@article{7340, abstract = {Coupling of endoplasmic reticulum stress to dimerisation‑dependent activation of the UPR transducer IRE1 is incompletely understood. Whilst the luminal co-chaperone ERdj4 promotes a complex between the Hsp70 BiP and IRE1's stress-sensing luminal domain (IRE1LD) that favours the latter's monomeric inactive state and loss of ERdj4 de-represses IRE1, evidence linking these cellular and in vitro observations is presently lacking. We report that enforced loading of endogenous BiP onto endogenous IRE1α repressed UPR signalling in CHO cells and deletions in the IRE1α locus that de-repressed the UPR in cells, encode flexible regions of IRE1LD that mediated BiP‑induced monomerisation in vitro. Changes in the hydrogen exchange mass spectrometry profile of IRE1LD induced by ERdj4 and BiP confirmed monomerisation and were consistent with active destabilisation of the IRE1LD dimer. Together, these observations support a competition model whereby waning ER stress passively partitions ERdj4 and BiP to IRE1LD to initiate active repression of UPR signalling.}, author = {Amin-Wetzel, Niko Paresh and Neidhardt, Lisa and Yan, Yahui and Mayer, Matthias P. and Ron, David}, issn = {2050084X}, journal = {eLife}, publisher = {eLife Sciences Publications}, title = {{Unstructured regions in IRE1α specify BiP-mediated destabilisation of the luminal domain dimer and repression of the UPR}}, doi = {10.7554/eLife.50793}, volume = {8}, year = {2019}, } @article{7422, abstract = {Biochemical reactions often occur at low copy numbers but at once in crowded and diverse environments. Space and stochasticity therefore play an essential role in biochemical networks. Spatial-stochastic simulations have become a prominent tool for understanding how stochasticity at the microscopic level influences the macroscopic behavior of such systems. While particle-based models guarantee the level of detail necessary to accurately describe the microscopic dynamics at very low copy numbers, the algorithms used to simulate them typically imply trade-offs between computational efficiency and biochemical accuracy. eGFRD (enhanced Green’s Function Reaction Dynamics) is an exact algorithm that evades such trade-offs by partitioning the N-particle system into M ≤ N analytically tractable one- and two-particle systems; the analytical solutions (Green’s functions) then are used to implement an event-driven particle-based scheme that allows particles to make large jumps in time and space while retaining access to their state variables at arbitrary simulation times. Here we present “eGFRD2,” a new eGFRD version that implements the principle of eGFRD in all dimensions, thus enabling efficient particle-based simulation of biochemical reaction-diffusion processes in the 3D cytoplasm, on 2D planes representing membranes, and on 1D elongated cylinders representative of, e.g., cytoskeletal tracks or DNA; in 1D, it also incorporates convective motion used to model active transport. We find that, for low particle densities, eGFRD2 is up to 6 orders of magnitude faster than conventional Brownian dynamics. We exemplify the capabilities of eGFRD2 by simulating an idealized model of Pom1 gradient formation, which involves 3D diffusion, active transport on microtubules, and autophosphorylation on the membrane, confirming recent experimental and theoretical results on this system to hold under genuinely stochastic conditions.}, author = {Sokolowski, Thomas R and Paijmans, Joris and Bossen, Laurens and Miedema, Thomas and Wehrens, Martijn and Becker, Nils B. and Kaizu, Kazunari and Takahashi, Koichi and Dogterom, Marileen and ten Wolde, Pieter Rein}, issn = {1089-7690}, journal = {The Journal of Chemical Physics}, number = {5}, publisher = {AIP Publishing}, title = {{eGFRD in all dimensions}}, doi = {10.1063/1.5064867}, volume = {150}, year = {2019}, } @inproceedings{7230, abstract = {Simple drawings of graphs are those in which each pair of edges share at most one point, either a common endpoint or a proper crossing. In this paper we study the problem of extending a simple drawing D(G) of a graph G by inserting a set of edges from the complement of G into D(G) such that the result is a simple drawing. In the context of rectilinear drawings, the problem is trivial. For pseudolinear drawings, the existence of such an extension follows from Levi’s enlargement lemma. In contrast, we prove that deciding if a given set of edges can be inserted into a simple drawing is NP-complete. Moreover, we show that the maximization version of the problem is APX-hard. We also present a polynomial-time algorithm for deciding whether one edge uv can be inserted into D(G) when {u,v} is a dominating set for the graph G.}, author = {Arroyo Guevara, Alan M and Derka, Martin and Parada, Irene}, booktitle = {27th International Symposium on Graph Drawing and Network Visualization}, isbn = {978-3-0303-5801-3}, issn = {1611-3349}, location = {Prague, Czech Republic}, pages = {230--243}, publisher = {Springer Nature}, title = {{Extending simple drawings}}, doi = {10.1007/978-3-030-35802-0_18}, volume = {11904}, year = {2019}, } @inproceedings{7232, abstract = {We present Mixed-time Signal Temporal Logic (STL−MX), a specification formalism which extends STL by capturing the discrete/ continuous time duality found in many cyber-physical systems (CPS), as well as mixed-signal electronic designs. In STL−MX, properties of components with continuous dynamics are expressed in STL, while specifications of components with discrete dynamics are written in LTL. To combine the two layers, we evaluate formulas on two traces, discrete- and continuous-time, and introduce two interface operators that map signals, properties and their satisfaction signals across the two time domains. We show that STL-mx has the expressive power of STL supplemented with an implicit T-periodic clock signal. We develop and implement an algorithm for monitoring STL-mx formulas and illustrate the approach using a mixed-signal example. }, author = {Ferrere, Thomas and Maler, Oded and Nickovic, Dejan}, booktitle = {17th International Conference on Formal Modeling and Analysis of Timed Systems}, isbn = {978-3-0302-9661-2}, issn = {1611-3349}, location = {Amsterdam, The Netherlands}, pages = {59--75}, publisher = {Springer Nature}, title = {{Mixed-time signal temporal logic}}, doi = {10.1007/978-3-030-29662-9_4}, volume = {11750}, year = {2019}, } @article{7420, abstract = {β1-integrins mediate cell–matrix interactions and their trafficking is important in the dynamic regulation of cell adhesion, migration and malignant processes, including cancer cell invasion. Here, we employ an RNAi screen to characterize regulators of integrin traffic and identify the association of Golgi-localized gamma ear-containing Arf-binding protein 2 (GGA2) with β1-integrin, and its role in recycling of active but not inactive β1-integrin receptors. Silencing of GGA2 limits active β1-integrin levels in focal adhesions and decreases cancer cell migration and invasion, which is in agreement with its ability to regulate the dynamics of active integrins. By using the proximity-dependent biotin identification (BioID) method, we identified two RAB family small GTPases, i.e. RAB13 and RAB10, as novel interactors of GGA2. Functionally, RAB13 silencing triggers the intracellular accumulation of active β1-integrin, and reduces integrin activity in focal adhesions and cell migration similarly to GGA2 depletion, indicating that both facilitate active β1-integrin recycling to the plasma membrane. Thus, GGA2 and RAB13 are important specificity determinants for integrin activity-dependent traffic.}, author = {Sahgal, Pranshu and Alanko, Jonna H and Icha, Jaroslav and Paatero, Ilkka and Hamidi, Hellyeh and Arjonen, Antti and Pietilä, Mika and Rokka, Anne and Ivaska, Johanna}, issn = {1477-9137}, journal = {Journal of Cell Science}, number = {11}, publisher = {The Company of Biologists}, title = {{GGA2 and RAB13 promote activity-dependent β1-integrin recycling}}, doi = {10.1242/jcs.233387}, volume = {132}, year = {2019}, } @article{7423, abstract = {We compare finite rank perturbations of the following three ensembles of complex rectangular random matrices: First, a generalised Wishart ensemble with one random and two fixed correlation matrices introduced by Borodin and Péché, second, the product of two independent random matrices where one has correlated entries, and third, the case when the two random matrices become also coupled through a fixed matrix. The singular value statistics of all three ensembles is shown to be determinantal and we derive double contour integral representations for their respective kernels. Three different kernels are found in the limit of infinite matrix dimension at the origin of the spectrum. They depend on finite rank perturbations of the correlation and coupling matrices and are shown to be integrable. The first kernel (I) is found for two independent matrices from the second, and two weakly coupled matrices from the third ensemble. It generalises the Meijer G-kernel for two independent and uncorrelated matrices. The third kernel (III) is obtained for the generalised Wishart ensemble and for two strongly coupled matrices. It further generalises the perturbed Bessel kernel of Desrosiers and Forrester. Finally, kernel (II), found for the ensemble of two coupled matrices, provides an interpolation between the kernels (I) and (III), generalising previous findings of part of the authors.