@article{5949, abstract = {Aberrant proteostasis of protein aggregation may lead to behavior disorders including chronic mental illnesses (CMI). Furthermore, the neuronal activity alterations that underlie CMI are not well understood. We recorded the local field potential and single-unit activity of the hippocampal CA1 region in vivo in rats transgenically overexpressing the Disrupted-in-Schizophrenia 1 (DISC1) gene (tgDISC1), modeling sporadic CMI. These tgDISC1 rats have previously been shown to exhibit DISC1 protein aggregation, disturbances in the dopaminergic system and attention-related deficits. Recordings were performed during exploration of familiar and novel open field environments and during sleep, allowing investigation of neuronal abnormalities in unconstrained behavior. Compared to controls, tgDISC1 place cells exhibited smaller place fields and decreased speed-modulation of their firing rates, demonstrating altered spatial coding and deficits in encoding location-independent sensory inputs. Oscillation analyses showed that tgDISC1 pyramidal neurons had higher theta phase locking strength during novelty, limiting their phase coding ability. However, their mean theta phases were more variable at the population level, reducing oscillatory network synchronization. Finally, tgDISC1 pyramidal neurons showed a lack of novelty-induced shift in their preferred theta and gamma firing phases, indicating deficits in coding of novel environments with oscillatory firing. By combining single cell and neuronal population analyses, we link DISC1 protein pathology with abnormal hippocampal neural coding and network synchrony, and thereby gain a more comprehensive understanding of CMI mechanisms.}, author = {Käfer, Karola and Malagon-Vina, Hugo and Dickerson, Desiree and O'Neill, Joseph and Trossbach, Svenja V. and Korth, Carsten and Csicsvari, Jozsef L}, journal = {Hippocampus}, number = {9}, pages = {802--816}, publisher = {Wiley}, title = {{Disrupted-in-schizophrenia 1 overexpression disrupts hippocampal coding and oscillatory synchronization}}, doi = {10.1002/hipo.23076}, volume = {29}, year = {2019}, } @article{5986, abstract = {Given a triangulation of a point set in the plane, a flip deletes an edge e whose removal leaves a convex quadrilateral, and replaces e by the opposite diagonal of the quadrilateral. It is well known that any triangulation of a point set can be reconfigured to any other triangulation by some sequence of flips. We explore this question in the setting where each edge of a triangulation has a label, and a flip transfers the label of the removed edge to the new edge. It is not true that every labelled triangulation of a point set can be reconfigured to every other labelled triangulation via a sequence of flips, but we characterize when this is possible. There is an obvious necessary condition: for each label l, if edge e has label l in the first triangulation and edge f has label l in the second triangulation, then there must be some sequence of flips that moves label l from e to f, ignoring all other labels. Bose, Lubiw, Pathak and Verdonschot formulated the Orbit Conjecture, which states that this necessary condition is also sufficient, i.e. that all labels can be simultaneously mapped to their destination if and only if each label individually can be mapped to its destination. We prove this conjecture. Furthermore, we give a polynomial-time algorithm (with 𝑂(𝑛8) being a crude bound on the run-time) to find a sequence of flips to reconfigure one labelled triangulation to another, if such a sequence exists, and we prove an upper bound of 𝑂(𝑛7) on the length of the flip sequence. Our proof uses the topological result that the sets of pairwise non-crossing edges on a planar point set form a simplicial complex that is homeomorphic to a high-dimensional ball (this follows from a result of Orden and Santos; we give a different proof based on a shelling argument). The dual cell complex of this simplicial ball, called the flip complex, has the usual flip graph as its 1-skeleton. We use properties of the 2-skeleton of the flip complex to prove the Orbit Conjecture.