TY - JOUR AB - PIN-FORMED (PIN) transporters mediate directional, intercellular movement of the phytohormone auxin in land plants. To elucidate the evolutionary origins of this developmentally crucial mechanism, we analysed the single PIN homologue of a simple green alga Klebsormidium flaccidum. KfPIN functions as a plasma membrane-localized auxin exporter in land plants and heterologous models. While its role in algae remains unclear, PIN-driven auxin export is probably an ancient and conserved trait within streptophytes. AU - Skokan, Roman AU - Medvecká, Eva AU - Viaene, Tom AU - Vosolsobě, Stanislav AU - Zwiewka, Marta AU - Müller, Karel AU - Skůpa, Petr AU - Karady, Michal AU - Zhang, Yuzhou AU - Janacek, Dorina P. AU - Hammes, Ulrich Z. AU - Ljung, Karin AU - Nodzyński, Tomasz AU - Petrášek, Jan AU - Friml, Jiří ID - 7106 IS - 11 JF - Nature Plants SN - 2055-0278 TI - PIN-driven auxin transport emerged early in streptophyte evolution VL - 5 ER - TY - JOUR AB - Cell migration is hypothesized to involve a cycle of behaviours beginning with leading edge extension. However, recent evidence suggests that the leading edge may be dispensable for migration, raising the question of what actually controls cell directionality. Here, we exploit the embryonic migration of Drosophila macrophages to bridge the different temporal scales of the behaviours controlling motility. This approach reveals that edge fluctuations during random motility are not persistent and are weakly correlated with motion. In contrast, flow of the actin network behind the leading edge is highly persistent. Quantification of actin flow structure during migration reveals a stable organization and asymmetry in the cell-wide flowfield that strongly correlates with cell directionality. This organization is regulated by a gradient of actin network compression and destruction, which is controlled by myosin contraction and cofilin-mediated disassembly. It is this stable actin-flow polarity, which integrates rapid fluctuations of the leading edge, that controls inherent cellular persistence. AU - Yolland, Lawrence AU - Burki, Mubarik AU - Marcotti, Stefania AU - Luchici, Andrei AU - Kenny, Fiona N. AU - Davis, John Robert AU - Serna-Morales, Eduardo AU - Müller, Jan AU - Sixt, Michael K AU - Davidson, Andrew AU - Wood, Will AU - Schumacher, Linus J. AU - Endres, Robert G. AU - Miodownik, Mark AU - Stramer, Brian M. ID - 7105 IS - 11 JF - Nature Cell Biology SN - 1465-7392 TI - Persistent and polarized global actin flow is essential for directionality during cell migration VL - 21 ER - TY - JOUR AB - We show how to construct temporal testers for the logic MITL, a prominent linear-time logic for real-time systems. A temporal tester is a transducer that inputs a signal holding the Boolean value of atomic propositions and outputs the truth value of a formula along time. Here we consider testers over continuous-time Boolean signals that use clock variables to enforce duration constraints, as in timed automata. We first rewrite the MITL formula into a “simple” formula using a limited set of temporal modalities. We then build testers for these specific modalities and show how to compose testers for simple formulae into complex ones. Temporal testers can be turned into acceptors, yielding a compositional translation from MITL to timed automata. This construction is much simpler than previously known and remains asymptotically optimal. It supports both past and future operators and can easily be extended. AU - Ferrere, Thomas AU - Maler, Oded AU - Ničković, Dejan AU - Pnueli, Amir ID - 7109 IS - 3 JF - Journal of the ACM SN - 0004-5411 TI - From real-time logic to timed automata VL - 66 ER - TY - JOUR AB - We prove that for every d ≥ 2, deciding if a pure, d-dimensional, simplicial complex is shellable is NP-hard, hence NP-complete. This resolves a question raised, e.g., by Danaraj and Klee in 1978. Our reduction also yields that for every d ≥ 2 and k ≥ 0, deciding if a pure, d-dimensional, simplicial complex is k-decomposable is NP-hard. For d ≥ 3, both problems remain NP-hard when restricted to contractible pure d-dimensional complexes. Another simple corollary of our result is that it is NP-hard to decide whether a given poset is CL-shellable. AU - Goaoc, Xavier AU - Patak, Pavel AU - Patakova, Zuzana AU - Tancer, Martin AU - Wagner, Uli ID - 7108 IS - 3 JF - Journal of the ACM SN - 0004-5411 TI - Shellability is NP-complete VL - 66 ER - TY - CONF AB - The expression of a gene is characterised by its transcription factors and the function processing them. If the transcription factors are not affected by gene products, the regulating function is often represented as a combinational logic circuit, where the outputs (product) are determined by current input values (transcription factors) only, and are hence independent on their relative arrival times. However, the simultaneous arrival of transcription factors (TFs) in genetic circuits is a strong assumption, given that the processes of transcription and translation of a gene into a protein introduce intrinsic time delays and that there is no global synchronisation among the arrival times of different molecular species at molecular targets. In this paper, we construct an experimentally implementable genetic circuit with two inputs and a single output, such that, in presence of small delays in input arrival, the circuit exhibits qualitatively distinct observable phenotypes. In particular, these phenotypes are long lived transients: they all converge to a single value, but so slowly, that