@article{439, abstract = {We count points over a finite field on wild character varieties,of Riemann surfaces for singularities with regular semisimple leading term. The new feature in our counting formulas is the appearance of characters of Yokonuma–Hecke algebras. Our result leads to the conjecture that the mixed Hodge polynomials of these character varieties agree with previously conjectured perverse Hodge polynomials of certain twisted parabolic Higgs moduli spaces, indicating the possibility of a P = W conjecture for a suitable wild Hitchin system.}, author = {Hausel, Tamas and Mereb, Martin and Wong, Michael}, journal = {Journal of the European Mathematical Society}, publisher = {European Mathematical Society}, title = {{Arithmetic and representation theory of wild character varieties}}, year = {2019}, } @inproceedings{5947, abstract = {Graph algorithms applied in many applications, including social networks, communication networks, VLSI design, graphics, and several others, require dynamic modifications - addition and removal of vertices and/or edges - in the graph. This paper presents a novel concurrent non-blocking algorithm to implement a dynamic unbounded directed graph in a shared-memory machine. The addition and removal operations of vertices and edges are lock-free. For a finite sized graph, the lookup operations are wait-free. Most significant component of the presented algorithm is the reachability query in a concurrent graph. The reachability queries in our algorithm are obstruction-free and thus impose minimal additional synchronization cost over other operations. We prove that each of the data structure operations are linearizable. We extensively evaluate a sample C/C++ implementation of the algorithm through a number of micro-benchmarks. The experimental results show that the proposed algorithm scales well with the number of threads and on an average provides 5 to 7x performance improvement over a concurrent graph implementation using coarse-grained locking.}, author = {Chatterjee, Bapi and Peri, Sathya and Sa, Muktikanta and Singhal, Nandini}, booktitle = {ACM International Conference Proceeding Series}, isbn = {978-1-4503-6094-4 }, location = {Bangalore, India}, pages = {168--177}, publisher = {ACM}, title = {{A simple and practical concurrent non-blocking unbounded graph with linearizable reachability queries}}, doi = {10.1145/3288599.3288617}, year = {2019}, } @article{6022, abstract = {The evolution of new species is made easier when traits under divergent ecological selection are also mating cues. Such ecological mating cues are now considered more common than previously thought, but we still know little about the genetic changes underlying their evolution or more generally about the genetic basis for assortative mating behaviors. Both tight physical linkage and the existence of large-effect preference loci will strengthen genetic associations between behavioral and ecological barriers, promoting the evolution of assortative mating. The warning patterns of Heliconius melpomene and H. cydno are under disruptive selection due to increased predation of nonmimetic hybrids and are used during mate recognition. We carried out a genome-wide quantitative trait locus (QTL) analysis of preference behaviors between these species and showed that divergent male preference has a simple genetic basis. We identify three QTLs that together explain a large proportion (approximately 60%) of the difference in preference behavior observed between the parental species. One of these QTLs is just 1.2 (0-4.8) centiMorgans (cM) from the major color pattern gene optix, and, individually, all three have a large effect on the preference phenotype. Genomic divergence between H. cydno and H. melpomene is high but broadly heterogenous, and admixture is reduced at the preference-optix color pattern locus but not the other preference QTLs. The simple genetic architecture we reveal will facilitate the evolution and maintenance of new species despite ongoing gene flow by coupling behavioral and ecological aspects of reproductive isolation.}, author = {Merrill, Richard M. and Rastas, Pasi and Martin, Simon H. and Melo Hurtado, Maria C and Barker, Sarah and Davey, John and Mcmillan, W. Owen and Jiggins, Chris D.}, journal = {PLoS Biology}, number = {2}, publisher = {Public Library of Science}, title = {{Genetic dissection of assortative mating behavior}}, doi = {10.1371/journal.pbio.2005902}, volume = {17}, year = {2019}, } @article{6046, abstract = {Sudden stress often triggers diverse, temporally structured gene expression responses in microbes, but it is largely unknown how variable in time such responses are and if genes respond in the same temporal order in every single cell. Here, we quantified timing variability of individual promoters responding to sublethal antibiotic stress using fluorescent reporters, microfluidics, and time‐lapse microscopy. We identified lower and upper bounds that put definite constraints on timing variability, which varies strongly among promoters and conditions. Timing variability can be interpreted using results from statistical kinetics, which enable us to estimate the number of rate‐limiting molecular steps underlying different responses. We found that just a few critical steps control some responses while others rely on dozens of steps. To probe connections between different stress responses, we then tracked the temporal order and response time correlations of promoter pairs in individual cells. Our results support that, when bacteria are exposed to the antibiotic nitrofurantoin, the ensuing oxidative stress and SOS responses are part of the same causal chain of molecular events. In contrast, under trimethoprim, the acid stress response and the SOS response are part of different chains of events running in parallel. Our approach reveals fundamental constraints on gene expression timing and provides new insights into the molecular events that underlie the timing of stress responses.}, author = {Mitosch, Karin and Rieckh, Georg and Bollenbach, Mark Tobias}, journal = {Molecular systems biology}, number = {2}, publisher = {Embo Press}, title = {{Temporal order and precision of complex stress responses in individual bacteria}}, doi = {10.15252/msb.20188470}, volume = {15}, year = {2019}, } @article{6053, abstract = {Recent technical developments in the fields of quantum electromechanics and optomechanics have spawned nanoscale mechanical transducers with the sensitivity to measure mechanical displacements at the femtometre scale and the ability to convert electromagnetic signals at the single photon level. A key challenge in this field is obtaining strong coupling between motion and electromagnetic fields without adding additional decoherence. Here we present an electromechanical transducer that integrates a high-frequency (0.42 GHz) hypersonic phononic crystal with a superconducting microwave circuit. The use of a phononic bandgap crystal enables quantum-level transduction of hypersonic mechanical motion and concurrently eliminates decoherence caused by acoustic radiation. Devices with hypersonic mechanical frequencies provide a natural pathway for integration with Josephson junction quantum circuits, a leading quantum computing technology, and nanophotonic systems capable of optical networking and distributing quantum information.}, author = {Kalaee, Mahmoud and Mirhosseini, Mohammad and Dieterle, Paul B. and Peruzzo, Matilda and Fink, Johannes M and Painter, Oskar}, journal = {Nature Nanotechnology}, publisher = {Springer Nature}, title = {{Quantum electromechanics of a hypersonic crystal}}, doi = {10.1038/s41565-019-0377-2}, year = {2019}, } @article{6089, abstract = {Pleiotropy is the well-established idea that a single mutation affects multiple phenotypes. If a mutation has opposite effects on fitness when expressed in different contexts, then genetic conflict arises. Pleiotropic conflict is expected to reduce the efficacy of selection by limiting the fixation of beneficial mutations through adaptation, and the removal of deleterious mutations through purifying selection. Although this has been widely discussed, in particular in the context of a putative “gender load,” it has yet to be systematically quantified. In this work, we empirically estimate to which extent different pleiotropic regimes impede the efficacy of selection in Drosophila melanogaster. We use whole-genome polymorphism data from a single African population and divergence data from D. simulans to estimate the fraction of adaptive fixations (α), the rate of adaptation (ωA), and the direction of selection (DoS). After controlling for confounding covariates, we find that the different pleiotropic regimes have a relatively small, but significant, effect on selection efficacy. Specifically, our results suggest that pleiotropic sexual antagonism may restrict the efficacy of selection, but that this conflict can be resolved by limiting the expression of genes to the sex where they are beneficial. Intermediate levels of pleiotropy across tissues and life stages can also lead to maladaptation in D. melanogaster, due to inefficient purifying selection combined with low frequency of mutations that confer a selective advantage. Thus, our study highlights the need to consider the efficacy of selection in the context of antagonistic pleiotropy, and of genetic conflict in general.