TY - JOUR
AB - A new organic–inorganic ferroelectric hybrid capacitor designed by uniformly incorporating surface modified monodisperse 15 nm ferroelectric BaTiO3 nanocubes into non-polar polymer blends of poly(methyl methacrylate) (PMMA) polymer and acrylonitrile-butadiene-styrene (ABS) terpolymer is described. The investigation of spatial distribution of nanofillers via a non-distractive thermal pulse method illustrates that the surface functionalization of nanocubes plays a key role in the uniform distribution of charge polarization within the polymer matrix. The discharged energy density of the nanocomposite with 30 vol% BaTiO3 nanocubes is ∼44 × 10−3 J cm−3, which is almost six times higher than that of the neat polymer. The facile processing, along with the superior mechanical and electrical properties of the BaTiO3/PMMA–ABS nanocomposites make them suitable for implementation into capacitive electrical energy storage devices.
AU - Parizi, Saman Salemizadeh
AU - Conley, Gavin
AU - Costanzo, Tommaso
AU - Howell, Bob
AU - Mellinger, Axel
AU - Caruntu, Gabriel
ID - 7457
IS - 93
JF - RSC Advances
SN - 2046-2069
TI - Fabrication of barium titanate/acrylonitrile-butadiene styrene/poly(methyl methacrylate) nanocomposite films for hybrid ferroelectric capacitors
VL - 5
ER -
TY - JOUR
AB - Currently, there is much debate on the genetic architecture of quantitative traits in wild populations. Is trait variation influenced by many genes of small effect or by a few genes of major effect? Where is additive genetic variation located in the genome? Do the same loci cause similar phenotypic variation in different populations? Great tits (Parus major) have been studied extensively in long‐term studies across Europe and consequently are considered an ecological ‘model organism’. Recently, genomic resources have been developed for the great tit, including a custom SNP chip and genetic linkage map. In this study, we used a suite of approaches to investigate the genetic architecture of eight quantitative traits in two long‐term study populations of great tits—one in the Netherlands and the other in the United Kingdom. Overall, we found little evidence for the presence of genes of large effects in either population. Instead, traits appeared to be influenced by many genes of small effect, with conservative estimates of the number of contributing loci ranging from 31 to 310. Despite concordance between population‐specific heritabilities, we found no evidence for the presence of loci having similar effects in both populations. While population‐specific genetic architectures are possible, an undetected shared architecture cannot be rejected because of limited power to map loci of small and moderate effects. This study is one of few examples of genetic architecture analysis in replicated wild populations and highlights some of the challenges and limitations researchers will face when attempting similar molecular quantitative genetic studies in free‐living populations.
AU - Santure, Anna W.
AU - Poissant, Jocelyn
AU - De Cauwer, Isabelle
AU - van Oers, Kees
AU - Robinson, Matthew Richard
AU - Quinn, John L.
AU - Groenen, Martien A. M.
AU - Visser, Marcel E.
AU - Sheldon, Ben C.
AU - Slate, Jon
ID - 7739
JF - Molecular Ecology
SN - 0962-1083
TI - Replicated analysis of the genetic architecture of quantitative traits in two wild great tit populations
VL - 24
ER -
TY - JOUR
AB - Phenotypes expressed in a social context are not only a function of the individual, but can also be shaped by the phenotypes of social partners. These social effects may play a major role in the evolution of cooperative breeding if social partners differ in the quality of care they provide and if individual carers adjust their effort in relation to that of other carers. When applying social effects models to wild study systems, it is also important to explore sources of individual plasticity that could masquerade as social effects. We studied offspring provisioning rates of parents and helpers in a wild population of long-tailed tits Aegithalos caudatus using a quantitative genetic framework to identify these social effects and partition them into genetic, permanent environment and current environment components. Controlling for other effects, individuals were consistent in their provisioning effort at a given nest, but adjusted their effort based on who was in their social group, indicating the presence of social effects. However, these social effects differed between years and social contexts, indicating a current environment effect, rather than indicating a genetic or permanent environment effect. While this study reveals the importance of examining environmental and genetic sources of social effects, the framework we present is entirely general, enabling a greater understanding of potentially important social effects within any ecological population.