they seem stable for an extended time period, longer than typical experiment duration. We used rule-based language to prototype our circuit, and we implemented a search for finding the parameter combinations raising the phenotypes of interest. The behaviour of our prototype circuit has wide implications. First, it suggests that GRNs can exploit event timing to create phenotypes. Second, it opens the possibility that GRNs are using event timing to react to stimuli and memorise events, without explicit feedback in regulation. From the modelling perspective, our prototype circuit demonstrates the critical importance of analysing the transient dynamics at the promoter binding sites of the DNA, before applying rapid equilibrium assumptions. AU - Guet, Calin C AU - Henzinger, Thomas A AU - Igler, Claudia AU - Petrov, Tatjana AU - Sezgin, Ali ID - 7147 SN - 0302-9743 T2 - 17th International Conference on Computational Methods in Systems Biology TI - Transient memory in gene regulation VL - 11773 ER - TY - CONF AB - It is well established that the notion of min-entropy fails to satisfy the \emph{chain rule} of the form H(X,Y)=H(X|Y)+H(Y), known for Shannon Entropy. Such a property would help to analyze how min-entropy is split among smaller blocks. Problems of this kind arise for example when constructing extractors and dispersers. We show that any sequence of variables exhibits a very strong strong block-source structure (conditional distributions of blocks are nearly flat) when we \emph{spoil few correlated bits}. This implies, conditioned on the spoiled bits, that \emph{splitting-recombination properties} hold. In particular, we have many nice properties that min-entropy doesn't obey in general, for example strong chain rules, "information can't hurt" inequalities, equivalences of average and worst-case conditional entropy definitions and others. Quantitatively, for any sequence X1,…,Xt of random variables over an alphabet X we prove that, when conditioned on m=t⋅O(loglog|X|+loglog(1/ϵ)+logt) bits of auxiliary information, all conditional distributions of the form Xi|X> 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. AU - Alistarh, Dan-Adrian AU - Nadiradze, Giorgi AU - Koval, Nikita ID - 6673 SN - 9781450361842 T2 - 31st ACM Symposium on Parallelism in Algorithms and Architectures TI - Efficiency guarantees for parallel incremental algorithms under relaxed schedulers ER - TY - JOUR AB - 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. AU - Erdem, Fatma Asli AU - Ilic, Marija AU - Koppensteiner, Peter AU - Gołacki, Jakub AU - Lubec, Gert AU - Freissmuth, Michael AU - Sandtner, Walter ID - 7398 IS - 8 JF - The Journal of General Physiology SN - 0022-1295 TI - A comparison of the transport kinetics of glycine transporter 1 and glycine transporter 2 VL - 151 ER - TY - JOUR AB - 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. AU - Letts, James A AU - Fiedorczuk, Karol AU - Degliesposti, Gianluca AU - Skehel, Mark AU - Sazanov, Leonid A ID - 7395 IS - 6 JF - Molecular Cell SN - 1097-2765 TI - Structures of respiratory supercomplex I+III2 reveal functional and conformational crosstalk VL - 75 ER - TY - JOUR AB - 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. AU - Dura-Bernal, Salvador AU - Suter, Benjamin AU - Gleeson, Padraig AU - Cantarelli, Matteo AU - Quintana, Adrian AU - Rodriguez, Facundo AU - Kedziora, David J AU - Chadderdon, George L AU - Kerr, Cliff C AU - Neymotin, Samuel A AU - McDougal, Robert A AU - Hines, Michael AU - Shepherd, Gordon MG AU - Lytton, William W ID - 7405 JF - eLife SN - 2050-084X TI - NetPyNE, a tool for data-driven multiscale modeling of brain circuits VL - 8 ER - TY - JOUR AB - 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. AU - Veltsos, Paris AU - Ridout, Kate E. AU - Toups, Melissa A AU - González-Martínez, Santiago C. AU - Muyle, Aline AU - Emery, Olivier AU - Rastas, Pasi AU - Hudzieczek, Vojtech AU - Hobza, Roman AU - Vyskot, Boris AU - Marais, Gabriel A. B. AU - Filatov, Dmitry A. AU - Pannell, John R. ID - 7400 IS - 3 JF - Genetics SN - 0016-6731 TI - Early sex-chromosome evolution in the diploid dioecious plant Mercurialis annua VL - 212 ER - TY - JOUR AB - 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. AU - Stürner, Tomke AU - Tatarnikova, Anastasia AU - Müller, Jan AU - Schaffran, Barbara AU - Cuntz, Hermann AU - Zhang, Yun AU - Nemethova, Maria AU - Bogdan, Sven AU - Small, Vic AU - Tavosanis, Gaia ID - 7404 IS - 7 JF - Development SN - 0950-1991 TI - Transient localization of the Arp2/3 complex initiates neuronal dendrite branching in vivo VL - 146 ER - TY - CONF AB - 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. AU - Chatterjee, Krishnendu AU - Doyen, Laurent ID - 7402 SN - 9781728136080 T2 - 34th Annual ACM/IEEE Symposium on Logic in Computer Science TI - Graph planning with expected finite horizon ER - TY - JOUR AB - 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. AU - Vukics, A. AU - Dombi, A. AU - Fink, Johannes M AU - Domokos, P. ID - 7451 JF - Quantum SN - 2521-327X TI - Finite-size scaling of the photon-blockade breakdown dissipative quantum phase transition VL - 3 ER - TY - CONF AB - 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. AU - Swoboda, Paul AU - Kolmogorov, Vladimir ID - 7468 SN - 10636919 T2 - Proceedings of the IEEE Computer Society Conference on Computer Vision and Pattern Recognition TI - Map inference via block-coordinate Frank-Wolfe algorithm VL - 2019-June ER - TY - JOUR AU - Morandell, Jasmin AU - Nicolas, Armel AU - Schwarz, Lena A AU - Novarino, Gaia