}, author = {Fraisse, Christelle and Puixeu Sala, Gemma and Vicoso, Beatriz}, journal = {Molecular biology and evolution}, number = {3}, pages = {500--515}, publisher = {Oxford Academic}, title = {{Pleiotropy modulates the efficacy of selection in drosophila melanogaster}}, doi = {10.1093/molbev/msy246}, volume = {36}, year = {2019}, } @article{6091, abstract = {Cortical networks are characterized by sparse connectivity, with synapses found at only a subset of axo-dendritic contacts. Yet within these networks, neurons can exhibit high connection probabilities, suggesting that cell-intrinsic factors, not proximity, determine connectivity. Here, we identify ephrin-B3 (eB3) as a factor that determines synapse density by mediating a cell-cell competition that requires ephrin-B-EphB signaling. In a microisland culture system designed to isolate cell-cell competition, we find that eB3 determines winning and losing neurons in a contest for synapses. In a Mosaic Analysis with Double Markers (MADM) genetic mouse model system in vivo the relative levels of eB3 control spine density in layer 5 and 6 neurons. MADM cortical neurons in vitro reveal that eB3 controls synapse density independently of action potential-driven activity. Our findings illustrate a new class of competitive mechanism mediated by trans-synaptic organizing proteins which control the number of synapses neurons receive relative to neighboring neurons.}, author = {Henderson, Nathan T. and Le Marchand, Sylvain J. and Hruska, Martin and Hippenmeyer, Simon and Luo, Liqun and Dalva, Matthew B.}, journal = {eLife}, publisher = {eLife Sciences Publications}, title = {{Ephrin-B3 controls excitatory synapse density through cell-cell competition for EphBs}}, doi = {10.7554/eLife.41563}, volume = {8}, year = {2019}, } @unpublished{6313, abstract = {We prove three principal results. First we exhibit a drawing of $K_{10}$ in the plane for which there do not exist extensions of the edges to simple closed curves with any two curves intersecting at most twice. Second, we exhibit a drawing of $K_9$ that has an extension of its edges to simple closed curves such that any two curves intersect in at most two points, but no extension to simple closed curves has every two curves intersecting in exactly two points. Third, we show that every h-convex drawing (introduced by Arroyo et al, submitted) has extensions of its edges to simple closed curves such that any two curves intersect in exactly two points. Using this result, we show that} a set of three axioms of simple closed curve extensions characterizes h-convexity.}, author = {Arroyo Guevara, Alan M and Richter, Bruce and Sunohara, Matthew}, pages = {35}, title = {{Extending drawings of complete graphs into arrangements of pseudocircles}}, year = {2019}, } @article{6351, abstract = {A process of restorative patterning in plant roots correctly replaces eliminated cells to heal local injuries despite the absence of cell migration, which underpins wound healing in animals. Patterning in plants relies on oriented cell divisions and acquisition of specific cell identities. Plants regularly endure wounds caused by abiotic or biotic environmental stimuli and have developed extraordinary abilities to restore their tissues after injuries. Here, we provide insight into a mechanism of restorative patterning that repairs tissues after wounding. Laser-assisted elimination of different cells in Arabidopsis root combined with live-imaging tracking during vertical growth allowed analysis of the regeneration processes in vivo. Specifically, the cells adjacent to the inner side of the injury re-activated their stem cell transcriptional programs. They accelerated their progression through cell cycle, coordinately changed the cell division orientation, and ultimately acquired de novo the correct cell fates to replace missing cells. These observations highlight existence of unknown intercellular positional signaling and demonstrate the capability of specified cells to re-acquire stem cell programs as a crucial part of the plant-specific mechanism of wound healing.}, author = {Marhavá, Petra and Hörmayer, Lukas and Yoshida, Saiko and Marhavy, Peter and Benková, Eva and Friml, Jiří}, issn = {10974172}, journal = {Cell}, number = {4}, pages = {957--969.e13}, publisher = {Elsevier}, title = {{Re-activation of stem cell pathways for pattern restoration in plant wound healing}}, doi = {10.1016/j.cell.2019.04.015}, volume = {177}, year = {2019}, } @article{6262, abstract = {Gravitropism is an adaptive response that orients plant growth parallel to the gravity vector. Asymmetric distribution of the phytohormone auxin is a necessary prerequisite to the tropic bending both in roots and shoots. During hypocotyl gravitropic response, the PIN3 auxin transporter polarizes within gravity-sensing cells to redirect intercellular auxin fluxes. First gravity-induced PIN3 polarization to the bottom cell mem- branes leads to the auxin accumulation at the lower side of the organ, initiating bending and, later, auxin feedback-mediated repolarization restores symmetric auxin distribution to terminate bending. Here, we per- formed a forward genetic screen to identify regulators of both PIN3 polarization events during gravitropic response. We searched for mutants with defective PIN3 polarizations based on easy-to-score morphological outputs of decreased or increased gravity-induced hypocotyl bending. We identified the number of hypocotyl reduced bending (hrb) and hypocotyl hyperbending (hhb) mutants, revealing that reduced bending corre- lated typically with defective gravity-induced PIN3 relocation whereas all analyzed hhb mutants showed defects in the second, auxin-mediated PIN3 relocation. Next-generation sequencing-aided mutation map- ping identified several candidate genes, including SCARECROW and ACTIN2, revealing roles of endodermis specification and actin cytoskeleton in the respective gravity- and auxin-induced PIN polarization events. The hypocotyl gravitropism screen thus promises to provide novel insights into mechanisms underlying cell polarity and plant adaptive development.}, author = {Rakusová, Hana and Han, Huibin and Valošek, Petr and Friml, Jiří}, issn = {0960-7412}, journal = {The Plant Journal}, publisher = {Wiley}, title = {{Genetic screen for factors mediating PIN polarization in gravistimulated Arabidopsis thaliana hypocotyls}}, doi = {10.1111/tpj.14301}, year = {2019}, } @article{6488, abstract = {We prove a central limit theorem for the difference of linear eigenvalue statistics of a sample covariance matrix W˜ and its minor W. We find that the fluctuation of this difference is much smaller than those of the individual linear statistics, as a consequence of the strong correlation between the eigenvalues of W˜ and W. Our result identifies the fluctuation of the spatial derivative of the approximate Gaussian field in the recent paper by Dumitru and Paquette. Unlike in a similar result for Wigner matrices, for sample covariance matrices, the fluctuation may entirely vanish.