AU - Adams, Mark James
AU - Robinson, Matthew Richard
AU - Mannarelli, Maria-Elena
AU - Hatchwell, Ben J.
ID - 7741
IS - 1810
JF - Proceedings of the Royal Society B: Biological Sciences
SN - 0962-8452
TI - Social genetic and social environment effects on parental and helper care in a cooperatively breeding bird
VL - 282
ER -
TY - JOUR
AB - Across-nation differences in the mean values for complex traits are common1,2,3,4,5,6,7,8, but the reasons for these differences are unknown. Here we find that many independent loci contribute to population genetic differences in height and body mass index (BMI) in 9,416 individuals across 14 European countries. Using discovery data on over 250,000 individuals and unbiased effect size estimates from 17,500 sibling pairs, we estimate that 24% (95% credible interval (CI) = 9%, 41%) and 8% (95% CI = 4%, 16%) of the captured additive genetic variance for height and BMI, respectively, reflect population genetic differences. Population genetic divergence differed significantly from that in a null model (height, P < 3.94 × 10−8; BMI, P < 5.95 × 10−4), and we find an among-population genetic correlation for tall and slender individuals (r = −0.80, 95% CI = −0.95, −0.60), consistent with correlated selection for both phenotypes. Observed differences in height among populations reflected the predicted genetic means (r = 0.51; P < 0.001), but environmental differences across Europe masked genetic differentiation for BMI (P < 0.58).
AU - Robinson, Matthew Richard
AU - Hemani, Gibran
AU - Medina-Gomez, Carolina
AU - Mezzavilla, Massimo
AU - Esko, Tonu
AU - Shakhbazov, Konstantin
AU - Powell, Joseph E
AU - Vinkhuyzen, Anna
AU - Berndt, Sonja I
AU - Gustafsson, Stefan
AU - Justice, Anne E
AU - Kahali, Bratati
AU - Locke, Adam E
AU - Pers, Tune H
AU - Vedantam, Sailaja
AU - Wood, Andrew R
AU - van Rheenen, Wouter
AU - Andreassen, Ole A
AU - Gasparini, Paolo
AU - Metspalu, Andres
AU - Berg, Leonard H van den
AU - Veldink, Jan H
AU - Rivadeneira, Fernando
AU - Werge, Thomas M
AU - Abecasis, Goncalo R
AU - Boomsma, Dorret I
AU - Chasman, Daniel I
AU - de Geus, Eco J C
AU - Frayling, Timothy M
AU - Hirschhorn, Joel N
AU - Hottenga, Jouke Jan
AU - Ingelsson, Erik
AU - Loos, Ruth J F
AU - Magnusson, Patrik K E
AU - Martin, Nicholas G
AU - Montgomery, Grant W
AU - North, Kari E
AU - Pedersen, Nancy L
AU - Spector, Timothy D
AU - Speliotes, Elizabeth K
AU - Goddard, Michael E
AU - Yang, Jian
AU - Visscher, Peter M
ID - 7742
IS - 11
JF - Nature Genetics
SN - 1061-4036
TI - Population genetic differentiation of height and body mass index across Europe
VL - 47
ER -
TY - CONF
AB - High-performance concurrent priority queues are essential for applications such as task scheduling and discrete event simulation. Unfortunately, even the best performing implementations do not scale past a number of threads in the single digits. This is because of the sequential bottleneck in accessing the elements at the head of the queue in order to perform a DeleteMin operation. In this paper, we present the SprayList, a scalable priority queue with relaxed ordering semantics. Starting from a non-blocking SkipList, the main innovation behind our design is that the DeleteMin operations avoid a sequential bottleneck by "spraying" themselves onto the head of the SkipList list in a coordinated fashion. The spraying is implemented using a carefully designed random walk, so that DeleteMin returns an element among the first O(plog3p) in the list, with high probability, where p is the number of threads. We prove that the running time of a DeleteMin operation is O(log3p), with high probability, independent of the size of the list. Our experiments show that the relaxed semantics allow the data structure to scale for high thread counts, comparable to a classic unordered SkipList. Furthermore, we observe that, for reasonably parallel workloads, the scalability benefits of relaxation considerably outweigh the additional work due to out-of-order execution.