ID - 7415 IS - Supplement 6 JF - European Neuropsychopharmacology SN - 0924-977X TI - S.16.05 Illuminating the role of the e3 ubiquitin ligase cullin3 in brain development and autism VL - 29 ER - TY - JOUR AU - Knaus, Lisa AU - Tarlungeanu, Dora-Clara AU - Novarino, Gaia ID - 7414 IS - Supplement 6 JF - European Neuropsychopharmacology SN - 0924-977X TI - S.16.03 A homozygous missense mutation in SLC7A5 leads to autism spectrum disorder and microcephaly VL - 29 ER - TY - JOUR AU - Benková, Eva AU - Dagdas, Yasin ID - 7394 IS - 12 JF - Current Opinion in Plant Biology SN - 1369-5266 TI - Editorial overview: Cell biology in the era of omics? VL - 52 ER - TY - CONF AB - 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. AU - Bui Thi Mai, Phuong AU - Lampert, Christoph ID - 7479 SN - 15505499 T2 - IEEE International Conference on Computer Vision TI - Distillation-based training for multi-exit architectures VL - 2019-October ER - TY - CONF AB - We present a novel class of convolutional neural networks (CNNs) for set functions,i.e., data indexed with the powerset of a finite set. The convolutions are derivedas linear, shift-equivariant functions for various notions of shifts on set functions.The framework is fundamentally different from graph convolutions based on theLaplacian, as it provides not one but several basic shifts, one for each element inthe ground set. Prototypical experiments with several set function classificationtasks on synthetic datasets and on datasets derived from real-world hypergraphsdemonstrate the potential of our new powerset CNNs. AU - Wendler, Chris AU - Alistarh, Dan-Adrian AU - Püschel, Markus ID - 7542 SN - 1049-5258 TI - Powerset convolutional neural networks VL - 32 ER - TY - CHAP AB - Social insects (i.e., ants, termites and the social bees and wasps) protect their colonies from disease using a combination of individual immunity and collectively performed defenses, termed social immunity. The first line of social immune defense is sanitary care, which is performed by colony members to protect their pathogen-exposed nestmates from developing an infection. If sanitary care fails and an infection becomes established, a second line of social immune defense is deployed to stop disease transmission within the colony and to protect the valuable queens, which together with the males are the reproductive individuals of the colony. Insect colonies are separated into these reproductive individuals and the sterile worker force, forming a superorganismal reproductive unit reminiscent of the differentiated germline and soma in a multicellular organism. Ultimately, the social immune response preserves the germline of the superorganism insect colony and increases overall fitness of the colony in case of disease. AU - Cremer, Sylvia AU - Kutzer, Megan ED - Choe, Jae ID - 7513 SN - 9780128132517 T2 - Encyclopedia of Animal Behavior TI - Social immunity ER - TY - CONF AB - Bending-active structures are able to efficiently produce complex curved shapes starting from flat panels. The desired deformation of the panels derives from the proper selection of their elastic properties. Optimized panels, called FlexMaps, are designed such that, once they are bent and assembled, the resulting static equilibrium configuration matches a desired input 3D shape. The FlexMaps elastic properties are controlled by locally varying spiraling geometric mesostructures, which are optimized in size and shape to match the global curvature (i.e., bending requests) of the target shape. The design pipeline starts from a quad mesh representing the input 3D shape, which defines the edge size and the total amount of spirals: every quad will embed one spiral. Then, an optimization algorithm tunes the geometry of the spirals by using a simplified pre-computed rod model. This rod model is derived from a non-linear regression algorithm which approximates the non-linear behavior of solid FEM spiral models subject to hundreds of load combinations. This innovative pipeline has been applied to the project of a lightweight plywood pavilion named FlexMaps Pavilion, which is a single-layer piecewise twisted arc that fits a bounding box of 3.90x3.96x3.25 meters. AU - Laccone, Francesco AU - Malomo, Luigi AU - Perez Rodriguez, Jesus AU - Pietroni, Nico AU - Ponchio, Federico AU - Bickel, Bernd AU - Cignoni, Paolo ID - 9261 SN - 2518-6582 T2 - IASS Symposium 2019 - 60th Anniversary Symposium of the International Association for Shell and Spatial Structures; Structural Membranes 2019 - 9th International Conference on Textile Composites and Inflatable Structures, FORM and FORCE TI - FlexMaps Pavilion: A twisted arc made of mesostructured flat flexible panels ER - TY - CONF AB - We propose a new model for detecting visual relationships, such as "person riding motorcycle" or "bottle on table". This task is an important step towards comprehensive structured mage understanding, going beyond detecting individual objects. Our main novelty is a Box Attention mechanism that allows to model pairwise interactions between objects using standard object detection pipelines. The resulting model is conceptually clean, expressive and relies on well-justified training and prediction procedures. Moreover, unlike previously proposed approaches, our model does not introduce any additional complex components or hyperparameters on top of those already required by the underlying detection model. We conduct an experimental evaluation on two datasets, V-COCO and Open Images, demonstrating strong quantitative and qualitative results. AU - Kolesnikov, Alexander AU - Kuznetsova, Alina AU - Lampert, Christoph AU - Ferrari, Vittorio ID - 7640 SN - 9781728150239 T2 - Proceedings of the 2019 International Conference on Computer Vision Workshop TI - Detecting visual relationships using box attention ER - TY - CONF AB - Deep neural networks (DNNs) have become increasingly important due to their excellent empirical performance on a wide range of problems. However, regularization is generally achieved by indirect means, largely due to the complex set of functions defined by a network and the difficulty in measuring function complexity. There exists no method in the literature for additive regularization based on a norm of the function, as is classically considered in statistical learning theory. In this work, we study the tractability of function norms for deep neural networks with ReLU activations. We provide, to the best of our knowledge, the first proof in the literature of the NP-hardness of computing function norms of DNNs of 3 or more layers. We also highlight a fundamental difference between shallow and deep networks. In the light on these results, we propose a new regularization strategy based on approximate function norms, and show its efficiency on a segmentation task with a DNN. AU - Rannen-Triki, Amal AU - Berman, Maxim AU - Kolmogorov, Vladimir AU - Blaschko, Matthew B. ID - 7639 SN - 9781728150239 T2 - Proceedings of the 2019 International Conference on Computer Vision Workshop TI - Function norms for neural networks ER - TY - CHAP AB - We review the history of population genetics, starting with its origins a century ago from the synthesis between Mendel and Darwin's ideas, through to the recent development of sophisticated schemes of inference from sequence data, based on the coalescent. We explain the close relation between the coalescent and a diffusion process, which we illustrate by their application to understand spatial structure. We summarise the powerful methods available for analysis of multiple loci, when linkage equilibrium can be assumed, and then discuss approaches to the more challenging case, where associations between alleles require that we follow genotype, rather than allele, frequencies. Though we can hardly cover the whole of population genetics, we give an overview of the current state of the subject, and future challenges to it. AU - Barton, Nicholas H AU - Etheridge, Alison ED - Balding, David ED - Moltke, Ida ED - Marioni, John ID - 8281 SN - 9781119429142 T2 - Handbook of statistical genomics TI - Mathematical models in population genetics ER - TY - GEN AB - Denote by ∆N the N-dimensional simplex. A map f : ∆N → Rd is an almost r-embedding if fσ1∩. . .∩fσr = ∅ whenever σ1, . . . , σr are pairwise disjoint faces. A counterexample to the topological Tverberg conjecture asserts that if r is not a prime power and d ≥ 2r + 1, then there is an almost r-embedding ∆(d+1)(r−1) → Rd. This was improved by Blagojevi´c–Frick–Ziegler using a simple construction of higher-dimensional counterexamples by taking k-fold join power of lower-dimensional ones. We improve this further (for d large compared to r): If r is not a prime power and N := (d+ 1)r−r l d + 2 r + 1 m−2, then there is an almost r-embedding ∆N → Rd. For the r-fold van Kampen–Flores conjecture we also produce counterexamples which are stronger than previously known. Our proof is based on generalizations of the Mabillard–Wagner theorem on construction of almost r-embeddings from equivariant maps, and of the Ozaydin theorem on existence of equivariant maps. AU - Avvakumov, Sergey AU - Karasev, R. AU - Skopenkov, A. ID - 8184 T2 - arXiv TI - Stronger counterexamples to the topological Tverberg conjecture ER - TY - CONF AB - A proxy re-encryption (PRE) scheme is a public-key encryption scheme that allows the holder of a key pk to derive a re-encryption key for any other key 𝑝𝑘′. This re-encryption key lets anyone transform ciphertexts under pk into ciphertexts under 𝑝𝑘′ without having to know the underlying message, while transformations from 𝑝𝑘′ to pk should not be possible (unidirectional). Security is defined in a multi-user setting against an adversary that gets the users’ public keys and can ask for re-encryption keys and can corrupt users by requesting their secret keys. Any ciphertext that the adversary cannot trivially decrypt given the obtained secret and re-encryption keys should be secure. All existing security proofs for PRE only show selective security, where the adversary must first declare the users it wants to corrupt. This can be lifted to more meaningful adaptive security by guessing the set of corrupted users among the n users, which loses a factor exponential in Open image in new window , rendering the result meaningless already for moderate Open image in new window . Jafargholi et al. (CRYPTO’17) proposed a framework that in some cases allows to give adaptive security proofs for schemes which were previously only known to be selectively secure, while avoiding the exponential loss that results from guessing the adaptive choices made by an adversary. We apply their framework to PREs that satisfy some natural additional properties. Concretely, we give a more fine-grained reduction for several unidirectional PREs, proving adaptive security at a much smaller loss. The loss depends on the graph of users whose edges represent the re-encryption keys queried by the adversary. For trees and chains the loss is quasi-polynomial in the size and for general graphs it is exponential in their depth and indegree (instead of their size as