}, author = {Akemann, Gernot and Checinski, Tomasz and Liu, Dangzheng and Strahov, Eugene}, issn = {0246-0203}, journal = {Annales de l'Institut Henri Poincaré, Probabilités et Statistiques}, number = {1}, pages = {441--479}, publisher = {Institute of Mathematical Statistics}, title = {{Finite rank perturbations in products of coupled random matrices: From one correlated to two Wishart ensembles}}, doi = {10.1214/18-aihp888}, volume = {55}, year = {2019}, } @article{7421, abstract = {X and Y chromosomes can diverge when rearrangements block recombination between them. Here we present the first genomic view of a reciprocal translocation that causes two physically unconnected pairs of chromosomes to be coinherited as sex chromosomes. In a population of the common frog (Rana temporaria), both pairs of X and Y chromosomes show extensive sequence differentiation, but not degeneration of the Y chromosomes. A new method based on gene trees shows both chromosomes are sex‐linked. Furthermore, the gene trees from the two Y chromosomes have identical topologies, showing they have been coinherited since the reciprocal translocation occurred. Reciprocal translocations can thus reshape sex linkage on a much greater scale compared with inversions, the type of rearrangement that is much better known in sex chromosome evolution, and they can greatly amplify the power of sexually antagonistic selection to drive genomic rearrangement. Two more populations show evidence of other rearrangements, suggesting that this species has unprecedented structural polymorphism in its sex chromosomes.}, author = {Toups, Melissa A and Rodrigues, Nicolas and Perrin, Nicolas and Kirkpatrick, Mark}, issn = {1365-294X}, journal = {Molecular Ecology}, number = {8}, pages = {1877--1889}, publisher = {Wiley}, title = {{A reciprocal translocation radically reshapes sex‐linked inheritance in the common frog}}, doi = {10.1111/mec.14990}, volume = {28}, year = {2019}, } @inproceedings{7411, abstract = {Proofs of sequential work (PoSW) are proof systems where a prover, upon receiving a statement χ and a time parameter T computes a proof ϕ(χ,T) which is efficiently and publicly verifiable. The proof can be computed in T sequential steps, but not much less, even by a malicious party having large parallelism. A PoSW thus serves as a proof that T units of time have passed since χ was received. PoSW were introduced by Mahmoody, Moran and Vadhan [MMV11], a simple and practical construction was only recently proposed by Cohen and Pietrzak [CP18]. In this work we construct a new simple PoSW in the random permutation model which is almost as simple and efficient as [CP18] but conceptually very different. Whereas the structure underlying [CP18] is a hash tree, our construction is based on skip lists and has the interesting property that computing the PoSW is a reversible computation. The fact that the construction is reversible can potentially be used for new applications like constructing proofs of replication. We also show how to “embed” the sloth function of Lenstra and Weselowski [LW17] into our PoSW to get a PoSW where one additionally can verify correctness of the output much more efficiently than recomputing it (though recent constructions of “verifiable delay functions” subsume most of the applications this construction was aiming at).}, author = {Abusalah, Hamza M and Kamath Hosdurg, Chethan and Klein, Karen and Pietrzak, Krzysztof Z and Walter, Michael}, booktitle = {Advances in Cryptology – EUROCRYPT 2019}, isbn = {9783030176556}, issn = {1611-3349}, location = {Darmstadt, Germany}, pages = {277--291}, publisher = {Springer International Publishing}, title = {{Reversible proofs of sequential work}}, doi = {10.1007/978-3-030-17656-3_10}, volume = {11477}, year = {2019}, } @article{7406, abstract = {Background Synaptic vesicles (SVs) are an integral part of the neurotransmission machinery, and isolation of SVs from their host neuron is necessary to reveal their most fundamental biochemical and functional properties in in vitro assays. Isolated SVs from neurons that have been genetically engineered, e.g. to introduce genetically encoded indicators, are not readily available but would permit new insights into SV structure and function. Furthermore, it is unclear if cultured neurons can provide sufficient starting material for SV isolation procedures. New method Here, we demonstrate an efficient ex vivo procedure to obtain functional SVs from cultured rat cortical neurons after genetic engineering with a lentivirus. Results We show that ∼108 plated cortical neurons allow isolation of suitable SV amounts for functional analysis and imaging. We found that SVs isolated from cultured neurons have neurotransmitter uptake comparable to that of SVs isolated from intact cortex. Using total internal reflection fluorescence (TIRF) microscopy, we visualized an exogenous SV-targeted marker protein and demonstrated the high efficiency of SV modification. Comparison with existing methods Obtaining SVs from genetically engineered neurons currently generally requires the availability of transgenic animals, which is constrained by technical (e.g. cost and time) and biological (e.g. developmental defects and lethality) limitations. Conclusions These results demonstrate the modification and isolation of functional SVs using cultured neurons and viral transduction. The ability to readily obtain SVs from genetically engineered neurons will permit linking in situ studies to in vitro experiments in a variety of genetic contexts.}, author = {Mckenzie, Catherine and Spanova, Miroslava and Johnson, Alexander J and Kainrath, Stephanie and Zheden, Vanessa and Sitte, Harald H. and Janovjak, Harald L}, issn = {0165-0270}, journal = {Journal of Neuroscience Methods}, pages = {114--121}, publisher = {Elsevier}, title = {{Isolation of synaptic vesicles from genetically engineered cultured neurons}}, doi = {10.1016/j.jneumeth.2018.11.018}, volume = {312}, year = {2019}, } @inproceedings{7437, abstract = {Most of today's distributed machine learning systems assume reliable networks: whenever two machines exchange information (e.g., gradients or models), the network should guarantee the delivery of the message. At the same time, recent work exhibits the impressive tolerance of machine learning algorithms to errors or noise arising from relaxed communication or synchronization. In this paper, we connect these two trends, and consider the following question: Can we design machine learning systems that are tolerant to network unreliability during training? With this motivation, we focus on a theoretical problem of independent interest-given a standard distributed parameter server architecture, if every communication between the worker and the server has a non-zero probability p of being dropped, does there exist an algorithm that still converges, and at what speed? The technical contribution of this paper is a novel theoretical analysis proving that distributed learning over unreliable network can achieve comparable convergence rate to centralized or distributed learning over reliable networks. Further, we prove that the influence of the packet drop rate diminishes with the growth of the number of parameter servers. We map this theoretical result onto a real-world scenario, training deep neural networks over an unreliable network layer, and conduct network simulation to validate the system improvement by allowing the networks to be unreliable.}, author = {Yu, Chen and Tang, Hanlin and Renggli, Cedric and Kassing, Simon and Singla, Ankit and Alistarh, Dan-Adrian and Zhang, Ce and Liu, Ji}, booktitle = {36th International Conference on Machine Learning, ICML 2019}, isbn = {9781510886988}, location = {Long Beach, CA, United States}, pages = {12481--12512}, publisher = {IMLS}, title = {{Distributed learning over unreliable networks}}, volume = {2019-June}, year = {2019}, } @article{7412, abstract = {We develop a framework for the rigorous analysis of focused stochastic local search algorithms. These algorithms search a state space by repeatedly selecting some constraint that is violated in the current state and moving to a random nearby state that addresses the violation, while (we hope) not introducing many new violations. An important class of focused local search algorithms with provable performance guarantees has recently arisen from algorithmizations of the Lovász local lemma (LLL), a nonconstructive tool for proving the existence of satisfying states by introducing a background measure on the state space. While powerful, the state transitions of algorithms in this class must be, in a precise sense, perfectly compatible with the background measure. In many applications this is a very restrictive requirement, and one needs to step outside the class. Here we introduce the notion of measure distortion and develop a framework for analyzing arbitrary focused stochastic local search algorithms, recovering LLL algorithmizations as the special case of no distortion. Our framework takes as input an arbitrary algorithm of such type and an arbitrary probability measure and shows how to use the measure as a yardstick of algorithmic progress, even for algorithms designed independently of the measure.