AU - Alistarh, Dan-Adrian
AU - Kopinsky, Justin
AU - Li, Jerry
AU - Shavit, Nir
ID - 776
TI - The SprayList: A scalable relaxed priority queue
VL - 2015-January
ER -
TY - JOUR
AB - We introduce a principle unique to disordered solids wherein the contribution of any bond to one global perturbation is uncorrelated with its contribution to another. Coupled with sufficient variability in the contributions of different bonds, this “independent bond-level response” paves the way for the design of real materials with unusual and exquisitely tuned properties. To illustrate this, we choose two global perturbations: compression and shear. By applying a bond removal procedure that is both simple and experimentally relevant to remove a very small fraction of bonds, we can drive disordered spring networks to both the incompressible and completely auxetic limits of mechanical behavior.
AU - Goodrich, Carl Peter
AU - Liu, Andrea J.
AU - Nagel, Sidney R.
ID - 7765
IS - 22
JF - Physical Review Letters
SN - 0031-9007
TI - The principle of independent bond-level response: Tuning by pruning to exploit disorder for global behavior
VL - 114
ER -
TY - JOUR
AB - We study the vibrational properties near a free surface of disordered spring networks derived from jammed sphere packings. In bulk systems, without surfaces, it is well understood that such systems have a plateau in the density of vibrational modes extending down to a frequency scale ω*. This frequency is controlled by ΔZ = 〈Z〉 − 2d, the difference between the average coordination of the spheres and twice the spatial dimension, d, of the system, which vanishes at the jamming transition. In the presence of a free surface we find that there is a density of disordered vibrational modes associated with the surface that extends far below ω*. The total number of these low-frequency surface modes is controlled by ΔZ, and the profile of their decay into the bulk has two characteristic length scales, which diverge as ΔZ−1/2 and ΔZ−1 as the jamming transition is approached.
AU - Sussman, Daniel M.
AU - Goodrich, Carl Peter
AU - Liu, Andrea J.
AU - Nagel, Sidney R.
ID - 7766
IS - 14
JF - Soft Matter
SN - 1744-683X
TI - Disordered surface vibrations in jammed sphere packings
VL - 11
ER -
TY - JOUR
AB - We present a model of soft active particles that leads to a rich array of collective behavior found also in dense biological swarms of bacteria and other unicellular organisms. Our model uses only local interactions, such as Vicsek-type nearest-neighbor alignment, short-range repulsion, and a local boundary term. Changing the relative strength of these interactions leads to migrating swarms, rotating swarms, and jammed swarms, as well as swarms that exhibit run-and-tumble motion, alternating between migration and either rotating or jammed states. Interestingly, although a migrating swarm moves slower than an individual particle, the diffusion constant can be up to three orders of magnitude larger, suggesting that collective motion can be highly advantageous, for example, when searching for food.