}, author = {Lubiw, Anna and Masárová, Zuzana and Wagner, Uli}, issn = {1432-0444}, journal = {Discrete & Computational Geometry}, number = {4}, pages = {880--898}, publisher = {Springer Nature}, title = {{A proof of the orbit conjecture for flipping edge-labelled triangulations}}, doi = {10.1007/s00454-018-0035-8}, volume = {61}, year = {2019}, } @article{6014, abstract = {Speed of sound waves in gases and liquids are governed by the compressibility of the medium. There exists another type of non-dispersive wave where the wave speed depends on stress instead of elasticity of the medium. A well-known example is the Alfven wave, which propagates through plasma permeated by a magnetic field with the speed determined by magnetic tension. An elastic analogue of Alfven waves has been predicted in a flow of dilute polymer solution where the elastic stress of the stretching polymers determines the elastic wave speed. Here we present quantitative evidence of elastic Alfven waves in elastic turbulence of a viscoelastic creeping flow between two obstacles in channel flow. The key finding in the experimental proof is a nonlinear dependence of the elastic wave speed cel on the Weissenberg number Wi, which deviates from predictions based on a model of linear polymer elasticity.}, author = {Varshney, Atul and Steinberg, Victor}, issn = {2041-1723}, journal = {Nature Communications}, publisher = {Springer Nature}, title = {{Elastic alfven waves in elastic turbulence}}, doi = {10.1038/s41467-019-08551-0}, volume = {10}, 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{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{6025, abstract = {Non-canonical Wnt signaling plays a central role for coordinated cell polarization and directed migration in metazoan development. While spatiotemporally restricted activation of non-canonical Wnt-signaling drives cell polarization in epithelial tissues, it remains unclear whether such instructive activity is also critical for directed mesenchymal cell migration. Here, we developed a light-activated version of the non-canonical Wnt receptor Frizzled 7 (Fz7) to analyze how restricted activation of non-canonical Wnt signaling affects directed anterior axial mesendoderm (prechordal plate, ppl) cell migration within the zebrafish gastrula. We found that Fz7 signaling is required for ppl cell protrusion formation and migration and that spatiotemporally restricted ectopic activation is capable of redirecting their migration. Finally, we show that uniform activation of Fz7 signaling in ppl cells fully rescues defective directed cell migration in fz7 mutant embryos. Together, our findings reveal that in contrast to the situation in epithelial cells, non-canonical Wnt signaling functions permissively rather than instructively in directed mesenchymal cell migration during gastrulation.}, author = {Capek, Daniel and Smutny, Michael and Tichy, Alexandra Madelaine and Morri, Maurizio and Janovjak, Harald L and Heisenberg, Carl-Philipp J}, journal = {eLife}, publisher = {eLife Sciences Publications}, title = {{Light-activated Frizzled7 reveals a permissive role of non-canonical wnt signaling in mesendoderm cell migration}}, doi = {10.7554/eLife.42093}, volume = {8}, 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}, number = {9}, pages = {1983--2005}, publisher = {Wiley}, title = {{A solution theory for quasilinear singular SPDEs}}, doi = {10.1002/cpa.21816}, volume = {72}, year = {2019}, } @article{6029, abstract = {Protein micropatterning has become an important tool for many biomedical applications as well as in academic research. Current techniques that allow to reduce the feature size of patterns below 1 μm are, however, often costly and require sophisticated equipment. We present here a straightforward and convenient method to generate highly condensed nanopatterns of proteins without the need for clean room facilities or expensive equipment. Our approach is based on nanocontact printing and allows for the fabrication of protein patterns with feature sizes of 80 nm and periodicities down to 140 nm. This was made possible by the use of the material X-poly(dimethylsiloxane) (X-PDMS) in a two-layer stamp layout for protein printing. In a proof of principle, different proteins at various scales were printed and the pattern quality was evaluated by atomic force microscopy (AFM) and super-resolution fluorescence microscopy.}, author = {Lindner, Marco and Tresztenyak, Aliz and Fülöp, Gergö and Jahr, Wiebke and Prinz, Adrian and Prinz, Iris and Danzl, Johann G and Schütz, Gerhard J. and Sevcsik, Eva}, issn = {22962646}, journal = {Frontiers in Chemistry}, publisher = {Frontiers Media S.A.