for previous reductions). Fortunately, trees and low-depth graphs cover many, if not most, interesting applications. Our results apply e.g. to the bilinear-map based PRE schemes by Ateniese et al. (NDSS’05 and CT-RSA’09), Gentry’s FHE-based scheme (STOC’09) and the LWE-based scheme by Chandran et al. (PKC’14). AU - Fuchsbauer, Georg AU - Kamath Hosdurg, Chethan AU - Klein, Karen AU - Pietrzak, Krzysztof Z ID - 6430 SN - 03029743 TI - Adaptively secure proxy re-encryption VL - 11443 ER - TY - JOUR AB - 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. AU - Mayzel, Jonathan AU - Steinberg, Victor AU - Varshney, Atul ID - 6069 JF - Nature Communications SN - 2041-1723 TI - Stokes flow analogous to viscous electron current in graphene VL - 10 ER - TY - JOUR AB - 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. AU - Varshney, Atul AU - Steinberg, Victor ID - 6014 JF - Nature Communications SN - 2041-1723 TI - Elastic alfven waves in elastic turbulence VL - 10 ER - TY - JOUR AB - Epidermal growth factor receptor (EGFR) signaling controls skin development and homeostasis inmice and humans, and its deficiency causes severe skin inflammation, which might affect epidermalstem cell behavior. Here, we describe the inflammation-independent effects of EGFR deficiency dur-ing skin morphogenesis and in adult hair follicle stem cells. Expression and alternative splicing analysisof RNA sequencing data from interfollicular epidermis and outer root sheath indicate that EGFR con-trols genes involved in epidermal differentiation and also in centrosome function, DNA damage, cellcycle, and apoptosis. Genetic experiments employingp53deletion in EGFR-deficient epidermis revealthat EGFR signaling exhibitsp53-dependent functions in proliferative epidermal compartments, aswell asp53-independent functions in differentiated hair shaft keratinocytes. Loss of EGFR leads toabsence of LEF1 protein specifically in the innermost epithelial hair layers, resulting in disorganizationof medulla cells. Thus, our results uncover important spatial and temporal features of cell-autonomousEGFR functions in the epidermis. AU - Amberg, Nicole AU - Sotiropoulou, Panagiota A. AU - Heller, Gerwin AU - Lichtenberger, Beate M. AU - Holcmann, Martin AU - Camurdanoglu, Bahar AU - Baykuscheva-Gentscheva, Temenuschka AU - Blanpain, Cedric AU - Sibilia, Maria ID - 6451 JF - iScience SN - 2589-0042 TI - EGFR controls hair shaft differentiation in a p53-independent manner VL - 15 ER - TY - JOUR AB - We study effects of a bounded and compactly supported perturbation on multidimensional continuum random Schrödinger operators in the region of complete localisation. Our main emphasis is on Anderson orthogonality for random Schrödinger operators. Among others, we prove that Anderson orthogonality does occur for Fermi energies in the region of complete localisation with a non-zero probability. This partially confirms recent non-rigorous findings [V. Khemani et al., Nature Phys. 11 (2015), 560–565]. The spectral shift function plays an important role in our analysis of Anderson orthogonality. We identify it with the index of the corresponding pair of spectral projections and explore the consequences thereof. All our results rely on the main technical estimate of this paper which guarantees separate exponential decay of the disorder-averaged Schatten p-norm of χa(f(H)−f(Hτ))χb in a and b. Here, Hτ is a perturbation of the random Schrödinger operator H, χa is the multiplication operator corresponding to the indicator function of a unit cube centred about a∈Rd, and f is in a suitable class of functions of bounded variation with distributional derivative supported in the region of complete localisation for H. AU - Dietlein, Adrian M AU - Gebert, Martin AU - Müller, Peter ID - 10879 IS - 3 JF - Journal of Spectral Theory KW - Random Schrödinger operators KW - spectral shift function KW - Anderson orthogonality SN - 1664-039X TI - Perturbations of continuum random Schrödinger operators with applications to Anderson orthogonality and the spectral shift function VL - 9 ER - TY - JOUR AB - Starting from a microscopic model for a system of neurons evolving in time which individually follow a stochastic integrate-and-fire type model, we study a mean-field limit of the system. Our model is described by a system of SDEs with discontinuous coefficients for the action potential of each neuron and takes into account the (random) spatial configuration of neurons allowing the interaction to depend on it. In the limit as the number of particles tends to infinity, we obtain a nonlinear Fokker-Planck type PDE in two variables, with derivatives only with respect to one variable and discontinuous coefficients. We also study strong well-posedness of the system of SDEs and prove the existence and uniqueness of a weak measure-valued solution to the PDE, obtained as the limit of the laws of the empirical measures for the system of particles. AU - Flandoli, Franco AU - Priola, Enrico AU - Zanco, Giovanni A ID - 10878 IS - 6 JF - Discrete and Continuous Dynamical Systems KW - Applied Mathematics KW - Discrete Mathematics and Combinatorics KW - Analysis SN - 1553-5231 TI - A mean-field model with discontinuous coefficients for neurons with spatial interaction VL - 39 ER - TY - CONF AB - This paper investigates the power of preprocessing in the CONGEST model. Schmid and Suomela (ACM HotSDN 2013) introduced the SUPPORTED CONGEST model to study the application of distributed algorithms in Software-Defined Networks (SDNs). In this paper, we show that a large class of