}, author = {Cipolloni, Giorgio and Erdös, László}, issn = {20103271}, journal = {Random Matrices: Theory and Application}, publisher = {World Scientific Publishing}, title = {{Fluctuations for differences of linear eigenvalue statistics for sample covariance matrices}}, doi = {10.1142/S2010326320500069}, year = {2019}, } @article{6419, abstract = {Characterizing the fitness landscape, a representation of fitness for a large set of genotypes, is key to understanding how genetic information is interpreted to create functional organisms. Here we determined the evolutionarily-relevant segment of the fitness landscape of His3, a gene coding for an enzyme in the histidine synthesis pathway, focusing on combinations of amino acid states found at orthologous sites of extant species. Just 15% of amino acids found in yeast His3 orthologues were always neutral while the impact on fitness of the remaining 85% depended on the genetic background. Furthermore, at 67% of sites, amino acid replacements were under sign epistasis, having both strongly positive and negative effect in different genetic backgrounds. 46% of sites were under reciprocal sign epistasis. The fitness impact of amino acid replacements was influenced by only a few genetic backgrounds but involved interaction of multiple sites, shaping a rugged fitness landscape in which many of the shortest paths between highly fit genotypes are inaccessible.}, author = {Pokusaeva, Victoria and Usmanova, Dinara R. and Putintseva, Ekaterina V. and Espinar, Lorena and Sarkisyan, Karen and Mishin, Alexander S. and Bogatyreva, Natalya S. and Ivankov, Dmitry and Akopyan, Arseniy and Avvakumov, Sergey and Povolotskaya, Inna S. and Filion, Guillaume J. and Carey, Lucas B. and Kondrashov, Fyodor}, issn = {15537404}, journal = {PLoS Genetics}, number = {4}, publisher = {Public Library of Science}, title = {{An experimental assay of the interactions of amino acids from orthologous sequences shaping a complex fitness landscape}}, doi = {10.1371/journal.pgen.1008079}, volume = {15}, year = {2019}, } @article{6596, abstract = {It is well known that many problems in image recovery, signal processing, and machine learning can be modeled as finding zeros of the sum of maximal monotone and Lipschitz continuous monotone operators. Many papers have studied forward-backward splitting methods for finding zeros of the sum of two monotone operators in Hilbert spaces. Most of the proposed splitting methods in the literature have been proposed for the sum of maximal monotone and inverse-strongly monotone operators in Hilbert spaces. In this paper, we consider splitting methods for finding zeros of the sum of maximal monotone operators and Lipschitz continuous monotone operators in Banach spaces. We obtain weak and strong convergence results for the zeros of the sum of maximal monotone and Lipschitz continuous monotone operators in Banach spaces. Many already studied problems in the literature can be considered as special cases of this paper.}, author = {Shehu, Yekini}, issn = {1420-9012}, journal = {Results in Mathematics}, number = {4}, publisher = {Springer}, title = {{Convergence results of forward-backward algorithms for sum of monotone operators in Banach spaces}}, doi = {10.1007/s00025-019-1061-4}, volume = {74}, year = {2019}, } @article{6609, abstract = {Mechanical systems facilitate the development of a hybrid quantum technology comprising electrical, optical, atomic and acoustic degrees of freedom1, and entanglement is essential to realize quantum-enabled devices. Continuous-variable entangled fields—known as Einstein–Podolsky–Rosen (EPR) states—are spatially separated two-mode squeezed states that can be used for quantum teleportation and quantum communication2. In the optical domain, EPR states are typically generated using nondegenerate optical amplifiers3, and at microwave frequencies Josephson circuits can serve as a nonlinear medium4,5,6. An outstanding goal is to deterministically generate and distribute entangled states with a mechanical oscillator, which requires a carefully arranged balance between excitation, cooling and dissipation in an ultralow noise environment. Here we observe stationary emission of path-entangled microwave radiation from a parametrically driven 30-micrometre-long silicon nanostring oscillator, squeezing the joint field operators of two thermal modes by 3.40 decibels below the vacuum level. The motion of this micromechanical system correlates up to 50 photons per second per hertz, giving rise to a quantum discord that is robust with respect to microwave noise7. Such generalized quantum correlations of separable states are important for quantum-enhanced detection8 and provide direct evidence of the non-classical nature of the mechanical oscillator without directly measuring its state9. This noninvasive measurement scheme allows to infer information about otherwise inaccessible objects, with potential implications for sensing, open-system dynamics and fundamental tests of quantum gravity. In the future, similar on-chip devices could be used to entangle subsystems on very different energy scales, such as microwave and optical photons.}, author = {Barzanjeh, Shabir and Redchenko, Elena and Peruzzo, Matilda and Wulf, Matthias and Lewis, Dylan and Arnold, Georg M and Fink, Johannes M}, journal = {Nature}, pages = {480--483}, publisher = {Nature Publishing Group}, title = {{Stationary entangled radiation from micromechanical motion}}, doi = {10.1038/s41586-019-1320-2}, volume = {570}, year = {2019}, } @article{6717, abstract = {With the recent publication by Silpe and Bassler (2019), considering phage detection of a bacterial quorum-sensing (QS) autoinducer, we now have as many as five examples of phage-associated intercellular communication (Table 1). Each potentially involves ecological inferences by phages as to concentrations of surrounding phage-infected or uninfected bacteria. While the utility of phage detection of bacterial QS molecules may at first glance appear to be straightforward, we suggest in this commentary that the underlying ecological explanation is unlikely to be simple.}, author = {Igler, Claudia and Abedon, Stephen T.}, journal = {Frontiers in Microbiology}, publisher = {Frontiers}, title = {{Commentary: A host-produced quorum-sensing autoinducer controls a phage lysis-lysogeny decision}}, doi = {10.3389/fmicb.2019.01171}, volume = {10}, year = {2019}, } @article{6611, abstract = {Cell polarity is crucial for the coordinated development of all multicellular organisms. In plants, this is exemplified by the PIN-FORMED (PIN) efflux carriers of the phytohormone auxin: The polar subcellular localization of the PINs is instructive to the directional intercellular auxin transport, and thus to a plethora of auxin-regulated growth and developmental processes. Despite its importance, the regulation of PIN polar subcellular localization remains poorly understood. Here, we have employed advanced live-cell imaging techniques to study the roles of microtubules and actin microfilaments in the establishment of apical polar localization of PIN2 in the epidermis of the Arabidopsis root meristem. We report that apical PIN2 polarity requires neither intact actin microfilaments nor microtubules, suggesting that the primary spatial cue for polar PIN distribution is likely independent of cytoskeleton-guided endomembrane trafficking.}, author = {Glanc, Matous and Fendrych, Matyas and Friml, Jiří}, journal = {Biomolecules}, number = {6}, publisher = {MDPI}, title = {{PIN2 polarity establishment in arabidopsis in the absence of an intact cytoskeleton}}, doi = {10.3390/biom9060222}, volume = {9}, year = {2019}, } @inproceedings{6642, abstract = {We present a thermodynamically based approach to the design of models for viscoelastic fluids with stress diffusion effect. In particular, we show how to add a stress diffusion term to some standard viscoelastic rate-type models (Giesekus, FENE-P, Johnson–Segalman, Phan-Thien–Tanner and Bautista–Manero–Puig) so that the resulting models with the added stress diffusion term are thermodynamically consistent in the sense that they obey the first and the second law of thermodynamics. We point out the potential applications of the provided thermodynamical background in the study of flows of fluids described by the proposed models.