AU - van Drongelen, Ruben
AU - Pal, Anshuman
AU - Goodrich, Carl Peter
AU - Idema, Timon
ID - 7767
IS - 3
JF - Physical Review E
SN - 1539-3755
TI - Collective dynamics of soft active particles
VL - 91
ER -
TY - CONF
AB - In many applications, the data is of rich structure that can be represented by a hypergraph, where the data items are represented by vertices and the associations among items are represented by hyperedges. Equivalently, we are given an input bipartite graph with two types of vertices: items, and associations (which we refer to as topics). We consider the problem of partitioning the set of items into a given number of components such that the maximum number of topics covered by a component is minimized. This is a clustering problem with various applications, e.g. partitioning of a set of information objects such as documents, images, and videos, and load balancing in the context of modern computation platforms.Inthis paper, we focus on the streaming computation model for this problem, in which items arrive online one at a time and each item must be assigned irrevocably to a component at its arrival time. Motivated by scalability requirements, we focus on the class of streaming computation algorithms with memory limited to be at most linear in the number of components. We show that a greedy assignment strategy is able to recover a hidden co-clustering of items under a natural set of recovery conditions. We also report results of an extensive empirical evaluation, which demonstrate that this greedy strategy yields superior performance when compared with alternative approaches.
AU - Alistarh, Dan-Adrian
AU - Iglesias, Jennifer
AU - Vojnović, Milan
ID - 777
TI - Streaming min-max hypergraph partitioning
VL - 2015-January
ER -
TY - GEN
AB - The fact that a disordered material is not constrained in its properties in
the same way as a crystal presents significant and yet largely untapped
potential for novel material design. However, unlike their crystalline
counterparts, disordered solids are not well understood. One of the primary
obstacles is the lack of a theoretical framework for thinking about disorder
and its relation to mechanical properties. To this end, we study an idealized
system of frictionless athermal soft spheres that, when compressed, undergoes a
jamming phase transition with diverging length scales and clean power-law
signatures. This critical point is the cornerstone of a much larger "jamming
scenario" that has the potential to provide the essential theoretical
foundation necessary for a unified understanding of the mechanics of disordered
solids. We begin by showing that jammed sphere packings have a valid linear
regime despite the presence of "contact nonlinearities." We then investigate
the critical nature of the transition, focusing on diverging length scales and
finite-size effects. Next, we argue that jamming plays the same role for
disordered solids as the perfect crystal plays for crystalline solids. Not only
can it be considered an idealized starting point for understanding disordered
materials, but it can even influence systems that have a relatively high amount
of crystalline order. The behavior of solids can thus be thought of as existing
on a spectrum, with the perfect crystal and the jamming transition at opposing
ends. Finally, we introduce a new principle wherein the contribution of an
individual bond to one global property is independent of its contribution to
another. This principle allows the different global responses of a disordered
system to be manipulated independently and provides a great deal of flexibility
in designing materials with unique, textured and tunable properties.
AU - Goodrich, Carl Peter
ID - 7779
T2 - arXiv:1510.08820
TI - Unearthing the anticrystal: Criticality in the linear response of disordered solids
ER -
TY - CONF
AB - Several Hybrid Transactional Memory (HyTM) schemes have recently been proposed to complement the fast, but best-effort nature of Hardware Transactional Memory (HTM) with a slow, reliable software backup. However, the costs of providing concurrency between hardware and software transactions in HyTM are still not well understood. In this paper, we propose a general model for HyTM implementations, which captures the ability of hardware transactions to buffer memory accesses. The model allows us to formally quantify and analyze the amount of overhead (instrumentation) caused by the potential presence of software transactions.We prove that (1) it is impossible to build a strictly serializable HyTM implementation that has both uninstrumented reads and writes, even for very weak progress guarantees, and (2) the instrumentation cost incurred by a hardware transaction in any progressive opaque HyTM is linear in the size of the transaction’s data set.We further describe two implementations which exhibit optimal instrumentation costs for two different progress conditions. In sum, this paper proposes the first formal HyTM model and captures for the first time the trade-off between the degree of hardware-software TM concurrency and the amount of instrumentation overhead.