lower bounds in the CONGEST model still hold in the SUPPORTED model, highlighting the robustness of these bounds. This also raises the question how much does preprocessing help in the CONGEST model. AU - Foerster, Klaus-Tycho AU - Korhonen, Janne AU - Rybicki, Joel AU - Schmid, Stefan ID - 6935 SN - 9781450362177 T2 - Proceedings of the 2019 ACM Symposium on Principles of Distributed Computing TI - Does preprocessing help under congestion? ER - TY - JOUR AB - Autoregulation is the direct modulation of gene expression by the product of the corresponding gene. Autoregulation of bacterial gene expression has been mostly studied at the transcriptional level, when a protein acts as the cognate transcriptional repressor. A recent study investigating dynamics of the bacterial toxin–antitoxin MazEF system has shown how autoregulation at both the transcriptional and post-transcriptional levels affects the heterogeneity of Escherichia coli populations. Toxin–antitoxin systems hold a crucial but still elusive part in bacterial response to stress. This perspective highlights how these modules can also serve as a great model system for investigating basic concepts in gene regulation. However, as the genomic background and environmental conditions substantially influence toxin activation, it is important to study (auto)regulation of toxin–antitoxin systems in well-defined setups as well as in conditions that resemble the environmental niche. AU - Nikolic, Nela ID - 138 IS - 1 JF - Current Genetics TI - Autoregulation of bacterial gene expression: lessons from the MazEF toxin–antitoxin system VL - 65 ER - TY - JOUR AB - We construct planar bi-Sobolev mappings whose local volume distortion is bounded from below by a given function f∈Lp with p>1. More precisely, for any 1<q<(p+1)/2 we construct W1,q-bi-Sobolev maps with identity boundary conditions; for f∈L∞, we provide bi-Lipschitz maps. The basic building block of our construction are bi-Lipschitz maps which stretch a given compact subset of the unit square by a given factor while preserving the boundary. The construction of these stretching maps relies on a slight strengthening of the celebrated covering result of Alberti, Csörnyei, and Preiss for measurable planar sets in the case of compact sets. We apply our result to a model functional in nonlinear elasticity, the integrand of which features fast blowup as the Jacobian determinant of the deformation becomes small. For such functionals, the derivation of the equilibrium equations for minimizers requires an additional regularization of test functions, which our maps provide. AU - Fischer, Julian L AU - Kneuss, Olivier ID - 151 IS - 1 JF - Journal of Differential Equations TI - Bi-Sobolev solutions to the prescribed Jacobian inequality in the plane with L p data and applications to nonlinear elasticity VL - 266 ER - TY - JOUR AB - The cerebral cortex is composed of a large variety of distinct cell-types including projection neurons, interneurons and glial cells which emerge from distinct neural stem cell (NSC) lineages. The vast majority of cortical projection neurons and certain classes of glial cells are generated by radial glial progenitor cells (RGPs) in a highly orchestrated manner. Recent studies employing single cell analysis and clonal lineage tracing suggest that NSC and RGP lineage progression are regulated in a profound deterministic manner. In this review we focus on recent advances based mainly on correlative phenotypic data emerging from functional genetic studies in mice. We establish hypotheses to test in future research and outline a conceptual framework how epigenetic cues modulate the generation of cell-type diversity during cortical development. This article is protected by copyright. All rights reserved. AU - Amberg, Nicole AU - Laukoter, Susanne AU - Hippenmeyer, Simon ID - 27 IS - 1 JF - Journal of Neurochemistry TI - Epigenetic cues modulating the generation of cell type diversity in the cerebral cortex VL - 149 ER - TY - JOUR AB - Tissue morphogenesis is driven by mechanical forces that elicit changes in cell size, shape and motion. The extent by which forces deform tissues critically depends on the rheological properties of the recipient tissue. Yet, whether and how dynamic changes in tissue rheology affect tissue morphogenesis and how they are regulated within the developing organism remain unclear. Here, we show that blastoderm spreading at the onset of zebrafish morphogenesis relies on a rapid, pronounced and spatially patterned tissue fluidization. Blastoderm fluidization is temporally controlled by mitotic cell rounding-dependent cell–cell contact disassembly during the last rounds of cell cleavages. Moreover, fluidization is spatially restricted to the central blastoderm by local activation of non-canonical Wnt signalling within the blastoderm margin, increasing cell cohesion and thereby counteracting the effect of mitotic rounding on contact disassembly. Overall, our results identify a fluidity transition mediated by loss of cell cohesion as a critical regulator of embryo morphogenesis. AU - Petridou, Nicoletta AU - Grigolon, Silvia AU - Salbreux, Guillaume AU - Hannezo, Edouard B AU - Heisenberg, Carl-Philipp J ID - 5789 JF - Nature Cell Biology SN - 14657392 TI - Fluidization-mediated tissue spreading by mitotic cell rounding and non-canonical Wnt signalling VL - 21 ER - TY - JOUR AB - The abelian sandpile serves as a model to study self-organized criticality, a phenomenon occurring in biological, physical and social processes. The identity of the abelian group