}, author = {Achlioptas, Dimitris and Iliopoulos, Fotis and Kolmogorov, Vladimir}, issn = {1095-7111}, journal = {SIAM Journal on Computing}, number = {5}, pages = {1583--1602}, publisher = {SIAM}, title = {{A local lemma for focused stochastical algorithms}}, doi = {10.1137/16m109332x}, volume = {48}, year = {2019}, } @article{7418, abstract = {Multiple importance sampling (MIS) has become an indispensable tool in Monte Carlo rendering, widely accepted as a near-optimal solution for combining different sampling techniques. But an MIS combination, using the common balance or power heuristics, often results in an overly defensive estimator, leading to high variance. We show that by generalizing the MIS framework, variance can be substantially reduced. Specifically, we optimize one of the combined sampling techniques so as to decrease the overall variance of the resulting MIS estimator. We apply the approach to the computation of direct illumination due to an HDR environment map and to the computation of global illumination using a path guiding algorithm. The implementation can be as simple as subtracting a constant value from the tabulated sampling density done entirely in a preprocessing step. This produces a consistent noise reduction in all our tests with no negative influence on run time, no artifacts or bias, and no failure cases.}, author = {Karlík, Ondřej and Šik, Martin and Vévoda, Petr and Skrivan, Tomas and Křivánek, Jaroslav}, issn = {1557-7368}, journal = {ACM Transactions on Graphics}, number = {6}, publisher = {ACM}, title = {{MIS compensation: Optimizing sampling techniques in multiple importance sampling}}, doi = {10.1145/3355089.3356565}, volume = {38}, year = {2019}, } @article{7413, abstract = {We consider Bose gases consisting of N particles trapped in a box with volume one and interacting through a repulsive potential with scattering length of order N−1 (Gross–Pitaevskii regime). We determine the ground state energy and the low-energy excitation spectrum, up to errors vanishing as N→∞. Our results confirm Bogoliubov’s predictions.}, author = {Boccato, Chiara and Brennecke, Christian and Cenatiempo, Serena and Schlein, Benjamin}, issn = {1871-2509}, journal = {Acta Mathematica}, number = {2}, pages = {219--335}, publisher = {International Press of Boston}, title = {{Bogoliubov theory in the Gross–Pitaevskii limit}}, doi = {10.4310/acta.2019.v222.n2.a1}, volume = {222}, year = {2019}, } @article{7393, abstract = {The study of parallel ecological divergence provides important clues to the operation of natural selection. Parallel divergence often occurs in heterogeneous environments with different kinds of environmental gradients in different locations, but the genomic basis underlying this process is unknown. We investigated the genomics of rapid parallel adaptation in the marine snail Littorina saxatilis in response to two independent environmental axes (crab-predation versus wave-action and low-shore versus high-shore). Using pooled whole-genome resequencing, we show that sharing of genomic regions of high differentiation between environments is generally low but increases at smaller spatial scales. We identify different shared genomic regions of divergence for each environmental axis and show that most of these regions overlap with candidate chromosomal inversions. Several inversion regions are divergent and polymorphic across many localities. We argue that chromosomal inversions could store shared variation that fuels rapid parallel adaptation to heterogeneous environments, possibly as balanced polymorphism shared by adaptive gene flow.}, author = {Morales, Hernán E. and Faria, Rui and Johannesson, Kerstin and Larsson, Tomas and Panova, Marina and Westram, Anja M and Butlin, Roger K.}, issn = {2375-2548}, journal = {Science Advances}, number = {12}, publisher = {AAAS}, title = {{Genomic architecture of parallel ecological divergence: Beyond a single environmental contrast}}, doi = {10.1126/sciadv.aav9963}, volume = {5}, year = {2019}, } @article{7397, abstract = {Polymer additives can substantially reduce the drag of turbulent flows and the upperlimit, the so called “maximum drag reduction” (MDR) asymptote is universal, i.e. inde-pendent of the type of polymer and solvent used. Until recently, the consensus was that,in this limit, flows are in a marginal state where only a minimal level of turbulence activ-ity persists. Observations in direct numerical simulations using minimal sized channelsappeared to support this view and reported long “hibernation” periods where turbu-lence is marginalized. In simulations of pipe flow we find that, indeed, with increasingWeissenberg number (Wi), turbulence expresses long periods of hibernation if the domainsize is small. However, with increasing pipe length, the temporal hibernation continuouslyalters to spatio-temporal intermittency and here the flow consists of turbulent puffs sur-rounded by laminar flow. Moreover, upon an increase in Wi, the flow fully relaminarises,in agreement with recent experiments. At even larger Wi, a different instability is en-countered causing a drag increase towards MDR. Our findings hence link earlier minimalflow unit simulations with recent experiments and confirm that the addition of polymersinitially suppresses Newtonian turbulence and leads to a reverse transition. The MDRstate on the other hand results from a separate instability and the underlying dynamicscorresponds to the recently proposed state of elasto-inertial-turbulence (EIT).}, author = {Lopez Alonso, Jose M and Choueiri, George H and Hof, Björn}, issn = {1469-7645}, journal = {Journal of Fluid Mechanics}, pages = {699--719}, publisher = {CUP}, title = {{Dynamics of viscoelastic pipe flow at low Reynolds numbers in the maximum drag reduction limit}}, doi = {10.1017/jfm.2019.486}, volume = {874}, year = {2019}, } @article{5678, abstract = {The order-k Voronoi tessellation of a locally finite set 𝑋⊆ℝ𝑛 decomposes ℝ𝑛 into convex domains whose points have the same k nearest neighbors in X. Assuming X is a stationary Poisson point process, we give explicit formulas for the expected number and total area of faces of a given dimension per unit volume of space. We also develop a relaxed version of discrete Morse theory and generalize by counting only faces, for which the k nearest points in X are within a given distance threshold.}, author = {Edelsbrunner, Herbert and Nikitenko, Anton}, issn = {14320444}, journal = {Discrete and Computational Geometry}, number = {4}, pages = {865–878}, publisher = {Springer}, title = {{Poisson–Delaunay Mosaics of Order k}}, doi = {10.1007/s00454-018-0049-2}, volume = {62}, year = {2019}, } @article{5828, abstract = {Hippocampus is needed for both spatial working and reference memories. Here, using a radial eight-arm maze, we examined how the combined demand on these memories influenced CA1 place cell assemblies while reference memories were partially updated. This was contrasted with control tasks requiring only working memory or the update of reference memory. Reference memory update led to the reward-directed place field shifts at newly rewarded arms and to the gradual strengthening of firing in passes between newly rewarded arms but not between those passes that included a familiar-rewarded arm. At the maze center, transient network synchronization periods preferentially replayed trajectories of the next chosen arm in reference memory tasks but the previously visited arm in the working memory task. Hence, reference memory demand was uniquely associated with a gradual, goal novelty-related reorganization of place cell assemblies and with trajectory replay that reflected the animal's decision of which arm to visit next.}, author = {Xu, Haibing and Baracskay, Peter and O'Neill, Joseph and Csicsvari, Jozsef L}, issn = {10974199}, journal = {Neuron}, number = {1}, pages = {119--132.e4}, publisher = {Elsevier}, title = {{Assembly responses of hippocampal CA1 place cells predict learned behavior in goal-directed spatial tasks on the radial eight-arm maze}}, doi = {10.1016/j.neuron.2018.11.015}, volume = {101}, year = {2019}, } @article{5856, abstract = {We give a bound on the ground-state energy of a system of N non-interacting fermions in a three-dimensional cubic box interacting with an impurity particle via point interactions. We show that the change in energy compared to the system in the absence of the impurity is bounded in terms of the gas density and the scattering length of the interaction, independently of N. Our bound holds as long as the ratio of the mass of the impurity to the one of the gas particles is larger than a critical value m∗ ∗≈ 0.36 , which is the same regime for which we recently showed stability of the system.}, author = {Moser, Thomas and Seiringer, Robert}, issn = {14240637}, journal = {Annales Henri Poincare}, number = {4}, pages = {1325–1365}, publisher = {Springer}, title = {{Energy contribution of a point-interacting impurity in a Fermi gas}}, doi = {10.1007/s00023-018-00757-0}, volume = {20}, year = {2019}, } @phdthesis{6957, abstract = {In many shear flows like pipe flow, plane Couette flow, plane Poiseuille flow, etc. turbulence emerges subcritically. Here, when subjected to strong enough perturbations, the flow becomes turbulent in spite of the laminar base flow being linearly stable. The nature of this instability has puzzled the scientific community for decades. At onset, turbulence appears in localized patches and flows are spatio-temporally intermittent. In pipe flow the localized turbulent structures are referred to as puffs and in planar flows like plane Couette and channel flow, patches arise in the form of localized oblique bands. In this thesis, we study the onset of turbulence in channel flow in direct numerical simulations from a dynamical system theory perspective, as well as by performing experiments in a large aspect ratio channel. The aim of the experimental work is to determine the critical Reynolds number where turbulence first becomes sustained. Recently, the onset of turbulence has been described in analogy to absorbing state phase transition (i.e. directed percolation). In particular, it has been shown that the critical point can be estimated from the competition between spreading and decay processes. Here, by performing