AU - Alistarh, Dan-Adrian
AU - Kopinsky, Justin
AU - Kuznetsov, Petr
AU - Ravi, Srivatsan
AU - Shavit, Nir
ID - 778
TI - Inherent limitations of hybrid transactional memory
VL - 9363
ER -
TY - CONF
AB - The concurrent memory reclamation problem is that of devising a way for a deallocating thread to verify that no other concurrent threads hold references to a memory block being deallocated. To date, in the absence of automatic garbage collection, there is no satisfactory solution to this problem; existing tracking methods like hazard pointers, reference counters, or epoch-based techniques like RCU, are either prohibitively expensive or require significant programming expertise, to the extent that implementing them efficiently can be worthy of a publication. None of the existing techniques are automatic or even semi-automated. In this paper, we take a new approach to concurrent memory reclamation: instead of manually tracking access to memory locations as done in techniques like hazard pointers, or restricting shared accesses to specific epoch boundaries as in RCU, our algorithm, called ThreadScan, leverages operating system signaling to automatically detect which memory locations are being accessed by concurrent threads. Initial empirical evidence shows that ThreadScan scales surprisingly well and requires negligible programming effort beyond the standard use of Malloc and Free.
AU - Alistarh, Dan-Adrian
AU - Matveev, Alexander
AU - Leiserson, William
AU - Shavit, Nir
ID - 779
TI - ThreadScan: Automatic and scalable memory reclamation
VL - 2015-June
ER -
TY - CONF
AB - Population protocols are networks of finite-state agents, interacting randomly, and updating their states using simple rules. Despite their extreme simplicity, these systems have been shown to cooperatively perform complex computational tasks, such as simulating register machines to compute standard arithmetic functions. The election of a unique leader agent is a key requirement in such computational constructions. Yet, the fastest currently known population protocol for electing a leader only has linear convergence time, and it has recently been shown that no population protocol using a constant number of states per node may overcome this linear bound. In this paper, we give the first population protocol for leader election with polylogarithmic convergence time, using polylogarithmic memory states per node. The protocol structure is quite simple: each node has an associated value, and is either a leader (still in contention) or a minion (following some leader). A leader keeps incrementing its value and “defeats” other leaders in one-to-one interactions, and will drop from contention and become a minion if it meets a leader with higher value. Importantly, a leader also drops out if it meets a minion with higher absolute value. While these rules are quite simple, the proof that this algorithm achieves polylogarithmic convergence time is non-trivial. In particular, the argument combines careful use of concentration inequalities with anti-concentration bounds, showing that the leaders’ values become spread apart as the execution progresses, which in turn implies that straggling leaders get quickly eliminated. We complement our analysis with empirical results, showing that our protocol converges extremely fast, even for large network sizes.
AU - Alistarh, Dan-Adrian
AU - Gelashvili, Rati
ID - 780
TI - Polylogarithmic-time leader election in population protocols
VL - 9135
ER -
TY - CONF
AB - Population protocols, roughly defined as systems consisting of large numbers of simple identical agents, interacting at random and updating their state following simple rules, are an important research topic at the intersection of distributed computing and biology. One of the fundamental tasks that a population protocol may solve is majority: each node starts in one of two states; the goal is for all nodes to reach a correct consensus on which of the two states was initially the majority. Despite considerable research effort, known protocols for this problem are either exact but slow (taking linear parallel time to converge), or fast but approximate (with non-zero probability of error). In this paper, we show that this trade-off between preciasion and speed is not inherent. We present a new protocol called Average and Conquer (AVC) that solves majority ex-actly in expected parallel convergence time O(log n/(sε) + log n log s), where n is the number of nodes, εn is the initial node advantage of the majority state, and s = Ω(log n log log n) is the number of states the protocol employs. This shows that the majority problem can be solved exactly in time poly-logarithmic in n, provided that the memory per node is s = Ω(1/ε + lognlog1/ε). On the negative side, we establish a lower bound of Ω(1/ε) on the expected paraallel convergence time for the case of four memory states per node, and a lower bound of Ω(logn) parallel time for protocols using any number of memory states per node.per node, and a lower bound of (log n) parallel time for protocols using any number of memory states per node.
