshold. For uniform cost functions, we show that the regular long-run emptiness problem is (a) decidable in polynomial time for integer-valued VASS, and (b) decidable but nonelementarily hard for natural-valued VASS (i.e., nonnegative counters). For general cost functions, we show that the problem is (c) NP-complete for integer-valued VASS, and (d) undecidable for natural-valued VASS. Our most interesting result is for (c) integer-valued VASS with general cost functions, where we establish a connection between the regular long-run emptiness problem and quadratic Diophantine inequalities. The general (nonregular) long-run emptiness problem is equally hard as the regular problem in all cases except (c), where it remains open. }, author = {Chatterjee, Krishnendu and Henzinger, Thomas A and Otop, Jan}, location = {Amsterdam, Netherlands}, publisher = {Schloss Dagstuhl - Leibniz-Zentrum für Informatik}, title = {{Long-run average behavior of vector addition systems with states}}, doi = {10.4230/LIPICS.CONCUR.2019.27}, volume = {140}, year = {2019}, } @inproceedings{6889, abstract = {We study Markov decision processes and turn-based stochastic games with parity conditions. There are three qualitative winning criteria, namely, sure winning, which requires all paths to satisfy the condition, almost-sure winning, which requires the condition to be satisfied with probability 1, and limit-sure winning, which requires the condition to be satisfied with probability arbitrarily close to 1. We study the combination of two of these criteria for parity conditions, e.g., there are two parity conditions one of which must be won surely, and the other almost-surely. The problem has been studied recently by Berthon et al. for MDPs with combination of sure and almost-sure winning, under infinite-memory strategies, and the problem has been established to be in NP cap co-NP. Even in MDPs there is a difference between finite-memory and infinite-memory strategies. Our main results for combination of sure and almost-sure winning are as follows: (a) we show that for MDPs with finite-memory strategies the problem is in NP cap co-NP; (b) we show that for turn-based stochastic games the problem is co-NP-complete, both for finite-memory and infinite-memory strategies; and (c) we present algorithmic results for the finite-memory case, both for MDPs and turn-based stochastic games, by reduction to non-stochastic parity games. In addition we show that all the above complexity results also carry over to combination of sure and limit-sure winning, and results for all other combinations can be derived from existing results in the literature. Thus we present a complete picture for the study of combinations of two qualitative winning criteria for parity conditions in MDPs and turn-based stochastic games. }, author = {Chatterjee, Krishnendu and Piterman, Nir}, location = {Amsterdam, Netherlands}, publisher = {Schloss Dagstuhl - Leibniz-Zentrum für Informatik}, title = {{Combinations of Qualitative Winning for Stochastic Parity Games}}, doi = {10.4230/LIPICS.CONCUR.2019.6}, volume = {140}, year = {2019}, } @inproceedings{6931, abstract = {Consider a distributed system with n processors out of which f can be Byzantine faulty. In the approximate agreement task, each processor i receives an input value xi and has to decide on an output value yi such that 1. the output values are in the convex hull of the non-faulty processors’ input values, 2. the output values are within distance d of each other. Classically, the values are assumed to be from an m-dimensional Euclidean space, where m ≥ 1. In this work, we study the task in a discrete setting, where input values with some structure expressible as a graph. Namely, the input values are vertices of a finite graph G and the goal is to output vertices that are within distance d of each other in G, but still remain in the graph-induced convex hull of the input values. For d = 0, the task reduces to consensus and cannot be solved with a deterministic algorithm in an asynchronous system even with a single crash fault. For any d ≥ 1, we show that the task is solvable in asynchronous systems when G is chordal and n > (ω + 1)f, where ω is the clique number of G. In addition, we give the first Byzantine-tolerant algorithm for a variant of lattice agreement. For synchronous systems, we show tight resilience bounds for the exact variants of these and related tasks over a large class of combinatorial structures.