}, title = {{A fast and simple contact printing approach to generate 2D protein nanopatterns}}, doi = {10.3389/fchem.2018.00655}, volume = {6}, 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}, keywords = {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{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{6049, abstract = {In this article it is shown that large systems with many interacting units endowing multiple phases display self-oscillations in the presence of linear feedback between the control and order parameters, where an Andronov–Hopf bifurcation takes over the phase transition. This is simply illustrated through the mean field Landau theory whose feedback dynamics turn out to be described by the Van der Pol equation and it is then validated for the fully connected Ising model following heat bath dynamics. Despite its simplicity, this theory accounts potentially for a rich range of phenomena: here it is applied to describe in a stylized way (i) excess demand-price cycles due to strong herding in a simple agent-based market model; (ii) congestion waves in queuing networks triggered by user feedback to delays in overloaded conditions; and (iii) metabolic network oscillations resulting from cell growth control in a bistable phenotypic landscape.}, author = {De Martino, Daniele}, journal = {Journal of Physics A: Mathematical and Theoretical}, number = {4}, publisher = {IOP Publishing}, title = {{Feedback-induced self-oscillations in large interacting systems subjected to phase transitions}}, doi = {10.1088/1751-8121/aaf2dd}, volume = {52}, year = {2019}, } @article{6050, abstract = {We answer a question of David Hilbert: given two circles it is not possible in general to construct their centers using only a straightedge. On the other hand, we give infinitely many families of pairs of circles for which such construction is possible. }, author = {Akopyan, Arseniy and Fedorov, Roman}, journal = {Proceedings of the American Mathematical Society}, pages = {91--102}, publisher = {AMS}, title = {{Two circles and only a straightedge}}, doi = {10.1090/proc/14240}, volume = {147}, year = {2019}, } @article{6052, abstract = {Expansion microscopy is a relatively new approach to super-resolution imaging that uses expandable hydrogels to isotropically increase the physical distance between fluorophores in biological samples such as cell cultures or tissue slices. The classic gel recipe results in an expansion factor of ~4×, with a resolution of 60–80 nm. We have recently developed X10 microscopy, which uses a gel that achieves an expansion factor of ~10×, with a resolution of ~25 nm. Here, we provide a step-by-step protocol for X10 expansion microscopy. A typical experiment consists of seven sequential stages: (i) immunostaining, (ii) anchoring, (iii) polymerization, (iv) homogenization, (v) expansion, (vi) imaging, and (vii) validation. The protocol presented here includes recommendations for optimization, pitfalls and their solutions, and detailed guidelines that should increase reproducibility. Although our protocol focuses on X10 expansion microscopy, we detail which of these suggestions are also applicable to classic fourfold expansion microscopy. We exemplify our protocol using primary hippocampal neurons from rats, but our approach can be used with other primary cells or cultured cell lines of interest. This protocol will enable any researcher with basic experience in immunostainings and access to an epifluorescence microscope to perform super-resolution microscopy with X10. The procedure takes 3 d and requires ~5 h of actively handling the sample for labeling and expansion, and another ~3 h for imaging and analysis.}, author = {Truckenbrodt, Sven M and Sommer, Christoph M and Rizzoli, Silvio O and Danzl, Johann G}, journal = {Nature Protocols}, number = {3}, pages = {832–863}, publisher = {Nature Publishing Group}, title = {{A practical guide to optimization in X10 expansion microscopy}}, doi = {10.1038/s41596-018-0117-3}, volume = {14}, 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}, issn = {1748-3395}, journal = {Nature Nanotechnology}, number = {4}, pages = {334–339}, publisher = {Springer Nature}, title = {{Quantum electromechanics of a hypersonic crystal}}, doi = {10.1038/s41565-019-0377-2}, volume = {14}, year = {2019}, } @inproceedings{6056, abstract = {In today's programmable blockchains, smart contracts are limited to being deterministic and non-probabilistic. This lack of randomness is a consequential limitation, given that a wide variety of real-world financial contracts, such as casino games and lotteries, depend entirely on randomness. As a result, several ad-hoc random number generation approaches have been developed to be used in smart contracts. These include ideas such as using an oracle or relying on the block hash. However, these approaches are manipulatable, i.e. their output can be tampered with by parties who might not be neutral, such as the owner of the oracle or the miners.We propose a novel game-theoretic approach for generating provably unmanipulatable pseudorandom numbers on the blockchain. Our approach allows smart contracts to access a trustworthy source of randomness that does not rely on potentially compromised miners or oracles, hence enabling the creation of a new generation of smart contracts that are not limited to being non-probabilistic and can be drawn from the much more general class of probabilistic programs.