}, author = {Dostalík, Mark and Průša, Vít and Skrivan, Tomas}, booktitle = {AIP Conference Proceedings}, location = {Zlin, Czech Republic}, publisher = {AIP}, title = {{On diffusive variants of some classical viscoelastic rate-type models}}, doi = {10.1063/1.5109493}, volume = {2107}, year = {2019}, } @inproceedings{6647, abstract = {The Tverberg theorem is one of the cornerstones of discrete geometry. It states that, given a set X of at least (d+1)(r-1)+1 points in R^d, one can find a partition X=X_1 cup ... cup X_r of X, such that the convex hulls of the X_i, i=1,...,r, all share a common point. In this paper, we prove a strengthening of this theorem that guarantees a partition which, in addition to the above, has the property that the boundaries of full-dimensional convex hulls have pairwise nonempty intersections. Possible generalizations and algorithmic aspects are also discussed. As a concrete application, we show that any n points in the plane in general position span floor[n/3] vertex-disjoint triangles that are pairwise crossing, meaning that their boundaries have pairwise nonempty intersections; this number is clearly best possible. A previous result of Alvarez-Rebollar et al. guarantees floor[n/6] pairwise crossing triangles. Our result generalizes to a result about simplices in R^d,d >=2.}, author = {Fulek, Radoslav and Gärtner, Bernd and Kupavskii, Andrey and Valtr, Pavel and Wagner, Uli}, booktitle = {35th International Symposium on Computational Geometry}, isbn = {9783959771047}, issn = {1868-8969}, location = {Portland, OR, United States}, pages = {38:1--38:13}, publisher = {Schloss Dagstuhl - Leibniz-Zentrum für Informatik}, title = {{The crossing Tverberg theorem}}, doi = {10.4230/LIPICS.SOCG.2019.38}, volume = {129}, year = {2019}, } @article{73, abstract = {We consider the space of probability measures on a discrete set X, endowed with a dynamical optimal transport metric. Given two probability measures supported in a subset Y⊆X, it is natural to ask whether they can be connected by a constant speed geodesic with support in Y at all times. Our main result answers this question affirmatively, under a suitable geometric condition on Y introduced in this paper. The proof relies on an extension result for subsolutions to discrete Hamilton-Jacobi equations, which is of independent interest.}, author = {Erbar, Matthias and Maas, Jan and Wirth, Melchior}, issn = {09442669}, journal = {Calculus of Variations and Partial Differential Equations}, number = {1}, publisher = {Springer}, title = {{On the geometry of geodesics in discrete optimal transport}}, doi = {10.1007/s00526-018-1456-1}, volume = {58}, year = {2019}, } @article{6755, abstract = {Differentiated sex chromosomes are accompanied by a difference in gene dose between X/Z-specific and autosomal genes. At the transcriptomic level, these sex-linked genes can lead to expression imbalance, or gene dosage can be compensated by epigenetic mechanisms and results into expression level equalization. Schistosoma mansoni has been previously described as a ZW species (i.e., female heterogamety, in opposition to XY male heterogametic species) with a partial dosage compensation, but underlying mechanisms are still unexplored. Here, we combine transcriptomic (RNA-Seq) and epigenetic data (ChIP-Seq against H3K4me3, H3K27me3,andH4K20me1histonemarks) in free larval cercariae and intravertebrate parasitic stages. For the first time, we describe differences in dosage compensation status in ZW females, depending on the parasitic status: free cercariae display global dosage compensation, whereas intravertebrate stages show a partial dosage compensation. We also highlight regional differences of gene expression along the Z chromosome in cercariae, but not in the intravertebrate stages. Finally, we feature a consistent permissive chromatin landscape of the Z chromosome in both sexes and stages. We argue that dosage compensation in schistosomes is characterized by chromatin remodeling mechanisms in the Z-specific region.}, author = {Picard, Marion A L and Vicoso, Beatriz and Roquis, David and Bulla, Ingo and Augusto, Ronaldo C. and Arancibia, Nathalie and Grunau, Christoph and Boissier, Jérôme and Cosseau, Céline}, issn = {17596653}, journal = {Genome biology and evolution}, number = {7}, pages = {1909--1922}, publisher = {Oxford Academic Press}, title = {{Dosage compensation throughout the Schistosoma mansoni lifecycle: Specific chromatin landscape of the Z chromosome}}, doi = {10.1093/gbe/evz133}, volume = {11}, year = {2019}, } @article{6762, abstract = {We present and study novel optimal control problems motivated by the search for photovoltaic materials with high power-conversion efficiency. The material must perform the first step: convert light (photons) into electronic excitations. We formulate various desirable properties of the excitations as mathematical control goals at the Kohn-Sham-DFT level of theory, with the control being given by the nuclear charge distribution. We prove that nuclear distributions exist which give rise to optimal HOMO-LUMO excitations, and present illustrative numerical simulations for 1D finite nanocrystals. We observe pronounced goal-dependent features such as large electron-hole separation, and a hierarchy of length scales: internal HOMO and LUMO wavelengths < atomic spacings < (irregular) fluctuations of the doping profiles < system size.}, author = {Friesecke, Gero and Kniely, Michael}, issn = {15403467}, journal = {Multiscale Modeling and Simulation}, number = {3}, pages = {926--947}, publisher = {SIAM}, title = {{New optimal control problems in density functional theory motivated by photovoltaics}}, doi = {10.1137/18M1207272}, volume = {17}, year = {2019}, } @article{6786, abstract = {Dipolar coupling plays a fundamental role in the interaction between electrically or magnetically polarized species such as magnetic atoms and dipolar molecules in a gas or dipolar excitons in the solid state. Unlike Coulomb or contactlike interactions found in many atomic, molecular, and condensed-matter systems, this interaction is long-ranged and highly anisotropic, as it changes from repulsive to attractive depending on the relative positions and orientation of the dipoles. Because of this unique property, many exotic, symmetry-breaking collective states have been recently predicted for cold dipolar gases, but only a few have been experimentally detected and only in dilute atomic dipolar Bose-Einstein condensates. Here, we report on the first observation of attractive dipolar coupling between excitonic dipoles using a new design of stacked semiconductor bilayers. We show that the presence of a dipolar exciton fluid in one bilayer modifies the spatial distribution and increases the binding energy of excitonic dipoles in a vertically remote layer. The binding energy changes are explained using a many-body polaron model describing the deformation of the exciton cloud due to its interaction with a remote dipolar exciton. The surprising nonmonotonic dependence on the cloud density indicates the important role of dipolar correlations, which is unique to dense, strongly interacting dipolar solid-state systems. Our concept provides a route for the realization of dipolar lattices with strong anisotropic interactions in semiconductor systems, which open the way for the observation of theoretically predicted new and exotic collective phases, as well as for engineering and sensing their collective excitations.}, author = {Hubert, Colin and Baruchi, Yifat and Mazuz-Harpaz, Yotam and Cohen, Kobi and Biermann, Klaus and Lemeshko, Mikhail and West, Ken and Pfeiffer, Loren and Rapaport, Ronen and Santos, Paulo}, issn = {2160-3308}, journal = {Physical Review X}, number = {2}, publisher = {APS}, title = {{Attractive dipolar coupling between stacked exciton fluids}}, doi = {10.1103/PhysRevX.9.021026}, volume = {9}, year = {2019}, } @article{6779, abstract = {Recent studies suggest that unstable recurrent solutions of the Navier-Stokes equation provide new insights into dynamics of turbulent flows. In this study, we compute an extensive network of dynamical connections between such solutions in a weakly turbulent quasi-two-dimensional Kolmogorov flow that lies in the inversion symmetric subspace. In particular, we find numerous isolated heteroclinic connections between different types of solutions—equilibria, periodic, and quasiperiodic orbits—as well as continua of connections forming higher-dimensional connecting manifolds. We also compute a homoclinic connection of a periodic orbit and provide strong evidence that the associated homoclinic tangle forms the chaotic repeller that underpins transient turbulence in the symmetric subspace.}, author = {Suri, Balachandra and Pallantla, Ravi Kumar and Schatz, Michael F. and Grigoriev, Roman O.