}, author = {Nowak, Thomas and Rybicki, Joel}, booktitle = {33rd International Symposium on Distributed Computing}, keywords = {consensus, approximate agreement, Byzantine faults, chordal graphs, lattice agreement}, location = {Budapest, Hungary}, pages = {29:1----29:17}, publisher = {Schloss Dagstuhl - Leibniz-Zentrum für Informatik}, title = {{Byzantine approximate agreement on graphs}}, doi = {10.4230/LIPICS.DISC.2019.29}, volume = {146}, year = {2019}, } @inproceedings{6985, abstract = {In this paper, we introduce a novel method to interpret recurrent neural networks (RNNs), particularly long short-term memory networks (LSTMs) at the cellular level. We propose a systematic pipeline for interpreting individual hidden state dynamics within the network using response characterization methods. The ranked contribution of individual cells to the network's output is computed by analyzing a set of interpretable metrics of their decoupled step and sinusoidal responses. As a result, our method is able to uniquely identify neurons with insightful dynamics, quantify relationships between dynamical properties and test accuracy through ablation analysis, and interpret the impact of network capacity on a network's dynamical distribution. Finally, we demonstrate the generalizability and scalability of our method by evaluating a series of different benchmark sequential datasets.}, author = {Hasani, Ramin and Amini, Alexander and Lechner, Mathias and Naser, Felix and Grosu, Radu and Rus, Daniela}, booktitle = {Proceedings of the International Joint Conference on Neural Networks}, isbn = {9781728119854}, location = {Budapest, Hungary}, publisher = {IEEE}, title = {{Response characterization for auditing cell dynamics in long short-term memory networks}}, doi = {10.1109/ijcnn.2019.8851954}, year = {2019}, } @article{7007, abstract = {We consider the primitive relay channel, where the source sends a message to the relay and to the destination, and the relay helps the communication by transmitting an additional message to the destination via a separate channel. Two well-known coding techniques have been introduced for this setting: decode-and-forward and compress-and-forward. In decode-and-forward, the relay completely decodes the message and sends some information to the destination; in compress-and-forward, the relay does not decode, and it sends a compressed version of the received signal to the destination using Wyner–Ziv coding. In this paper, we present a novel coding paradigm that provides an improved achievable rate for the primitive relay channel. The idea is to combine compress-and-forward and decode-and-forward via a chaining construction. We transmit over pairs of blocks: in the first block, we use compress-and-forward; and, in the second block, we use decode-and-forward. More specifically, in the first block, the relay does not decode, it compresses the received signal via Wyner–Ziv, and it sends only part of the compression to the destination. In the second block, the relay completely decodes the message, it sends some information to the destination, and it also sends the remaining part of the compression coming from the first block. By doing so, we are able to strictly outperform both compress-and-forward and decode-and-forward. Note that the proposed coding scheme can be implemented with polar codes. As such, it has the typical attractive properties of polar coding schemes, namely, quasi-linear encoding and decoding complexity, and error probability that decays at super-polynomial speed. As a running example, we take into account the special case of the erasure relay channel, and we provide a comparison between the rates achievable by our proposed scheme and the existing upper and lower bounds.