experiments, we identify the mechanisms underlying turbulence proliferation in channel flow and find the critical Reynolds number, above which turbulence becomes sustained. Above the critical point, the continuous growth at the tip of the stripes outweighs the stochastic shedding of turbulent patches at the tail and the stripes expand. For growing stripes, the probability to decay decreases while the probability of stripe splitting increases. Consequently, and unlike for the puffs in pipe flow, neither of these two processes is time-independent i.e. memoryless. Coupling between stripe expansion and creation of new stripes via splitting leads to a significantly lower critical point ($Re_c=670+/-10$) than most earlier studies suggest. While the above approach sheds light on how turbulence first becomes sustained, it provides no insight into the origin of the stripes themselves. In the numerical part of the thesis we investigate how turbulent stripes form from invariant solutions of the Navier-Stokes equations. The origin of these turbulent stripes can be identified by applying concepts from the dynamical system theory. In doing so, we identify the exact coherent structures underlying stripes and their bifurcations and how they give rise to the turbulent attractor in phase space. We first report a family of localized nonlinear traveling wave solutions of the Navier-Stokes equations in channel flow. These solutions show structural similarities with turbulent stripes in experiments like obliqueness, quasi-streamwise streaks and vortices, etc. A parametric study of these traveling wave solution is performed, with parameters like Reynolds number, stripe tilt angle and domain size, including the stability of the solutions. These solutions emerge through saddle-node bifurcations and form a phase space skeleton for the turbulent stripes observed in the experiments. The lower branches of these TW solutions at different tilt angles undergo Hopf bifurcation and new solutions branches of relative periodic orbits emerge. These RPO solutions do not belong to the same family and therefore the routes to chaos for different angles are different. In shear flows, turbulence at onset is transient in nature. Consequently,turbulence can not be tracked to lower Reynolds numbers, where the dynamics may simplify. Before this happens, turbulence becomes short-lived and laminarizes. In the last part of the thesis, we show that using numerical simulations we can continue turbulent stripes in channel flow past the 'relaminarization barrier' all the way to their origin. Here, turbulent stripe dynamics simplifies and the fluctuations are no longer stochastic and the stripe settles down to a relative periodic orbit. This relative periodic orbit originates from the aforementioned traveling wave solutions. Starting from the relative periodic orbit, a small increase in speed i.e. Reynolds number gives rise to chaos and the attractor dimension sharply increases in contrast to the classical transition scenario where the instabilities affect the flow globally and give rise to much more gradual route to turbulence.}, author = {Paranjape, Chaitanya S}, issn = {2663-337X}, keywords = {Instabilities, Turbulence, Nonlinear dynamics}, pages = {138}, publisher = {Institute of Science and Technology Austria}, title = {{Onset of turbulence in plane Poiseuille flow}}, doi = {10.15479/AT:ISTA:6957}, year = {2019}, } @article{6182, abstract = {We consider large random matrices with a general slowly decaying correlation among its entries. We prove universality of the local eigenvalue statistics and optimal local laws for the resolvent away from the spectral edges, generalizing the recent result of Ajanki et al. [‘Stability of the matrix Dyson equation and random matrices with correlations’, Probab. Theory Related Fields 173(1–2) (2019), 293–373] to allow slow correlation decay and arbitrary expectation. The main novel tool is a systematic diagrammatic control of a multivariate cumulant expansion.}, author = {Erdös, László and Krüger, Torben H and Schröder, Dominik J}, issn = {20505094}, journal = {Forum of Mathematics, Sigma}, publisher = {Cambridge University Press}, title = {{Random matrices with slow correlation decay}}, doi = {10.1017/fms.2019.2}, volume = {7}, year = {2019}, } @article{6186, abstract = {We prove that the local eigenvalue statistics of real symmetric Wigner-type matrices near the cusp points of the eigenvalue density are universal. Together with the companion paper [arXiv:1809.03971], which proves the same result for the complex Hermitian symmetry class, this completes the last remaining case of the Wigner-Dyson-Mehta universality conjecture after bulk and edge universalities have been established in the last years. We extend the recent Dyson Brownian motion analysis at the edge [arXiv:1712.03881] to the cusp regime using the optimal local law from [arXiv:1809.03971] and the accurate local shape analysis of the density from [arXiv:1506.05095, arXiv:1804.07752]. We also present a PDE-based method to improve the estimate on eigenvalue rigidity via the maximum principle of the heat flow related to the Dyson Brownian motion.}, author = {Cipolloni, Giorgio and Erdös, László and Krüger, Torben H and Schröder, Dominik J}, issn = {2578-5885}, journal = {Pure and Applied Analysis }, number = {4}, pages = {615–707}, publisher = {MSP}, title = {{Cusp universality for random matrices, II: The real symmetric case}}, doi = {10.2140/paa.2019.1.615}, volume = {1}, year = {2019}, } @article{6900, abstract = {Across diverse biological systems—ranging from neural networks to intracellular signaling and genetic regulatory networks—the information about changes in the environment is frequently encoded in the full temporal dynamics of the network nodes. A pressing data-analysis challenge has thus been to efficiently estimate the amount of information that these dynamics convey from experimental data. Here we develop and evaluate decoding-based estimation methods to lower bound the mutual information about a finite set of inputs, encoded in single-cell high-dimensional time series data. For biological reaction networks governed by the chemical Master equation, we derive model-based information approximations and analytical upper bounds, against which we benchmark our proposed model-free decoding estimators. In contrast to the frequently-used k-nearest-neighbor estimator, decoding-based estimators robustly extract a large fraction of the available information from high-dimensional trajectories with a realistic number of data samples. We apply these estimators to previously published data on Erk and Ca2+ signaling in mammalian cells and to yeast stress-response, and find that substantial amount of information about environmental state can be encoded by non-trivial response statistics even in stationary signals. We argue that these single-cell, decoding-based information estimates, rather than the commonly-used tests for significant differences between selected population response statistics, provide a proper and unbiased measure for the performance of biological signaling networks.}, author = {Cepeda Humerez, Sarah A and Ruess, Jakob and Tkačik, Gašper}, issn = {15537358}, journal = {PLoS computational biology}, number = {9}, pages = {e1007290}, publisher = {Public Library of Science}, title = {{Estimating information in time-varying signals}}, doi = {10.1371/journal.pcbi.1007290}, volume = {15}, year = {2019}, } @article{6377, abstract = {Clathrin-mediated endocytosis (CME) is a highly conserved and essential cellular process in eukaryotic cells, but its dynamic and vital nature makes it challenging to study using classical genetics tools. In contrast, although small molecules can acutely and reversibly perturb CME, the few chemical CME inhibitors that have been applied to plants are either ineffective or show undesirable side effects. Here, we identify the previously described endosidin9 (ES9) as an inhibitor of clathrin heavy chain (CHC) function in both Arabidopsis and human cells through affinity-based target isolation, in vitro binding studies and X-ray crystallography. Moreover, we present a chemically improved ES9 analog, ES9-17, which lacks the undesirable side effects of ES9 while retaining the ability to target CHC. ES9 and ES9-17 have expanded the chemical toolbox used to probe CHC function, and present chemical scaffolds for further design of more specific and potent CHC inhibitors across different systems.