}, issn = {2470-0053}, journal = {Physical Review E}, number = {1}, publisher = {APS}, title = {{Heteroclinic and homoclinic connections in a Kolmogorov-like flow}}, doi = {10.1103/physreve.100.013112}, volume = {100}, year = {2019}, } @article{6793, abstract = {The Regge symmetry is a set of remarkable relations between two tetrahedra whose edge lengths are related in a simple fashion. It was first discovered as a consequence of an asymptotic formula in mathematical physics. Here, we give a simple geometric proof of Regge symmetries in Euclidean, spherical, and hyperbolic geometry.}, author = {Akopyan, Arseniy and Izmestiev, Ivan}, issn = {14692120}, journal = {Bulletin of the London Mathematical Society}, publisher = {London Mathematical Society}, title = {{The Regge symmetry, confocal conics, and the Schläfli formula}}, doi = {10.1112/blms.12276}, 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}, } @article{6844, abstract = {Studying the progression of the proliferative and differentiative patterns of neural stem cells at the individual cell level is crucial to the understanding of cortex development and how the disruption of such patterns can lead to malformations and neurodevelopmental diseases. However, our understanding of the precise lineage progression programme at single-cell resolution is still incomplete due to the technical variations in lineage- tracing approaches. One of the key challenges involves developing a robust theoretical framework in which we can integrate experimental observations and introduce correction factors to obtain a reliable and representative description of the temporal modulation of proliferation and differentiation. In order to obtain more conclusive insights, we carry out virtual clonal analysis using mathematical modelling and compare our results against experimental data. Using a dataset obtained with Mosaic Analysis with Double Markers, we illustrate how the theoretical description can be exploited to interpret and reconcile the disparity between virtual and experimental results.}, author = {Picco, Noemi and Hippenmeyer, Simon and Rodarte, Julio and Streicher, Carmen and Molnár, Zoltán and Maini, Philip K. and Woolley, Thomas E.}, issn = {1469-7580}, journal = {Journal of Anatomy}, number = {3}, pages = {686--696}, publisher = {Wiley}, title = {{A mathematical insight into cell labelling experiments for clonal analysis}}, doi = {10.1111/joa.13001}, volume = {235}, 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}, } @article{6868, abstract = {Hyperpolarization-activated cyclic-nucleotide-gated (HCN) channels control electrical rhythmicity and excitability in the heart and brain, but the function of HCN channels at the subcellular level in axons remains poorly understood. Here, we show that the action potential conduction velocity in both myelinated and unmyelinated central axons can be bidirectionally modulated by a HCN channel blocker, cyclic adenosine monophosphate (cAMP), and neuromodulators. Recordings from mouse cerebellar mossy fiber boutons show that HCN channels ensure reliable high-frequency firing and are strongly modulated by cAMP (EC50 40 mM; estimated endogenous cAMP concentration 13 mM). In addition, immunogold-electron microscopy revealed HCN2 as the dominating subunit in cerebellar mossy fibers. Computational modeling indicated that HCN2 channels control conduction velocity primarily by altering the resting membrane potential and are associated with significant metabolic costs. These results suggest that the cAMP-HCN pathway provides neuromodulators with an opportunity to finely tune energy consumption and temporal delays across axons in the brain.}, author = {Byczkowicz, Niklas and Eshra, Abdelmoneim and Montanaro-Punzengruber, Jacqueline-Claire and Trevisiol, Andrea and Hirrlinger, Johannes and Kole, Maarten Hp and Shigemoto, Ryuichi and Hallermann, Stefan}, issn = {2050084X}, journal = {eLife}, publisher = {eLife Sciences Publications}, title = {{HCN channel-mediated neuromodulation can control action potential velocity and fidelity in central axons}}, doi = {10.7554/eLife.42766}, volume = {8}, year = {2019}, } @article{6680, abstract = {This paper analyzes how partial selfing in a large source population influences its ability to colonize a new habitat via the introduction of a few founder individuals. Founders experience inbreeding depression due to partially recessive deleterious alleles as well as maladaptation to the new environment due to selection on a large number of additive loci. I first introduce a simplified version of the Inbreeding History Model (Kelly, 2007) in order to characterize mutation‐selection balance in a large, partially selfing source population under selection involving multiple non‐identical loci. I then use individual‐based simulations to study the eco‐evolutionary dynamics of founders establishing in the new habitat under a model of hard selection. The study explores how selfing rate shapes establishment probabilities of founders via effects on both inbreeding depression and adaptability to the new environment, and also distinguishes the effects of selfing on the initial fitness of founders from its effects on the long‐term adaptive response of the populations they found. A high rate of (but not complete) selfing is found to aid establishment over a wide range of parameters, even in the absence of mate limitation. The sensitivity of the results to assumptions about the nature of polygenic selection are discussed.}, author = {Sachdeva, Himani}, issn = {1558-5646}, journal = {Evolution}, number = {9}, pages = {1729--1745}, publisher = {Wiley}, title = {{Effect of partial selfing and polygenic selection on establishment in a new habitat}}, doi = {10.1111/evo.13812}, volume = {73}, year = {2019}, } @article{151, abstract = {We construct planar bi-Sobolev mappings whose local volume distortion is bounded from below by a given function f∈Lp with p>1. More precisely, for any 1<q<(p+1)/2 we construct W1,q-bi-Sobolev maps with identity boundary conditions; for f∈L∞, we provide bi-Lipschitz maps. The basic building block of our construction are bi-Lipschitz maps which stretch a given compact subset of the unit square by a given factor while preserving the boundary. The construction of these stretching maps relies on a slight strengthening of the celebrated covering result of Alberti, Csörnyei, and Preiss for measurable planar sets in the case of compact sets. We apply our result to a model functional in nonlinear elasticity, the integrand of which features fast blowup as the Jacobian determinant of the deformation becomes small. For such functionals, the derivation of the equilibrium equations for minimizers requires an additional regularization of test functions, which our maps provide.}, author = {Fischer, Julian L and Kneuss, Olivier}, journal = {Journal of Differential Equations}, number = {1}, pages = {257 -- 311}, publisher = {Academic Press}, title = {{Bi-Sobolev solutions to the prescribed Jacobian inequality in the plane with L p data and applications to nonlinear elasticity}}, doi = {10.1016/j.jde.2018.07.045}, volume = {266}, year = {2019}, } @article{175, abstract = {An upper bound sieve for rational points on suitable varieties isdeveloped, together with applications tocounting rational points in thin sets,to local solubility in families, and to the notion of “friable” rational pointswith respect to divisors. In the special case of quadrics, sharper estimates areobtained by developing a version of the Selberg sieve for rational points.}, author = {Browning, Timothy D and Loughran, Daniel}, issn = {10886850}, journal = {Transactions of the American Mathematical Society}, number = {8}, pages = {5757--5785}, publisher = {American Mathematical Society}, title = {{Sieving rational points on varieties}}, volume = {371}, year = {2019}, } @article{6023, abstract = {Multicellular development requires coordinated cell polarization relative to body axes, and translation to oriented cell division 1–3 . In plants, it is unknown how cell polarities are connected to organismal axes and translated to division. Here, we identify Arabidopsis SOSEKI proteins that integrate apical–basal and radial organismal axes to localize to polar cell edges. Localization does not depend on tissue context, requires cell wall integrity and is defined by a transferrable, protein-specific motif. A Domain of Unknown Function in SOSEKI proteins resembles the DIX oligomerization domain in the animal Dishevelled polarity regulator. The DIX-like domain self-interacts and is required for edge localization and for influencing division orientation, together with a second domain that defines the polar membrane domain. Our work shows that SOSEKI proteins locally interpret global polarity cues and can influence cell division orientation. Furthermore, this work reveals that, despite fundamental differences, cell polarity mechanisms in plants and animals converge on a similar protein domain.