is a fractal composed of self-similar patches, and its limit is subject of extensive collaborative research. Here, we analyze the evolution of the sandpile identity under harmonic fields of different orders. We show that this evolution corresponds to periodic cycles through the abelian group characterized by the smooth transformation and apparent conservation of the patches constituting the identity. The dynamics induced by second and third order harmonics resemble smooth stretchings, respectively translations, of the identity, while the ones induced by fourth order harmonics resemble magnifications and rotations. Starting with order three, the dynamics pass through extended regions of seemingly random configurations which spontaneously reassemble into accentuated patterns. We show that the space of harmonic functions projects to the extended analogue of the sandpile group, thus providing a set of universal coordinates identifying configurations between different domains. Since the original sandpile group is a subgroup of the extended one, this directly implies that it admits a natural renormalization. Furthermore, we show that the harmonic fields can be induced by simple Markov processes, and that the corresponding stochastic dynamics show remarkable robustness over hundreds of periods. Finally, we encode information into seemingly random configurations, and decode this information with an algorithm requiring minimal prior knowledge. Our results suggest that harmonic fields might split the sandpile group into sub-sets showing different critical coefficients, and that it might be possible to extend the fractal structure of the identity beyond the boundaries of its domain. AU - Lang, Moritz AU - Shkolnikov, Mikhail ID - 196 IS - 8 JF - Proceedings of the National Academy of Sciences TI - Harmonic dynamics of the Abelian sandpile VL - 116 ER - TY - CONF AB - Learning disentangled representations is considered a cornerstone problem in representation learning. Recently, Locatello et al. (2019) demonstrated that unsupervised disentanglement learning without inductive biases is theoretically impossible and that existing inductive biases and unsupervised methods do not allow to consistently learn disentangled representations. However, in many practical settings, one might have access to a limited amount of supervision, for example through manual labeling of (some) factors of variation in a few training examples. In this paper, we investigate the impact of such supervision on state-of-the-art disentanglement methods and perform a large scale study, training over 52000 models under well-defined and reproducible experimental conditions. We observe that a small number of labeled examples (0.01--0.5\% of the data set), with potentially imprecise and incomplete labels, is sufficient to perform model selection on state-of-the-art unsupervised models. Further, we investigate the benefit of incorporating supervision into the training process. Overall, we empirically validate that with little and imprecise supervision it is possible to reliably learn disentangled representations. AU - Locatello, Francesco AU - Tschannen, Michael AU - Bauer, Stefan AU - Rätsch, Gunnar AU - Schölkopf, Bernhard AU - Bachem, Olivier ID - 14184 T2 - 8th International Conference on Learning Representations TI - Disentangling factors of variation using few labels ER - TY - CONF AB - We consider the problem of recovering a common latent source with independent components from multiple views. This applies to settings in which a variable is measured with multiple experimental modalities, and where the goal is to synthesize the disparate measurements into a single unified representation. We consider the case that the observed views are a nonlinear mixing of component-wise corruptions of the sources. When the views are considered separately, this reduces to nonlinear Independent Component Analysis (ICA) for which it is provably impossible to undo the mixing. We present novel identifiability proofs that this is possible when the multiple views are considered jointly, showing that the mixing can theoretically be undone using function approximators such as deep neural networks. In contrast to known identifiability results for nonlinear ICA, we prove that independent latent sources with arbitrary mixing can be recovered as long as multiple, sufficiently different noisy views are available. AU - Gresele, Luigi AU - Rubenstein, Paul K. AU - Mehrjou, Arash AU - Locatello, Francesco AU - Schölkopf, Bernhard ID - 14189 T2 - Proceedings of the 35th Conference on Uncertainty in Artificial Intelligence TI - The incomplete Rosetta Stone problem: Identifiability results for multi-view nonlinear ICA VL - 115 ER - TY - CONF AB - Recently there has been a significant interest in learning disentangled representations, as they promise increased interpretability, generalization to unseen scenarios and faster learning on downstream tasks. In this paper, we investigate the usefulness of different notions of disentanglement for improving the fairness of downstream prediction tasks based on representations. We consider the setting where the goal is to predict a target variable based on the learned representation of high-dimensional observations (such as images) that depend on both the target variable and an \emph{unobserved} sensitive variable. We show that in this setting both the optimal and empirical predictions can be unfair, even if the target variable and the sensitive variable are independent. Analyzing the representations of more than \num{12600} trained state-of-the-art disentangled models, we observe that several disentanglement scores are consistently correlated with increased fairness, suggesting that disentanglement may be a useful property to encourage fairness when sensitive variables are not observed. AU - Locatello, Francesco AU - Abbati, Gabriele AU - Rainforth, Tom AU - Bauer, Stefan AU - Schölkopf, Bernhard AU - Bachem, Olivier ID - 14197 SN - 9781713807933 T2 - Advances in Neural Information Processing Systems TI - On the fairness of disentangled representations VL - 32 ER - TY - CONF AB - A broad class of convex optimization problems can be formulated as a semidefinite program (SDP), minimization of a convex function over the positive-semidefinite cone subject to some affine constraints. The majority of classical SDP solvers are designed for the deterministic setting where problem data is readily available. In this setting, generalized conditional gradient methods (aka Frank-Wolfe-type methods) provide scalable solutions by leveraging the so-called linear minimization oracle instead of the projection onto the semidefinite cone. Most problems in machine learning and modern engineering applications, however, contain some degree of stochasticity. In this work, we propose the first conditional-gradient-type method for solving stochastic optimization problems under affine constraints. Our method guarantees O(k−1/3) convergence rate in expectation on the objective residual and O(k−5/12) on the feasibility gap. AU - Locatello, Francesco AU - Yurtsever, Alp AU - Fercoq, Olivier AU - Cevher, Volkan ID - 14191 SN - 9781713807933 T2 - Advances in Neural Information Processing Systems TI - Stochastic Frank-Wolfe for composite convex minimization VL - 32 ER - TY - CONF AB - A disentangled representation encodes information about the salient factors of variation in the data independently. Although it is often argued that this representational format is useful in learning to solve many real-world down-stream tasks, there is little empirical evidence that supports this claim. In this paper, we conduct a large-scale study that investigates whether disentangled representations are more suitable for abstract reasoning tasks. Using two new tasks similar to Raven's Progressive Matrices, we evaluate the usefulness of the representations learned by 360 state-of-the-art unsupervised disentanglement models. Based on these representations, we train 3600 abstract reasoning models and observe that disentangled representations do in fact lead to better down-stream performance. In particular, they enable quicker learning using fewer samples. AU - Steenkiste, Sjoerd van AU - Locatello, Francesco AU - Schmidhuber, Jürgen AU - Bachem, Olivier ID - 14193 SN - 9781713807933 T2 - Advances in Neural Information Processing Systems TI - Are disentangled representations helpful for abstract visual reasoning? VL - 32 ER - TY - CONF AB - The key idea behind the unsupervised learning of disentangled representations is that real-world data is generated by a few explanatory factors of variation which can be recovered by unsupervised learning algorithms. In this paper, we provide a sober look at recent progress in the field and challenge some common assumptions. We first theoretically show that the unsupervised learning of disentangled representations is fundamentally impossible without inductive biases on both the models and the data. Then, we train more than 12000 models covering most prominent methods and evaluation metrics in a reproducible large-scale experimental study on seven different data sets. We observe that while the different methods successfully enforce properties ``encouraged'' by the corresponding losses, well-disentangled models seemingly cannot be identified without supervision. Furthermore, increased disentanglement does not seem to lead to a decreased sample complexity of learning for downstream tasks. Our results suggest that future work on disentanglement learning should be explicit about the role of inductive biases and (implicit) supervision, investigate concrete benefits of enforcing disentanglement of the learned representations, and consider a reproducible experimental setup covering several data sets. AU - Locatello, Francesco AU - Bauer, Stefan AU - Lucic, Mario AU - Rätsch, Gunnar AU - Gelly, Sylvain AU - Schölkopf, Bernhard AU - Bachem, Olivier ID - 14200 T2 - Proceedings of the 36th International Conference on Machine Learning TI - Challenging common assumptions in the unsupervised learning of disentangled representations VL - 97 ER - TY - JOUR AB - We theoretically study the shapes of lipid vesicles confined to a spherical cavity, elaborating a framework based on the so-called limiting shapes constructed from geometrically simple structural elements such as double-membrane walls and edges. Partly inspired by numerical results, the proposed non-compartmentalized and compartmentalized limiting shapes are arranged in the bilayer-couple phase diagram which is then compared to its free-vesicle counterpart. We also compute the area-difference-elasticity phase diagram of the limiting shapes and we use it to interpret shape transitions experimentally observed in vesicles confined within another vesicle. The limiting-shape framework may be generalized to theoretically investigate the structure of certain cell organelles such as the mitochondrion. AU - Kavcic, Bor AU - Sakashita, A. AU - Noguchi, H. AU - Ziherl, P. ID - 5817 IS - 4 JF - Soft Matter SN - 1744-683X TI - Limiting shapes of confined lipid vesicles VL - 15 ER -