}, author = {Dejonghe, Wim and Sharma, Isha and Denoo, Bram and De Munck, Steven and Lu, Qing and Mishev, Kiril and Bulut, Haydar and Mylle, Evelien and De Rycke, Riet and Vasileva, Mina K and Savatin, Daniel V. and Nerinckx, Wim and Staes, An and Drozdzecki, Andrzej and Audenaert, Dominique and Yperman, Klaas and Madder, Annemieke and Friml, Jiří and Van Damme, Daniël and Gevaert, Kris and Haucke, Volker and Savvides, Savvas N. and Winne, Johan and Russinova, Eugenia}, issn = {15524469}, journal = {Nature Chemical Biology}, number = {6}, pages = {641–649}, publisher = {Springer Nature}, title = {{Disruption of endocytosis through chemical inhibition of clathrin heavy chain function}}, doi = {10.1038/s41589-019-0262-1}, volume = {15}, year = {2019}, } @phdthesis{7186, abstract = {Tissue morphogenesis in developmental or physiological processes is regulated by molecular and mechanical signals. While the molecular signaling cascades are increasingly well described, the mechanical signals affecting tissue shape changes have only recently been studied in greater detail. To gain more insight into the mechanochemical and biophysical basis of an epithelial spreading process (epiboly) in early zebrafish development, we studied cell-cell junction formation and actomyosin network dynamics at the boundary between surface layer epithelial cells (EVL) and the yolk syncytial layer (YSL). During zebrafish epiboly, the cell mass sitting on top of the yolk cell spreads to engulf the yolk cell by the end of gastrulation. It has been previously shown that an actomyosin ring residing within the YSL pulls on the EVL tissue through a cable-constriction and a flow-friction motor, thereby dragging the tissue vegetal wards. Pulling forces are likely transmitted from the YSL actomyosin ring to EVL cells; however, the nature and formation of the junctional structure mediating this process has not been well described so far. Therefore, our main aim was to determine the nature, dynamics and potential function of the EVL-YSL junction during this epithelial tissue spreading. Specifically, we show that the EVL-YSL junction is a mechanosensitive structure, predominantly made of tight junction (TJ) proteins. The process of TJ mechanosensation depends on the retrograde flow of non-junctional, phase-separated Zonula Occludens-1 (ZO-1) protein clusters towards the EVL-YSL boundary. Interestingly, we could demonstrate that ZO-1 is present in a non-junctional pool on the surface of the yolk cell, and ZO-1 undergoes a phase separation process that likely renders the protein responsive to flows. These flows are directed towards the junction and mediate proper tension-dependent recruitment of ZO-1. Upon reaching the EVL-YSL junction ZO-1 gets incorporated into the junctional pool mediated through its direct actin-binding domain. When the non-junctional pool and/or ZO-1 direct actin binding is absent, TJs fail in their proper mechanosensitive responses resulting in slower tissue spreading. We could further demonstrate that depletion of ZO proteins within the YSL results in diminished actomyosin ring formation. This suggests that a mechanochemical feedback loop is at work during zebrafish epiboly: ZO proteins help in proper actomyosin ring formation and actomyosin contractility and flows positively influence ZO-1 junctional recruitment. Finally, such a mesoscale polarization process mediated through the flow of phase-separated protein clusters might have implications for other processes such as immunological synapse formation, C. elegans zygote polarization and wound healing.}, author = {Schwayer, Cornelia}, issn = {2663-337X}, pages = {107}, publisher = {Institute of Science and Technology Austria}, title = {{Mechanosensation of tight junctions depends on ZO-1 phase separation and flow}}, doi = {10.15479/AT:ISTA:7186}, year = {2019}, } @phdthesis{6681, abstract = {The first part of the thesis considers the computational aspects of the homotopy groups πd(X) of a topological space X. It is well known that there is no algorithm to decide whether the fundamental group π1(X) of a given finite simplicial complex X is trivial. On the other hand, there are several algorithms that, given a finite simplicial complex X that is simply connected (i.e., with π1(X) trivial), compute the higher homotopy group πd(X) for any given d ≥ 2. However, these algorithms come with a caveat: They compute the isomorphism type of πd(X), d ≥ 2 as an abstract finitely generated abelian group given by generators and relations, but they work with very implicit representations of the elements of πd(X). We present an algorithm that, given a simply connected space X, computes πd(X) and represents its elements as simplicial maps from suitable triangulations of the d-sphere Sd to X. For fixed d, the algorithm runs in time exponential in size(X), the number of simplices of X. Moreover, we prove that this is optimal: For every fixed d ≥ 2, we construct a family of simply connected spaces X such that for any simplicial map representing a generator of πd(X), the size of the triangulation of S d on which the map is defined, is exponential in size(X). In the second part of the thesis, we prove that the following question is algorithmically undecidable for d < ⌊3(k+1)/2⌋, k ≥ 5 and (k, d) ̸= (5, 7), which covers essentially everything outside the meta-stable range: Given a finite simplicial complex K of dimension k, decide whether there exists a piecewise-linear (i.e., linear on an arbitrarily fine subdivision of K) embedding f : K ↪→ Rd of K into a d-dimensional Euclidean space.}, author = {Zhechev, Stephan Y}, issn = {2663-337X}, pages = {104}, publisher = {Institute of Science and Technology Austria}, title = {{Algorithmic aspects of homotopy theory and embeddability}}, doi = {10.15479/AT:ISTA:6681}, year = {2019}, } @unpublished{8182, abstract = {Suppose that $n\neq p^k$ and $n\neq 2p^k$ for all $k$ and all primes $p$. We prove that for any Hausdorff compactum $X$ with a free action of the symmetric group $\mathfrak S_n$ there exists an $\mathfrak S_n$-equivariant map $X \to {\mathbb R}^n$ whose image avoids the diagonal $\{(x,x\dots,x)\in {\mathbb R}^n|x\in {\mathbb R}\}$. Previously, the special cases of this statement for certain $X$ were usually proved using the equivartiant obstruction theory. Such calculations are difficult and may become infeasible past the first (primary) obstruction. We take a different approach which allows us to prove the vanishing of all obstructions simultaneously. The essential step in the proof is classifying the possible degrees of $\mathfrak S_n$-equivariant maps from the boundary $\partial\Delta^{n-1}$ of $(n-1)$-simplex to itself. Existence of equivariant maps between spaces is important for many questions arising from discrete mathematics and geometry, such as Kneser's conjecture, the Square Peg conjecture, the Splitting Necklace problem, and the Topological Tverberg conjecture, etc. We demonstrate the utility of our result applying it to one such question, a specific instance of envy-free division problem.}, author = {Avvakumov, Sergey and Kudrya, Sergey}, booktitle = {arXiv}, publisher = {arXiv}, title = {{Vanishing of all equivariant obstructions and the mapping degree}}, year = {2019}, } @unpublished{8185, abstract = {In this paper we study envy-free division problems. The classical approach to some of such problems, used by David Gale, reduces to considering continuous maps of a simplex to itself and finding sufficient conditions when this map hits the center of the simplex. The mere continuity is not sufficient for such a conclusion, the usual assumption (for example, in the Knaster--Kuratowski--Mazurkiewicz and the Gale theorem) is a certain boundary condition. We follow Erel Segal-Halevi, Fr\'ed\'eric Meunier, and Shira Zerbib, and replace the boundary condition by another assumption, which has the economic meaning of possibility for a player to prefer an empty part in the segment partition problem. We solve the problem positively when $n$, the number of players that divide the segment, is a prime power, and we provide counterexamples for every $n$ which is not a prime power. We also provide counterexamples relevant to a wider class of fair or envy-free partition problems when $n$ is odd and not a prime power.}, author = {Avvakumov, Sergey and Karasev, Roman}, booktitle = {arXiv}, title = {{Envy-free division using mapping degree}}, doi = {10.48550/arXiv.1907.11183}, year = {2019}, } @unpublished{7524, abstract = {We prove a lower bound for the free energy (per unit volume) of the two-dimensional Bose gas in the thermodynamic limit. We show that the free energy at density $\rho$ and inverse temperature $\beta$ differs from the one of the non-interacting system by the correction term $4 \pi \rho^2 |\ln a^2 \rho|^{-1} (2 - [1 - \beta_{\mathrm{c}}/\beta]_+^2)$. Here $a$ is the scattering length of the interaction potential, $[\cdot]_+ = \max\{ 0, \cdot \}$ and $\beta_{\mathrm{c}}$ is the inverse Berezinskii--Kosterlitz--Thouless critical temperature for superfluidity. The result is valid in the dilute limit $a^2\rho \ll 1$ and if $\beta \rho \gtrsim 1$.}, author = {Deuchert, Andreas and Mayer, Simon and Seiringer, Robert}, booktitle = {arXiv:1910.03372}, pages = {61}, publisher = {ArXiv}, title = {{The free energy of the two-dimensional dilute Bose gas. I. Lower bound}}, year = {2019}, } @article{6608, abstract = {We use the canonical bases produced by the tri-partition algorithm in (Edelsbrunner and Ölsböck, 2018) to open and close holes in a polyhedral complex, K. In a concrete application, we consider the Delaunay mosaic of a finite set, we let K be an Alpha complex, and we use the persistence diagram of the distance function to guide the hole opening and closing operations. The dependences between the holes define a partial order on the cells in K that characterizes what can and what cannot be constructed using the operations. The relations in this partial order reveal structural information about the underlying filtration of complexes beyond what is expressed by the persistence diagram.