}, author = {Mondelli, Marco and Hassani, S. Hamed and Urbanke, Rüdiger}, issn = {1999-4893}, journal = {Algorithms}, number = {10}, publisher = {MDPI}, title = {{A new coding paradigm for the primitive relay channel}}, doi = {10.3390/a12100218}, volume = {12}, year = {2019}, } @inproceedings{7035, abstract = {The aim of this short note is to expound one particular issue that was discussed during the talk [10] given at the symposium ”Researches on isometries as preserver problems and related topics” at Kyoto RIMS. That is, the role of Dirac masses by describing the isometry group of various metric spaces of probability measures. This article is of survey character, and it does not contain any essentially new results.From an isometric point of view, in some cases, metric spaces of measures are similar to C(K)-type function spaces. Similarity means here that their isometries are driven by some nice transformations of the underlying space. Of course, it depends on the particular choice of the metric how nice these transformations should be. Sometimes, as we will see, being a homeomorphism is enough to generate an isometry. But sometimes we need more: the transformation must preserve the underlying distance as well. Statements claiming that isometries in questions are necessarily induced by homeomorphisms are called Banach-Stone-type results, while results asserting that the underlying transformation is necessarily an isometry are termed as isometric rigidity results.As Dirac masses can be considered as building bricks of the set of all Borel measures, a natural question arises:Is it enough to understand how an isometry acts on the set of Dirac masses? Does this action extend uniquely to all measures?In what follows, we will thoroughly investigate this question.}, author = {Geher, Gyorgy Pal and Titkos, Tamas and Virosztek, Daniel}, booktitle = {Kyoto RIMS Kôkyûroku}, location = {Kyoto, Japan}, pages = {34--41}, publisher = {Research Institute for Mathematical Sciences, Kyoto University}, title = {{Dirac masses and isometric rigidity}}, volume = {2125}, year = {2019}, } @book{7171, abstract = {Wissen Sie, was sich hinter künstlicher Intelligenz und maschinellem Lernen verbirgt? Dieses Sachbuch erklärt Ihnen leicht verständlich und ohne komplizierte Formeln die grundlegenden Methoden und Vorgehensweisen des maschinellen Lernens. Mathematisches Vorwissen ist dafür nicht nötig. Kurzweilig und informativ illustriert Lisa, die Protagonistin des Buches, diese anhand von Alltagssituationen. Ein Buch für alle, die in Diskussionen über Chancen und Risiken der aktuellen Entwicklung der künstlichen Intelligenz und des maschinellen Lernens mit Faktenwissen punkten möchten. Auch für Schülerinnen und Schüler geeignet!}, editor = {Kersting, Kristian and Lampert, Christoph and Rothkopf, Constantin}, isbn = {978-3-658-26762-9}, pages = {XIV, 245}, publisher = {Springer Nature}, title = {{Wie Maschinen Lernen: Künstliche Intelligenz Verständlich Erklärt}}, doi = {10.1007/978-3-658-26763-6}, year = {2019}, } @inproceedings{7401, abstract = {The genus g(G) of a graph G is the minimum g such that G has an embedding on the orientable surface M_g of genus g. A drawing of a graph on a surface is independently even if every pair of nonadjacent edges in the drawing crosses an even number of times. The Z_2-genus of a graph G, denoted by g_0(G), is the minimum g such that G has an independently even drawing on M_g. By a result of Battle, Harary, Kodama and Youngs from 1962, the graph genus is additive over 2-connected blocks. In 2013, Schaefer and Stefankovic proved that the Z_2-genus of a graph is additive over 2-connected blocks as well, and asked whether this result can be extended to so-called 2-amalgamations, as an analogue of results by Decker, Glover, Huneke, and Stahl for the genus. We give the following partial answer. If G=G_1 cup G_2, G_1 and G_2 intersect in two vertices u and v, and G-u-v has k connected components (among which we count the edge uv if present), then |g_0(G)-(g_0(G_1)+g_0(G_2))|<=k+1. For complete bipartite graphs K_{m,n}, with n >= m >= 3, we prove that g_0(K_{m,n})/g(K_{m,n})=1-O(1/n). Similar results are proved also for the Euler Z_2-genus. We express the Z_2-genus of a graph using the minimum rank of partial symmetric matrices over Z_2; a problem that might be of independent interest. }, author = {Fulek, Radoslav and Kyncl, Jan}, booktitle = {35th International Symposium on Computational Geometry (SoCG 2019)}, isbn = {978-3-95977-104-7}, issn = {1868-8969}, location = {Portland, OR, United States}, publisher = {Schloss Dagstuhl - Leibniz-Zentrum für Informatik}, title = {{Z_2-Genus of graphs and minimum rank of partial symmetric matrices}}, doi = {10.4230/LIPICS.SOCG.2019.39}, volume = {129}, year = {2019}, }