}, author = {Yoshida, Saiko and Van Der Schuren, Alja and Van Dop, Maritza and Van Galen, Luc and Saiga, Shunsuke and Adibi, Milad and Möller, Barbara and Ten Hove, Colette A. and Marhavy, Peter and Smith, Richard and Friml, Jiří and Weijers, Dolf}, journal = {Nature Plants}, number = {2}, pages = {160--166}, publisher = {Springer Nature}, title = {{A SOSEKI-based coordinate system interprets global polarity cues in arabidopsis}}, doi = {10.1038/s41477-019-0363-6}, volume = {5}, year = {2019}, } @article{6028, abstract = {We give a construction allowing us to build local renormalized solutions to general quasilinear stochastic PDEs within the theory of regularity structures, thus greatly generalizing the recent results of [1, 5, 11]. Loosely speaking, our construction covers quasilinear variants of all classes of equations for which the general construction of [3, 4, 7] applies, including in particular one‐dimensional systems with KPZ‐type nonlinearities driven by space‐time white noise. In a less singular and more specific case, we furthermore show that the counterterms introduced by the renormalization procedure are given by local functionals of the solution. The main feature of our construction is that it allows exploitation of a number of existing results developed for the semilinear case, so that the number of additional arguments it requires is relatively small.}, author = {Gerencser, Mate and Hairer, Martin}, journal = {Communications on Pure and Applied Mathematics}, publisher = {Wiley}, title = {{A solution theory for quasilinear singular SPDEs}}, doi = {10.1002/cpa.21816}, year = {2019}, } @inproceedings{6035, abstract = {We present JuliaReach, a toolbox for set-based reachability analysis of dynamical systems. JuliaReach consists of two main packages: Reachability, containing implementations of reachability algorithms for continuous and hybrid systems, and LazySets, a standalone library that implements state-of-the-art algorithms for calculus with convex sets. The library offers both concrete and lazy set representations, where the latter stands for the ability to delay set computations until they are needed. The choice of the programming language Julia and the accompanying documentation of our toolbox allow researchers to easily translate set-based algorithms from mathematics to software in a platform-independent way, while achieving runtime performance that is comparable to statically compiled languages. Combining lazy operations in high dimensions and explicit computations in low dimensions, JuliaReach can be applied to solve complex, large-scale problems.}, author = {Bogomolov, Sergiy and Forets, Marcelo and Frehse, Goran and Potomkin, Kostiantyn and Schilling, Christian}, booktitle = {Proceedings of the 22nd International Conference on Hybrid Systems: Computation and Control}, isbn = {9781450362825}, keyword = {reachability analysis, hybrid systems, lazy computation}, location = {Montreal, QC, Canada}, pages = {39--44}, publisher = {ACM}, title = {{JuliaReach: A toolbox for set-based reachability}}, doi = {10.1145/3302504.3311804}, volume = {22}, year = {2019}, } @inproceedings{6042, abstract = {Static program analyzers are increasingly effective in checking correctness properties of programs and reporting any errors found, often in the form of error traces. However, developers still spend a significant amount of time on debugging. This involves processing long error traces in an effort to localize a bug to a relatively small part of the program and to identify its cause. In this paper, we present a technique for automated fault localization that, given a program and an error trace, efficiently narrows down the cause of the error to a few statements. These statements are then ranked in terms of their suspiciousness. Our technique relies only on the semantics of the given program and does not require any test cases or user guidance. In experiments on a set of C benchmarks, we show that our technique is effective in quickly isolating the cause of error while out-performing other state-of-the-art fault-localization techniques.}, author = {Christakis, Maria and Heizmann, Matthias and Mansur, Muhammad Numair and Schilling, Christian and Wüstholz, Valentin}, booktitle = {25th International Conference on Tools and Algorithms for the Construction and Analysis of Systems }, location = {Prague, Czech Republic}, pages = {226--243}, publisher = {Springer Nature}, title = {{Semantic fault localization and suspiciousness ranking}}, doi = {10.1007/978-3-030-17462-0_13}, volume = {11427}, year = {2019}, } @article{6105, abstract = { Hosts can alter their strategy towards pathogens during their lifetime; that is, they can show phenotypic plasticity in immunity or life history. Immune priming is one such example, where a previous encounter with a pathogen confers enhanced protection upon secondary challenge, resulting in reduced pathogen load (i.e., resistance) and improved host survival. However, an initial encounter might also enhance tolerance, particularly to less virulent opportunistic pathogens that establish persistent infections. In this scenario, individuals are better able to reduce the negative fecundity consequences that result from a high pathogen burden. Finally, previous exposure may also lead to life‐history adjustments, such as terminal investment into reproduction. Using different Drosophila melanogaster host genotypes and two bacterial pathogens, Lactococcus lactis and Pseudomonas entomophila, we tested whether previous exposure results in resistance or tolerance and whether it modifies immune gene expression during an acute‐phase infection (one day post‐challenge). We then asked whether previous pathogen exposure affects chronic‐phase pathogen persistence and longer‐term survival (28 days post‐challenge). We predicted that previous exposure would increase host resistance to an early stage bacterial infection while it might come at a cost to host fecundity tolerance. We reasoned that resistance would be due in part to stronger immune gene expression after challenge. We expected that previous exposure would improve long‐term survival, that it would reduce infection persistence, and we expected to find genetic variation in these responses. We found that previous exposure to P. entomophila weakened host resistance to a second infection independent of genotype and had no effect on immune gene expression. Fecundity tolerance showed genotypic variation but was not influenced by previous exposure. However, L. lactis persisted as a chronic infection, whereas survivors cleared the more pathogenic P. entomophila infection. To our knowledge, this is the first study that addresses host tolerance to bacteria in relation to previous exposure, taking a multi‐faceted approach to address the topic. Our results suggest that previous exposure comes with transient costs to resistance during the early stage of infection in this host–pathogen system and that infection persistence may be bacterium‐specific. }, author = {Kutzer, Megan and Kurtz, Joachim and Armitage, Sophie A.O.}, issn = {13652656}, journal = {Journal of Animal Ecology}, publisher = {Wiley}, title = {{A multi-faceted approach testing the effects of previous bacterial exposure on resistance and tolerance}}, doi = {10.1111/1365-2656.12953}, year = {2019}, } @article{6092, abstract = {In 1915, Einstein and de Haas and Barnett demonstrated that changing the magnetization of a magnetic material results in mechanical rotation and vice versa. At the microscopic level, this effect governs the transfer between electron spin and orbital angular momentum, and lattice degrees of freedom, understanding which is key for molecular magnets, nano-magneto-mechanics, spintronics, and ultrafast magnetism. Until now, the timescales of electron-to-lattice angular momentum transfer remain unclear, since modeling this process on a microscopic level requires the addition of an infinite amount of quantum angular momenta. We show that this problem can be solved by reformulating it in terms of the recently discovered angulon quasiparticles, which results in a rotationally invariant quantum many-body theory. In particular, we demonstrate that nonperturbative effects take place even if the electron-phonon coupling is weak and give rise to angular momentum transfer on femtosecond timescales.