}, author = {Edelsbrunner, Herbert and Ölsböck, Katharina}, journal = {Computer Aided Geometric Design}, pages = {1--15}, publisher = {Elsevier}, title = {{Holes and dependences in an ordered complex}}, doi = {10.1016/j.cagd.2019.06.003}, volume = {73}, year = {2019}, } @inproceedings{6677, abstract = {The Fiat-Shamir heuristic transforms a public-coin interactive proof into a non-interactive argument, by replacing the verifier with a cryptographic hash function that is applied to the protocol’s transcript. Constructing hash functions for which this transformation is sound is a central and long-standing open question in cryptography. We show that solving the END−OF−METERED−LINE problem is no easier than breaking the soundness of the Fiat-Shamir transformation when applied to the sumcheck protocol. In particular, if the transformed protocol is sound, then any hard problem in #P gives rise to a hard distribution in the class CLS, which is contained in PPAD. Our result opens up the possibility of sampling moderately-sized games for which it is hard to find a Nash equilibrium, by reducing the inversion of appropriately chosen one-way functions to #SAT. Our main technical contribution is a stateful incrementally verifiable procedure that, given a SAT instance over n variables, counts the number of satisfying assignments. This is accomplished via an exponential sequence of small steps, each computable in time poly(n). Incremental verifiability means that each intermediate state includes a sumcheck-based proof of its correctness, and the proof can be updated and verified in time poly(n).}, author = {Choudhuri, Arka Rai and Hubáček, Pavel and Kamath Hosdurg, Chethan and Pietrzak, Krzysztof Z and Rosen, Alon and Rothblum, Guy N.}, booktitle = {Proceedings of the 51st Annual ACM SIGACT Symposium on Theory of Computing - STOC 2019}, isbn = {9781450367059}, location = {Phoenix, AZ, United States}, pages = {1103--1114}, publisher = {ACM Press}, title = {{Finding a Nash equilibrium is no easier than breaking Fiat-Shamir}}, doi = {10.1145/3313276.3316400}, 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{5886, abstract = {Problems involving quantum impurities, in which one or a few particles are interacting with a macroscopic environment, represent a pervasive paradigm, spanning across atomic, molecular, and condensed-matter physics. In this paper we introduce new variational approaches to quantum impurities and apply them to the Fröhlich polaron–a quasiparticle formed out of an electron (or other point-like impurity) in a polar medium, and to the angulon–a quasiparticle formed out of a rotating molecule in a bosonic bath. We benchmark these approaches against established theories, evaluating their accuracy as a function of the impurity-bath coupling.}, author = {Li, Xiang and Bighin, Giacomo and Yakaboylu, Enderalp and Lemeshko, Mikhail}, issn = {00268976}, journal = {Molecular Physics}, publisher = {Taylor and Francis}, title = {{Variational approaches to quantum impurities: from the Fröhlich polaron to the angulon}}, doi = {10.1080/00268976.2019.1567852}, year = {2019}, } @inproceedings{6556, abstract = {Motivated by fixed-parameter tractable (FPT) problems in computational topology, we consider the treewidth tw(M) of a compact, connected 3-manifold M, defined to be the minimum treewidth of the face pairing graph of any triangulation T of M. In this setting the relationship between the topology of a 3-manifold and its treewidth is of particular interest. First, as a corollary of work of Jaco and Rubinstein, we prove that for any closed, orientable 3-manifold M the treewidth tw(M) is at most 4g(M)-2, where g(M) denotes Heegaard genus of M. In combination with our earlier work with Wagner, this yields that for non-Haken manifolds the Heegaard genus and the treewidth are within a constant factor. Second, we characterize all 3-manifolds of treewidth one: These are precisely the lens spaces and a single other Seifert fibered space. Furthermore, we show that all remaining orientable Seifert fibered spaces over the 2-sphere or a non-orientable surface have treewidth two. In particular, for every spherical 3-manifold we exhibit a triangulation of treewidth at most two. Our results further validate the parameter of treewidth (and other related parameters such as cutwidth or congestion) to be useful for topological computing, and also shed more light on the scope of existing FPT-algorithms in the field.}, author = {Huszár, Kristóf and Spreer, Jonathan}, booktitle = {35th International Symposium on Computational Geometry}, isbn = {978-3-95977-104-7}, issn = {1868-8969}, keywords = {computational 3-manifold topology, fixed-parameter tractability, layered triangulations, structural graph theory, treewidth, cutwidth, Heegaard genus}, location = {Portland, Oregon, United States}, pages = {44:1--44:20}, publisher = {Schloss Dagstuhl - Leibniz-Zentrum für Informatik}, title = {{3-manifold triangulations with small treewidth}}, doi = {10.4230/LIPIcs.SoCG.2019.44}, volume = {129}, year = {2019}, } @article{7093, abstract = {In graph theory, as well as in 3-manifold topology, there exist several width-type parameters to describe how "simple" or "thin" a given graph or 3-manifold is. These parameters, such as pathwidth or treewidth for graphs, or the concept of thin position for 3-manifolds, play an important role when studying algorithmic problems; in particular, there is a variety of problems in computational 3-manifold topology - some of them known to be computationally hard in general - that become solvable in polynomial time as soon as the dual graph of the input triangulation has bounded treewidth. In view of these algorithmic results, it is natural to ask whether every 3-manifold admits a triangulation of bounded treewidth. We show that this is not the case, i.e., that there exists an infinite family of closed 3-manifolds not admitting triangulations of bounded pathwidth or treewidth (the latter implies the former, but we present two separate proofs). We derive these results from work of Agol, of Scharlemann and Thompson, and of Scharlemann, Schultens and Saito by exhibiting explicit connections between the topology of a 3-manifold M on the one hand and width-type parameters of the dual graphs of triangulations of M on the other hand, answering a question that had been raised repeatedly by researchers in computational 3-manifold topology. In particular, we show that if a closed, orientable, irreducible, non-Haken 3-manifold M has a triangulation of treewidth (resp. pathwidth) k then the Heegaard genus of M is at most 18(k+1) (resp. 4(3k+1)).}, author = {Huszár, Kristóf and Spreer, Jonathan and Wagner, Uli}, issn = {1920-180X}, journal = {Journal of Computational Geometry}, number = {2}, pages = {70–98}, publisher = {Computational Geometry Laborartoy}, title = {{On the treewidth of triangulated 3-manifolds}}, doi = {10.20382/JOGC.V10I2A5}, volume = {10}, year = {2019}, } @article{7197, abstract = {During bacterial cell division, the tubulin-homolog FtsZ forms a ring-like structure at the center of the cell. This Z-ring not only organizes the division machinery, but treadmilling of FtsZ filaments was also found to play a key role in distributing proteins at the division site. What regulates the architecture, dynamics and stability of the Z-ring is currently unknown, but FtsZ-associated proteins are known to play an important role. Here, using an in vitro reconstitution approach, we studied how the well-conserved protein ZapA affects FtsZ treadmilling and filament organization into large-scale patterns. Using high-resolution fluorescence microscopy and quantitative image analysis, we found that ZapA cooperatively increases the spatial order of the filament network, but binds only transiently to FtsZ filaments and has no effect on filament length and treadmilling velocity. Together, our data provides a model for how FtsZ-associated proteins can increase the precision and stability of the bacterial cell division machinery in a switch-like manner.}, author = {Dos Santos Caldas, Paulo R and Lopez Pelegrin, Maria D and Pearce, Daniel J. G. and Budanur, Nazmi B and Brugués, Jan and Loose, Martin}, issn = {2041-1723}, journal = {Nature Communications}, publisher = {Springer Nature}, title = {{Cooperative ordering of treadmilling filaments in cytoskeletal networks of FtsZ and its crosslinker ZapA}}, doi = {10.1038/s41467-019-13702-4}, volume = {10}, year = {2019}, } @article{7210, abstract = {The rate of biological evolution depends on the fixation probability and on the fixation time of new mutants. Intensive research has focused on identifying population structures that augment the fixation probability of advantageous mutants. But these amplifiers of natural selection typically increase fixation time. Here we study population structures that achieve a tradeoff between fixation probability and time. First, we show that no amplifiers can have an asymptotically lower absorption time than the well-mixed population. Then we design population structures that substantially augment the fixation probability with just a minor increase in fixation time. Finally, we show that those structures enable higher effective rate of evolution than the well-mixed population provided that the rate of generating advantageous mutants is relatively low. Our work sheds light on how population structure affects the rate of evolution. Moreover, our structures could be useful for lab-based, medical, or industrial applications of evolutionary optimization.}, author = {Tkadlec, Josef and Pavlogiannis, Andreas and Chatterjee, Krishnendu and Nowak, Martin A.