}, author = {Chatterjee, Krishnendu and Goharshady, Amir Kafshdar and Pourdamghani, Arash}, booktitle = {IEEE International Conference on Blockchain and Cryptocurrency}, location = {Seoul, Korea}, publisher = {IEEE}, title = {{Probabilistic smart contracts: Secure randomness on the blockchain}}, doi = {10.1109/BLOC.2019.8751326}, year = {2019}, } @misc{6060, author = {Vicoso, Beatriz}, publisher = {Institute of Science and Technology Austria}, title = {{Supplementary data for "Sex-biased gene expression and dosage compensation on the Artemia franciscana Z-chromosome" (Huylman, Toups et al., 2019). }}, doi = {10.15479/AT:ISTA:6060}, year = {2019}, } @misc{6062, abstract = {Open the files in Jupyter Notebook (reccomended https://www.anaconda.com/distribution/#download-section with Python 3.7).}, author = {Nardin, Michele}, publisher = {Institute of Science and Technology Austria}, title = {{Supplementary Code and Data for the paper "The Entorhinal Cognitive Map is Attracted to Goals"}}, doi = {10.15479/AT:ISTA:6062}, year = {2019}, } @article{6069, abstract = {Electron transport in two-dimensional conducting materials such as graphene, with dominant electron–electron interaction, exhibits unusual vortex flow that leads to a nonlocal current-field relation (negative resistance), distinct from the classical Ohm’s law. The transport behavior of these materials is best described by low Reynolds number hydrodynamics, where the constitutive pressure–speed relation is Stoke’s law. Here we report evidence of such vortices observed in a viscous flow of Newtonian fluid in a microfluidic device consisting of a rectangular cavity—analogous to the electronic system. We extend our experimental observations to elliptic cavities of different eccentricities, and validate them by numerically solving bi-harmonic equation obtained for the viscous flow with no-slip boundary conditions. We verify the existence of a predicted threshold at which vortices appear. Strikingly, we find that a two-dimensional theoretical model captures the essential features of three-dimensional Stokes flow in experiments.}, author = {Mayzel, Jonathan and Steinberg, Victor and Varshney, Atul}, issn = {2041-1723}, journal = {Nature Communications}, publisher = {Springer Nature}, title = {{Stokes flow analogous to viscous electron current in graphene}}, doi = {10.1038/s41467-019-08916-5}, volume = {10}, year = {2019}, } @phdthesis{6071, abstract = {Transcription factors, by binding to specific sequences on the DNA, control the precise spatio-temporal expression of genes inside a cell. However, this specificity is limited, leading to frequent incorrect binding of transcription factors that might have deleterious consequences on the cell. By constructing a biophysical model of TF-DNA binding in the context of gene regulation, I will first explore how regulatory constraints can strongly shape the distribution of a population in sequence space. Then, by directly linking this to a picture of multiple types of transcription factors performing their functions simultaneously inside the cell, I will explore the extent of regulatory crosstalk -- incorrect binding interactions between transcription factors and binding sites that lead to erroneous regulatory states -- and understand the constraints this places on the design of regulatory systems. I will then develop a generic theoretical framework to investigate the coevolution of multiple transcription factors and multiple binding sites, in the context of a gene regulatory network that performs a certain function. As a particular tractable version of this problem, I will consider the evolution of two transcription factors when they transmit upstream signals to downstream target genes. Specifically, I will describe the evolutionary steady states and the evolutionary pathways involved, along with their timescales, of a system that initially undergoes a transcription factor duplication event. To connect this important theoretical model to the prominent biological event of transcription factor duplication giving rise to paralogous families, I will then describe a bioinformatics analysis of C2H2 Zn-finger transcription factors, a major family in humans, and focus on the patterns of evolution that paralogs have undergone in their various protein domains in the recent past. }, author = {Prizak, Roshan}, issn = {2663-337X}, pages = {189}, publisher = {Institute of Science and Technology Austria}, title = {{Coevolution of transcription factors and their binding sites in sequence space}}, doi = {10.15479/at:ista:th6071}, year = {2019}, }