}, author = {Mentink, Johann H and Katsnelson, Mikhail and Lemeshko, Mikhail}, journal = {Physical Review B}, number = {6}, publisher = {APS}, title = {{Quantum many-body dynamics of the Einstein-de Haas effect}}, doi = {10.1103/PhysRevB.99.064428}, volume = {99}, year = {2019}, } @article{6232, abstract = {The boundary behaviour of solutions of stochastic PDEs with Dirichlet boundary conditions can be surprisingly—and in a sense, arbitrarily—bad: as shown by Krylov[ SIAM J. Math. Anal.34(2003) 1167–1182], for any α>0 one can find a simple 1-dimensional constant coefficient linear equation whose solution at the boundary is not α-Hölder continuous.We obtain a positive counterpart of this: under some mild regularity assumptions on the coefficients, solutions of semilinear SPDEs on C1 domains are proved to be α-Hölder continuous up to the boundary with some α>0.}, author = {Gerencser, Mate}, issn = {00911798}, journal = {Annals of Probability}, number = {2}, pages = {804--834}, publisher = {Institute of Mathematical Statistics}, title = {{Boundary regularity of stochastic PDEs}}, doi = {10.1214/18-AOP1272}, volume = {47}, year = {2019}, } @article{6174, abstract = {We propose a scaling theory for the many-body localization (MBL) phase transition in one dimension, building on the idea that it proceeds via a “quantum avalanche.” We argue that the critical properties can be captured at a coarse-grained level by a Kosterlitz-Thouless (KT) renormalization group (RG) flow. On phenomenological grounds, we identify the scaling variables as the density of thermal regions and the length scale that controls the decay of typical matrix elements. Within this KT picture, the MBL phase is a line of fixed points that terminates at the delocalization transition. We discuss two possible scenarios distinguished by the distribution of rare, fractal thermal inclusions within the MBL phase. In the first scenario, these regions have a stretched exponential distribution in the MBL phase. In the second scenario, the near-critical MBL phase hosts rare thermal regions that are power-law-distributed in size. This points to the existence of a second transition within the MBL phase, at which these power laws change to the stretched exponential form expected at strong disorder. We numerically simulate two different phenomenological RGs previously proposed to describe the MBL transition. Both RGs display a universal power-law length distribution of thermal regions at the transition with a critical exponent αc=2, and continuously varying exponents in the MBL phase consistent with the KT picture.}, author = {Dumitrescu, Philipp T. and Goremykina, Anna and Parameswaran, Siddharth A. and Serbyn, Maksym and Vasseur, Romain}, issn = {2469-9950}, journal = {Physical Review B}, number = {9}, publisher = {American Physical Society (APS)}, title = {{Kosterlitz-Thouless scaling at many-body localization phase transitions}}, doi = {10.1103/physrevb.99.094205}, volume = {99}, year = {2019}, } @article{6465, abstract = {Tight control over protein degradation is a fundamental requirement for cells to respond rapidly to various stimuli and adapt to a fluctuating environment. Here we develop a versatile, easy-to-handle library of destabilizing tags (degrons) for the precise regulation of protein expression profiles in mammalian cells by modulating target protein half-lives in a predictable manner. Using the well-established tetracycline gene-regulation system as a model, we show that the dynamics of protein expression can be tuned by fusing appropriate degron tags to gene regulators. Next, we apply this degron library to tune a synthetic pulse-generating circuit in mammalian cells. With this toolbox we establish a set of pulse generators with tailored pulse lengths and magnitudes of protein expression. This methodology will prove useful in the functional roles of essential proteins, fine-tuning of gene-expression systems, and enabling a higher complexity in the design of synthetic biological systems in mammalian cells.}, author = {Chassin, Hélène and Müller, Marius and Tigges, Marcel and Scheller, Leo and Lang, Moritz and Fussenegger, Martin}, issn = {20411723}, journal = {Nature Communications}, number = {1}, publisher = {Springer Nature}, title = {{A modular degron library for synthetic circuits in mammalian cells}}, doi = {10.1038/s41467-019-09974-5}, volume = {10}, year = {2019}, } @article{6352, abstract = {Chronic overuse of common pharmaceuticals, e.g. acetaminophen (paracetamol), often leads to the development of acute liver failure (ALF). This study aimed to elucidate the effect of cultured mesenchymal stem cells (MSCs) proteome on the onset of liver damage and regeneration dynamics in animals with ALF induced by acetaminophen, to test the liver protective efficacy of MSCs proteome depending on the oxygen tension in cell culture, and to blueprint protein components responsible for the effect. Protein compositions prepared from MSCs cultured in mild hypoxic (5% and 10% O2) and normal (21% O2) conditions were used to treat ALF induced in mice by injection of acetaminophen. To test the effect of reduced oxygen tension in cell culture on resulting MSCs proteome content we applied a combination of high performance liquid chromatography and mass-spectrometry (LC–MS/MS) for the identification of proteins in lysates of MSCs cultured at different O2 levels. The treatment of acetaminophen-administered animals with proteins released from cultured MSCs resulted in the inhibition of inflammatory reactions in damaged liver; the area of hepatocyte necrosis being reduced in the first 24 h. Compositions obtained from MSCs cultured at lower O2 level were shown to be more potent than a composition prepared from normoxic cells. A comparative characterization of protein pattern and identification of individual components done by a cytokine assay and proteomics analysis of protein compositions revealed that even moderate hypoxia produces discrete changes in the expression of various subsets of proteins responsible for intracellular respiration and cell signaling. The application of proteins prepared from MSCs grown in vitro at reduced oxygen tension significantly accelerates healing process in damaged liver tissue. The proteomics data obtained for different preparations offer new information about the potential candidates in the MSCs protein repertoire sensitive to oxygen tension in culture medium, which can be involved in the generalized mechanisms the cells use to respond to acute liver failure.}, author = {Temnov, Andrey Alexandrovich and Rogov, Konstantin Arkadevich and Sklifas, Alla Nikolaevna and Klychnikova, Elena Valerievna and Hartl, Markus and Djinovic-Carugo, Kristina and Charnagalov, Alexej}, issn = {15734978}, journal = {Molecular Biology Reports}, publisher = {Springer}, title = {{Protective properties of the cultured stem cell proteome studied in an animal model of acetaminophen-induced acute liver failure}}, doi = {10.1007/s11033-019-04765-z}, year = {2019}, } @article{6713, abstract = {Evolutionary studies are often limited by missing data that are critical to understanding the history of selection. Selection experiments, which reproduce rapid evolution under controlled conditions, are excellent tools to study how genomes evolve under selection. Here we present a genomic dissection of the Longshanks selection experiment, in which mice were selectively bred over 20 generations for longer tibiae relative to body mass, resulting in 13% longer tibiae in two replicates. We synthesized evolutionary theory, genome sequences and molecular genetics to understand the selection response and found that it involved both polygenic adaptation and discrete loci of major effect, with the strongest loci tending to be selected in parallel between replicates. We show that selection may favor de-repression of bone growth through inactivating two limb enhancers of an inhibitor, Nkx3-2. Our integrative genomic analyses thus show that it is possible to connect individual base-pair changes to the overall selection response.