}, issn = {2399-3642}, journal = {Communications Biology}, publisher = {Springer Nature}, title = {{Population structure determines the tradeoff between fixation probability and fixation time}}, doi = {10.1038/s42003-019-0373-y}, volume = {2}, year = {2019}, } @inproceedings{10190, abstract = {The verification of concurrent programs remains an open challenge, as thread interaction has to be accounted for, which leads to state-space explosion. Stateless model checking battles this problem by exploring traces rather than states of the program. As there are exponentially many traces, dynamic partial-order reduction (DPOR) techniques are used to partition the trace space into equivalence classes, and explore a few representatives from each class. The standard equivalence that underlies most DPOR techniques is the happens-before equivalence, however recent works have spawned a vivid interest towards coarser equivalences. The efficiency of such approaches is a product of two parameters: (i) the size of the partitioning induced by the equivalence, and (ii) the time spent by the exploration algorithm in each class of the partitioning. In this work, we present a new equivalence, called value-happens-before and show that it has two appealing features. First, value-happens-before is always at least as coarse as the happens-before equivalence, and can be even exponentially coarser. Second, the value-happens-before partitioning is efficiently explorable when the number of threads is bounded. We present an algorithm called value-centric DPOR (VCDPOR), which explores the underlying partitioning using polynomial time per class. Finally, we perform an experimental evaluation of VCDPOR on various benchmarks, and compare it against other state-of-the-art approaches. Our results show that value-happens-before typically induces a significant reduction in the size of the underlying partitioning, which leads to a considerable reduction in the running time for exploring the whole partitioning.}, author = {Chatterjee, Krishnendu and Pavlogiannis, Andreas and Toman, Viktor}, booktitle = {Proceedings of the 34th ACM International Conference on Object-Oriented Programming, Systems, Languages, and Applications}, issn = {2475-1421}, keywords = {safety, risk, reliability and quality, software}, location = {Athens, Greece}, publisher = {ACM}, title = {{Value-centric dynamic partial order reduction}}, doi = {10.1145/3360550}, volume = {3}, year = {2019}, } @inproceedings{6673, abstract = {Several classic problems in graph processing and computational geometry are solved via incremental algorithms, which split computation into a series of small tasks acting on shared state, which gets updated progressively. While the sequential variant of such algorithms usually specifies a fixed (but sometimes random) order in which the tasks should be performed, a standard approach to parallelizing such algorithms is to relax this constraint to allow for out-of-order parallel execution. This is the case for parallel implementations of Dijkstra's single-source shortest-paths (SSSP) algorithm, and for parallel Delaunay mesh triangulation. While many software frameworks parallelize incremental computation in this way, it is still not well understood whether this relaxed ordering approach can still provide any complexity guarantees. In this paper, we address this problem, and analyze the efficiency guarantees provided by a range of incremental algorithms when parallelized via relaxed schedulers. We show that, for algorithms such as Delaunay mesh triangulation and sorting by insertion, schedulers with a maximum relaxation factor of k in terms of the maximum priority inversion allowed will introduce a maximum amount of wasted work of O(łog n poly(k)), where n is the number of tasks to be executed. For SSSP, we show that the additional work is O(poly(k), dmax / wmin), where dmax is the maximum distance between two nodes, and wmin is the minimum such distance. In practical settings where n >> k, this suggests that the overheads of relaxation will be outweighed by the improved scalability of the relaxed scheduler. On the negative side, we provide lower bounds showing that certain algorithms will inherently incur a non-trivial amount of wasted work due to scheduler relaxation, even for relatively benign relaxed schedulers.}, author = {Alistarh, Dan-Adrian and Nadiradze, Giorgi and Koval, Nikita}, booktitle = {31st ACM Symposium on Parallelism in Algorithms and Architectures}, isbn = {9781450361842}, location = {Phoenix, AZ, United States}, pages = {145--154}, publisher = {ACM Press}, title = {{Efficiency guarantees for parallel incremental algorithms under relaxed schedulers}}, doi = {10.1145/3323165.3323201}, year = {2019}, } @article{7398, abstract = {Transporters of the solute carrier 6 (SLC6) family translocate their cognate substrate together with Na+ and Cl−. Detailed kinetic models exist for the transporters of GABA (GAT1/SLC6A1) and the monoamines dopamine (DAT/SLC6A3) and serotonin (SERT/SLC6A4). Here, we posited that the transport cycle of individual SLC6 transporters reflects the physiological requirements they operate under. We tested this hypothesis by analyzing the transport cycle of glycine transporter 1 (GlyT1/SLC6A9) and glycine transporter 2 (GlyT2/SLC6A5). GlyT2 is the only SLC6 family member known to translocate glycine, Na+, and Cl− in a 1:3:1 stoichiometry. We analyzed partial reactions in real time by electrophysiological recordings. Contrary to monoamine transporters, both GlyTs were found to have a high transport capacity driven by rapid return of the empty transporter after release of Cl− on the intracellular side. Rapid cycling of both GlyTs was further supported by highly cooperative binding of cosubstrate ions and substrate such that their forward transport mode was maintained even under conditions of elevated intracellular Na+ or Cl−. The most important differences in the transport cycle of GlyT1 and GlyT2 arose from the kinetics of charge movement and the resulting voltage-dependent rate-limiting reactions: the kinetics of GlyT1 were governed by transition of the substrate-bound transporter from outward- to inward-facing conformations, whereas the kinetics of GlyT2 were governed by Na+ binding (or a related conformational change). Kinetic modeling showed that the kinetics of GlyT1 are ideally suited for supplying the extracellular glycine levels required for NMDA receptor activation.}, author = {Erdem, Fatma Asli and Ilic, Marija and Koppensteiner, Peter and Gołacki, Jakub and Lubec, Gert and Freissmuth, Michael and Sandtner, Walter}, issn = {1540-7748}, journal = {The Journal of General Physiology}, number = {8}, pages = {1035--1050}, publisher = {Rockefeller University Press}, title = {{A comparison of the transport kinetics of glycine transporter 1 and glycine transporter 2}}, doi = {10.1085/jgp.201912318}, volume = {151}, year = {2019}, } @article{7395, abstract = {The mitochondrial electron transport chain complexes are organized into supercomplexes (SCs) of defined stoichiometry, which have been proposed to regulate electron flux via substrate channeling. We demonstrate that CoQ trapping in the isolated SC I+III2 limits complex (C)I turnover, arguing against channeling. The SC structure, resolved at up to 3.8 Å in four distinct states, suggests that CoQ oxidation may be rate limiting because of unequal access of CoQ to the active sites of CIII2. CI shows a transition between “closed” and “open” conformations, accompanied by the striking rotation of a key transmembrane helix. Furthermore, the state of CI affects the conformational flexibility within CIII2, demonstrating crosstalk between the enzymes. CoQ was identified at only three of the four binding sites in CIII2, suggesting that interaction with CI disrupts CIII2 symmetry in a functionally relevant manner. Together, these observations indicate a more nuanced functional role for the SCs.}, author = {Letts, James A and Fiedorczuk, Karol and Degliesposti, Gianluca and Skehel, Mark and Sazanov, Leonid A}, issn = {1097-2765}, journal = {Molecular Cell}, number = {6}, pages = {1131--1146.e6}, publisher = {Cell Press}, title = {{Structures of respiratory supercomplex I+III2 reveal functional and conformational crosstalk}}, doi = {10.1016/j.molcel.2019.07.022}, volume = {75}, year = {2019}, } @article{7405, abstract = {Biophysical modeling of neuronal networks helps to integrate and interpret rapidly growing and disparate experimental datasets at multiple scales. The NetPyNE tool (www.netpyne.org) provides both programmatic and graphical interfaces to develop data-driven multiscale network models in NEURON. NetPyNE clearly separates model parameters from implementation code. Users provide specifications at a high level via a standardized declarative language, for example connectivity rules, to create millions of cell-to-cell connections. NetPyNE then enables users to generate the NEURON network, run efficiently parallelized simulations, optimize and explore network parameters through automated batch runs, and use built-in functions for visualization and analysis – connectivity matrices, voltage traces, spike raster plots, local field potentials, and information theoretic measures. NetPyNE also facilitates model sharing by exporting and importing standardized formats (NeuroML and SONATA). NetPyNE is already being used to teach computational neuroscience students and by modelers to investigate brain regions and phenomena.