AU - Alistarh, Dan-Adrian
AU - Gelashvili, Rati
AU - Vojnović, Milan
ID - 781
TI - Fast and exact majority in population protocols
VL - 2015-July
ER -
TY - CONF
AB - In this work, we consider the following random process, mo- Tivated by the analysis of lock-free concurrent algorithms under high memory contention. In each round, a new scheduling step is allocated to one of n threads, according to a distribution p = (p1; p2; : : : ; pn), where thread i is scheduled with probability pi. When some thread first reaches a set threshold of executed steps, it registers a win, completing its current operation, and resets its step count to 1. At the same time, threads whose step count was close to the threshold also get reset because of the win, but to 0 steps, being penalized for almost winning. We are interested in two questions: how often does some thread complete an operation (system latency), and how often does a specific thread complete an operation (individual latency)? We provide asymptotically tight bounds for the system and individual latency of this general concurrency pattern, for arbitrary scheduling distributions p. Surprisingly, a sim- ple characterization exists: in expectation, the system will complete a new operation every Θ(1/p 2) steps, while thread i will complete a new operation every Θ(1/2=p i ) steps. The proof is interesting in its own right, as it requires a careful analysis of how the higher norms of the vector p inuence the thread step counts and latencies in this random process. Our result offers a simple connection between the scheduling distribution and the average performance of concurrent algorithms, which has several applications.
AU - Alistarh, Dan-Adrian
AU - Sauerwald, Thomas
AU - Vojnović, Milan
ID - 782
TI - Lock-Free algorithms under stochastic schedulers
VL - 2015-July
ER -
TY - CONF
AB - The problem of electing a leader from among n contenders is one of the fundamental questions in distributed computing. In its simplest formulation, the task is as follows: given n processors, all participants must eventually return a win or lose indication, such that a single contender may win. Despite a considerable amount of work on leader election, the following question is still open: can we elect a leader in an asynchronous fault-prone system faster than just running a Θ(log n)-time tournament, against a strong adaptive adversary? In this paper, we answer this question in the affirmative, improving on a decades-old upper bound. We introduce two new algorithmic ideas to reduce the time complexity of electing a leader to O(log∗ n), using O(n2) point-to-point messages. A non-trivial application of our algorithm is a new upper bound for the tight renaming problem, assigning n items to the n participants in expected O(log2 n) time and O(n2) messages. We complement our results with lower bound of Ω(n2) messages for solving these two problems, closing the question of their message complexity.
AU - Alistarh, Dan-Adrian
AU - Gelashvili, Rati
AU - Vladu, Adrian
ID - 783
TI - How to elect a leader faster than a tournament
VL - 2015-July
ER -
TY - CONF
AB - We demonstrate an optical switch design that can scale up to a thousand ports with high per-port bandwidth (25 Gbps+) and low switching latency (40 ns). Our design uses a broadcast and select architecture, based on a passive star coupler and fast tunable transceivers. In addition we employ time division multiplexing to achieve very low switching latency. Our demo shows the feasibility of the switch data plane using a small testbed, comprising two transmitters and a receiver, connected through a star coupler.
AU - Alistarh, Dan-Adrian
AU - Ballani, Hitesh
AU - Costa, Paolo
AU - Funnell, Adam
AU - Benjamin, Joshua
AU - Watts, Philip
AU - Thomsen, Benn
ID - 784
SN - 978-1-4503-3542-3
TI - A high-radix, low-latency optical switch for data centers
ER -
TY - JOUR
AB - We prove that nonlinear Gibbs measures can be obtained from the corresponding many-body, grand-canonical, quantum Gibbs states, in a mean-field limit where the temperature T diverges and the interaction strength behaves as 1/T. We proceed by characterizing the interacting Gibbs state as minimizing a functional counting the free-energy relatively to the non-interacting case. We then perform an infinite-dimensional analogue of phase-space semiclassical analysis, using fine properties of the quantum relative entropy, the link between quantum de Finetti measures and upper/lower symbols in a coherent state basis, as well as Berezin-Lieb type inequalities. Our results cover the measure built on the defocusing nonlinear Schrödinger functional on a finite interval, as well as smoother interactions in dimensions d 2.
