TY - CONF AB - 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. AU - Chatterjee, Krishnendu AU - Pavlogiannis, Andreas AU - Toman, Viktor ID - 10190 KW - safety KW - risk KW - reliability and quality KW - software T2 - Proceedings of the 34th ACM International Conference on Object-Oriented Programming, Systems, Languages, and Applications TI - Value-centric dynamic partial order reduction VL - 3 ER - TY - CONF AB - 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. 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 -