}, author = {Dura-Bernal, Salvador and Suter, Benjamin and Gleeson, Padraig and Cantarelli, Matteo and Quintana, Adrian and Rodriguez, Facundo and Kedziora, David J and Chadderdon, George L and Kerr, Cliff C and Neymotin, Samuel A and McDougal, Robert A and Hines, Michael and Shepherd, Gordon MG and Lytton, William W}, issn = {2050-084X}, journal = {eLife}, publisher = {eLife Sciences Publications}, title = {{NetPyNE, a tool for data-driven multiscale modeling of brain circuits}}, doi = {10.7554/elife.44494}, volume = {8}, year = {2019}, } @article{7400, abstract = {Suppressed recombination allows divergence between homologous sex chromosomes and the functionality of their genes. Here, we reveal patterns of the earliest stages of sex-chromosome evolution in the diploid dioecious herb Mercurialis annua on the basis of cytological analysis, de novo genome assembly and annotation, genetic mapping, exome resequencing of natural populations, and transcriptome analysis. The genome assembly contained 34,105 expressed genes, of which 10,076 were assigned to linkage groups. Genetic mapping and exome resequencing of individuals across the species range both identified the largest linkage group, LG1, as the sex chromosome. Although the sex chromosomes of M. annua are karyotypically homomorphic, we estimate that about one-third of the Y chromosome, containing 568 transcripts and spanning 22.3 cM in the corresponding female map, has ceased recombining. Nevertheless, we found limited evidence for Y-chromosome degeneration in terms of gene loss and pseudogenization, and most X- and Y-linked genes appear to have diverged in the period subsequent to speciation between M. annua and its sister species M. huetii, which shares the same sex-determining region. Taken together, our results suggest that the M. annua Y chromosome has at least two evolutionary strata: a small old stratum shared with M. huetii, and a more recent larger stratum that is probably unique to M. annua and that stopped recombining ∼1 MYA. Patterns of gene expression within the nonrecombining region are consistent with the idea that sexually antagonistic selection may have played a role in favoring suppressed recombination.}, author = {Veltsos, Paris and Ridout, Kate E. and Toups, Melissa A and González-Martínez, Santiago C. and Muyle, Aline and Emery, Olivier and Rastas, Pasi and Hudzieczek, Vojtech and Hobza, Roman and Vyskot, Boris and Marais, Gabriel A. B. and Filatov, Dmitry A. and Pannell, John R.}, issn = {1943-2631}, journal = {Genetics}, number = {3}, pages = {815--835}, publisher = {Genetics Society of America}, title = {{Early sex-chromosome evolution in the diploid dioecious plant Mercurialis annua}}, doi = {10.1534/genetics.119.302045}, volume = {212}, year = {2019}, } @article{7404, abstract = {The formation of neuronal dendrite branches is fundamental for the wiring and function of the nervous system. Indeed, dendrite branching enhances the coverage of the neuron's receptive field and modulates the initial processing of incoming stimuli. Complex dendrite patterns are achieved in vivo through a dynamic process of de novo branch formation, branch extension and retraction. The first step towards branch formation is the generation of a dynamic filopodium-like branchlet. The mechanisms underlying the initiation of dendrite branchlets are therefore crucial to the shaping of dendrites. Through in vivo time-lapse imaging of the subcellular localization of actin during the process of branching of Drosophila larva sensory neurons, combined with genetic analysis and electron tomography, we have identified the Actin-related protein (Arp) 2/3 complex as the major actin nucleator involved in the initiation of dendrite branchlet formation, under the control of the activator WAVE and of the small GTPase Rac1. Transient recruitment of an Arp2/3 component marks the site of branchlet initiation in vivo. These data position the activation of Arp2/3 as an early hub for the initiation of branchlet formation.}, author = {Stürner, Tomke and Tatarnikova, Anastasia and Müller, Jan and Schaffran, Barbara and Cuntz, Hermann and Zhang, Yun and Nemethova, Maria and Bogdan, Sven and Small, Vic and Tavosanis, Gaia}, issn = {1477-9129}, journal = {Development}, number = {7}, publisher = {The Company of Biologists}, title = {{Transient localization of the Arp2/3 complex initiates neuronal dendrite branching in vivo}}, doi = {10.1242/dev.171397}, volume = {146}, year = {2019}, } @inproceedings{7402, abstract = {Graph planning gives rise to fundamental algorithmic questions such as shortest path, traveling salesman problem, etc. A classical problem in discrete planning is to consider a weighted graph and construct a path that maximizes the sum of weights for a given time horizon T. However, in many scenarios, the time horizon is not fixed, but the stopping time is chosen according to some distribution such that the expected stopping time is T. If the stopping time distribution is not known, then to ensure robustness, the distribution is chosen by an adversary, to represent the worst-case scenario. A stationary plan for every vertex always chooses the same outgoing edge. For fixed horizon or fixed stopping-time distribution, stationary plans are not sufficient for optimality. Quite surprisingly we show that when an adversary chooses the stopping-time distribution with expected stopping time T, then stationary plans are sufficient. While computing optimal stationary plans for fixed horizon is NP-complete, we show that computing optimal stationary plans under adversarial stopping-time distribution can be achieved in polynomial time. Consequently, our polynomial-time algorithm for adversarial stopping time also computes an optimal plan among all possible plans.}, author = {Chatterjee, Krishnendu and Doyen, Laurent}, booktitle = {34th Annual ACM/IEEE Symposium on Logic in Computer Science}, isbn = {9781728136080}, location = {Vancouver, BC, Canada}, pages = {1--13}, publisher = {IEEE}, title = {{Graph planning with expected finite horizon}}, doi = {10.1109/lics.2019.8785706}, year = {2019}, } @article{7451, abstract = {We prove that the observable telegraph signal accompanying the bistability in the photon-blockade-breakdown regime of the driven and lossy Jaynes–Cummings model is the finite-size precursor of what in the thermodynamic limit is a genuine first-order phase transition. We construct a finite-size scaling of the system parameters to a well-defined thermodynamic limit, in which the system remains the same microscopic system, but the telegraph signal becomes macroscopic both in its timescale and intensity. The existence of such a finite-size scaling completes and justifies the classification of the photon-blockade-breakdown effect as a first-order dissipative quantum phase transition.}, author = {Vukics, A. and Dombi, A. and Fink, Johannes M and Domokos, P.}, issn = {2521-327X}, journal = {Quantum}, publisher = {Verein zur Förderung des Open Access Publizierens in den Quantenwissenschaften}, title = {{Finite-size scaling of the photon-blockade breakdown dissipative quantum phase transition}}, doi = {10.22331/q-2019-06-03-150}, volume = {3}, year = {2019}, } @inproceedings{7468, abstract = {We present a new proximal bundle method for Maximum-A-Posteriori (MAP) inference in structured energy minimization problems. The method optimizes a Lagrangean relaxation of the original energy minimization problem using a multi plane block-coordinate Frank-Wolfe method that takes advantage of the specific structure of the Lagrangean decomposition. We show empirically that our method outperforms state-of-the-art Lagrangean decomposition based algorithms on some challenging Markov Random Field, multi-label discrete tomography and graph matching problems.}, author = {Swoboda, Paul and Kolmogorov, Vladimir}, booktitle = {Proceedings of the IEEE Computer Society Conference on Computer Vision and Pattern Recognition}, isbn = {9781728132938}, issn = {10636919}, location = {Long Beach, CA, United States}, publisher = {IEEE}, title = {{Map inference via block-coordinate Frank-Wolfe algorithm}}, doi = {10.1109/CVPR.2019.01140}, volume = {2019-June}, year = {2019}, } @article{7415, author = {Morandell, Jasmin and Nicolas, Armel and Schwarz, Lena A and Novarino, Gaia}, issn = {0924-977X}, journal = {European Neuropsychopharmacology}, number = {Supplement 6}, pages = {S11--S12}, publisher = {Elsevier}, title = {{S.16.05 Illuminating the role of the e3 ubiquitin ligase cullin3 in brain development and autism}}, doi = {10.1016/j.euroneuro.2019.09.040}, volume = {29}, year = {2019}, } @article{7414, author = {Knaus, Lisa and Tarlungeanu, Dora-Clara and Novarino, Gaia}, issn = {0924-977X}, journal = {European Neuropsychopharmacology}, number = {Supplement 6}, pages = {S11}, publisher = {Elsevier}, title = {{S.16.03 A homozygous missense mutation in SLC7A5 leads to autism spectrum disorder and microcephaly}}, doi = {10.1016/j.euroneuro.2019.09.039}, volume = {29}, year = {2019}, } @article{7394, author = {Benková, Eva and Dagdas, Yasin}, issn = {1369-5266}, journal = {Current Opinion in Plant Biology}, number = {12}, pages = {A1--A2}, publisher = {Elsevier}, title = {{Editorial overview: Cell biology in the era of omics?}}, doi = {10.1016/j.pbi.2019.11.002}, volume = {52}, year = {2019}, } @inproceedings{7479, abstract = {Multi-exit architectures, in which a stack of processing layers is interleaved with early output layers, allow the processing of a test example to stop early and thus save computation time and/or energy. In this work, we propose a new training procedure for multi-exit architectures based on the principle of knowledge distillation. The method encourage searly exits to mimic later, more accurate exits, by matching their output probabilities. Experiments on CIFAR100 and ImageNet show that distillation-based training significantly improves the accuracy of early exits while maintaining state-of-the-art accuracy for late ones. The method is particularly beneficial when training data is limited and it allows a straightforward extension to semi-supervised learning,i.e. making use of unlabeled data at training time. Moreover, it takes only afew lines to implement and incurs almost no computational overhead at training time, and none at all at test time.}, author = {Bui Thi Mai, Phuong and Lampert, Christoph}, booktitle = {IEEE International Conference on Computer Vision}, isbn = {9781728148038}, issn = {15505499}, location = {Seoul, Korea}, pages = {1355--1364}, publisher = {IEEE}, title = {{Distillation-based training for multi-exit architectures}}, doi = {10.1109/ICCV.2019.00144}, volume = {2019-October}, year = {2019}, }