}, author = {Castro, João Pl and Yancoskie, Michelle N. and Marchini, Marta and Belohlavy, Stefanie and Hiramatsu, Layla and Kučka, Marek and Beluch, William H. and Naumann, Ronald and Skuplik, Isabella and Cobb, John and Barton, Nicholas H and Rolian, Campbell and Chan, Yingguang Frank}, journal = {eLife}, publisher = {eLife}, title = {{An integrative genomic analysis of the Longshanks selection experiment for longer limbs in mice}}, doi = {10.7554/eLife.42014}, volume = {8}, 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}, } @article{6566, abstract = {Methodologies that involve the use of nanoparticles as “artificial atoms” to rationally build materials in a bottom-up fashion are particularly well-suited to control the matter at the nanoscale. Colloidal synthetic routes allow for an exquisite control over such “artificial atoms” in terms of size, shape, and crystal phase as well as core and surface compositions. We present here a bottom-up approach to produce Pb–Ag–K–S–Te nanocomposites, which is a highly promising system for thermoelectric energy conversion. First, we developed a high-yield and scalable colloidal synthesis route to uniform lead sulfide (PbS) nanorods, whose tips are made of silver sulfide (Ag2S). We then took advantage of the large surface-to-volume ratio to introduce a p-type dopant (K) by replacing native organic ligands with K2Te. Upon thermal consolidation, K2Te-surface modified PbS–Ag2S nanorods yield p-type doped nanocomposites with PbTe and PbS as major phases and Ag2S and Ag2Te as embedded nanoinclusions. Thermoelectric characterization of such consolidated nanosolids showed a high thermoelectric figure-of-merit of 1 at 620 K.}, author = {Ibáñez, Maria and Genç, Aziz and Hasler, Roger and Liu, Yu and Dobrozhan, Oleksandr and Nazarenko, Olga and Mata, María de la and Arbiol, Jordi and Cabot, Andreu and Kovalenko, Maksym V.}, issn = {1936-086X}, journal = {ACS Nano}, keyword = {colloidal nanoparticles, asymmetric nanoparticles, inorganic ligands, heterostructures, catalyst assisted growth, nanocomposites, thermoelectrics}, number = {6}, pages = {6572--6580}, publisher = {ACS}, title = {{Tuning transport properties in thermoelectric nanocomposites through inorganic ligands and heterostructured building blocks}}, doi = {10.1021/acsnano.9b00346}, volume = {13}, year = {2019}, } @article{6511, abstract = {Let U and V be two independent N by N random matrices that are distributed according to Haar measure on U(N). Let Σ be a nonnegative deterministic N by N matrix. The single ring theorem [Ann. of Math. (2) 174 (2011) 1189–1217] asserts that the empirical eigenvalue distribution of the matrix X:=UΣV∗ converges weakly, in the limit of large N, to a deterministic measure which is supported on a single ring centered at the origin in ℂ. Within the bulk regime, that is, in the interior of the single ring, we establish the convergence of the empirical eigenvalue distribution on the optimal local scale of order N−1/2+ε and establish the optimal convergence rate. The same results hold true when U and V are Haar distributed on O(N).}, author = {Bao, Zhigang and Erdös, László and Schnelli, Kevin}, issn = {00911798}, journal = {Annals of Probability}, number = {3}, pages = {1270--1334}, publisher = {Project Euclid}, title = {{Local single ring theorem on optimal scale}}, doi = {10.1214/18-AOP1284}, volume = {47}, 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}, } @article{6617, abstract = {The effective large-scale properties of materials with random heterogeneities on a small scale are typically determined by the method of representative volumes: a sample of the random material is chosen—the representative volume—and its effective properties are computed by the cell formula. Intuitively, for a fixed sample size it should be possible to increase the accuracy of the method by choosing a material sample which captures the statistical properties of the material particularly well; for example, for a composite material consisting of two constituents, one would select a representative volume in which the volume fraction of the constituents matches closely with their volume fraction in the overall material. Inspired by similar attempts in materials science, Le Bris, Legoll and Minvielle have designed a selection approach for representative volumes which performs remarkably well in numerical examples of linear materials with moderate contrast. In the present work, we provide a rigorous analysis of this selection approach for representative volumes in the context of stochastic homogenization of linear elliptic equations. In particular, we prove that the method essentially never performs worse than a random selection of the material sample and may perform much better if the selection criterion for the material samples is chosen suitably.}, author = {Fischer, Julian L}, journal = {Archive for Rational Mechanics and Analysis}, publisher = {Springer}, title = {{The choice of representative volumes in the approximation of effective properties of random materials}}, doi = {10.1007/s00205-019-01400-w}, 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{6477, abstract = {Thermalizing quantum systems are conventionallydescribed by statistical mechanics at equilib-rium. However, not all systems fall into this category, with many-body localization providinga generic mechanism for thermalization to fail in strongly disordered systems. Many-bodylocalized (MBL) systems remain perfect insulators at nonzero temperature, which do notthermalize and therefore cannot be describedusing statistical mechanics. This Colloquiumreviews recent theoretical and experimental advances in studies of MBL systems, focusing onthe new perspective provided by entanglement and nonequilibrium experimental probes suchas quantum quenches. Theoretically, MBL systems exhibit a new kind of robust integrability: anextensive set of quasilocal integrals of motion emerges, which provides an intuitive explanationof the breakdown of thermalization. A description based on quasilocal integrals of motion isused to predict dynamical properties of MBL systems, such as the spreading of quantumentanglement, the behavior of local observables, and the response to external dissipativeprocesses. Furthermore, MBL systems can exhibit eigenstate transitions and quantum ordersforbidden in thermodynamic equilibrium. An outline isgiven of the current theoretical under-standing of the quantum-to-classical transitionbetween many-body localized and ergodic phasesand anomalous transport in the vicinity of that transition. Experimentally, synthetic quantumsystems, which are well isolated from an external thermal reservoir, provide natural platforms forrealizing the MBL phase. Recent experiments with ultracold atoms, trapped ions, superconductingqubits, and quantum materials, in which different signatures of many-body localization have beenobserved, are reviewed. This Colloquium concludes by listing outstanding challenges andpromising future research directions.}, author = {Abanin, Dmitry A. and Altman, Ehud and Bloch, Immanuel and Serbyn, Maksym}, issn = {0034-6861}, journal = {Reviews of Modern Physics}, number = {2}, publisher = {APS Physics}, title = {{Colloquium: Many-body localization, thermalization, and entanglement}}, doi = {10.1103/revmodphys.91.021001}, volume = {91}, year = {2019}, } @article{6650, abstract = {We propose a novel technique for the automatic design of molds to cast highly complex shapes. The technique generates composite, two-piece molds. Each mold piece is made up of a hard plastic shell and a flexible silicone part. Thanks to the thin, soft, and smartly shaped silicone part, which is kept in place by a hard plastic shell, we can cast objects of unprecedented complexity. An innovative algorithm based on a volumetric analysis defines the layout of the internal cuts in the silicone mold part. Our approach can robustly handle thin protruding features and intertwined topologies that have caused previous methods to fail. We compare our results with state of the art techniques, and we demonstrate the casting of shapes with extremely complex geometry.}, author = {Alderighi, Thomas and Malomo, Luigi and Giorgi, Daniela and Bickel, Bernd and Cignoni, Paolo and Pietroni, Nico}, issn = {0730-0301}, journal = {ACM Transactions on Graphics}, number = {4}, publisher = {ACM}, title = {{Volume-aware design of composite molds}}, doi = {10.1145/3306346.3322981}, volume = {38}, year = {2019}, }