AU - Lewin, Mathieu
AU - Phan Thanh, Nam
AU - Rougerie, Nicolas
ID - 473
JF - Journal de l'Ecole Polytechnique - Mathematiques
TI - Derivation of nonlinear gibbs measures from many-body quantum mechanics
VL - 2
ER -
TY - JOUR
AB - Dendritic cells are potent antigen-presenting cells endowed with the unique ability to initiate adaptive immune responses upon inflammation. Inflammatory processes are often associated with an increased production of serotonin, which operates by activating specific receptors. However, the functional role of serotonin receptors in regulation of dendritic cell functions is poorly understood. Here, we demonstrate that expression of serotonin receptor 5-HT7 (5-HT7TR) as well as its downstream effector Cdc42 is upregulated in dendritic cells upon maturation. Although dendritic cell maturation was independent of 5-HT7TR, receptor stimulation affected dendritic cell morphology through Cdc42-mediated signaling. In addition, basal activity of 5-HT7TR was required for the proper expression of the chemokine receptor CCR7, which is a key factor that controls dendritic cell migration. Consistent with this, we observed that 5-HT7TR enhances chemotactic motility of dendritic cells in vitro by modulating their directionality and migration velocity. Accordingly, migration of dendritic cells in murine colon explants was abolished after pharmacological receptor inhibition. Our results indicate that there is a crucial role for 5-HT7TR-Cdc42-mediated signaling in the regulation of dendritic cell morphology and motility, suggesting that 5-HT7TR could be a new target for treatment of a variety of inflammatory and immune disorders.
AU - Holst, Katrin
AU - Guseva, Daria
AU - Schindler, Susann
AU - Sixt, Michael K
AU - Braun, Armin
AU - Chopra, Himpriya
AU - Pabst, Oliver
AU - Ponimaskin, Evgeni
ID - 477
IS - 15
JF - Journal of Cell Science
TI - The serotonin receptor 5-HT7R regulates the morphology and migratory properties of dendritic cells
VL - 128
ER -
TY - JOUR
AB - We consider two-player games played on weighted directed graphs with mean-payoff and total-payoff objectives, two classical quantitative objectives. While for single-dimensional games the complexity and memory bounds for both objectives coincide, we show that in contrast to multi-dimensional mean-payoff games that are known to be coNP-complete, multi-dimensional total-payoff games are undecidable. We introduce conservative approximations of these objectives, where the payoff is considered over a local finite window sliding along a play, instead of the whole play. For single dimension, we show that (i) if the window size is polynomial, deciding the winner takes polynomial time, and (ii) the existence of a bounded window can be decided in NP ∩ coNP, and is at least as hard as solving mean-payoff games. For multiple dimensions, we show that (i) the problem with fixed window size is EXPTIME-complete, and (ii) there is no primitive-recursive algorithm to decide the existence of a bounded window.
AU - Chatterjee, Krishnendu
AU - Doyen, Laurent
AU - Randour, Mickael
AU - Raskin, Jean
ID - 523
IS - 6
JF - Information and Computation
TI - Looking at mean-payoff and total-payoff through windows
VL - 242
ER -
TY - JOUR
AB - We consider concurrent games played by two players on a finite-state graph, where in every round the players simultaneously choose a move, and the current state along with the joint moves determine the successor state. We study the most fundamental objective for concurrent games, namely, mean-payoff or limit-average objective, where a reward is associated to each transition, and the goal of player 1 is to maximize the long-run average of the rewards, and the objective of player 2 is strictly the opposite (i.e., the games are zero-sum). The path constraint for player 1 could be qualitative, i.e., the mean-payoff is the maximal reward, or arbitrarily close to it; or quantitative, i.e., a given threshold between the minimal and maximal reward. We consider the computation of the almost-sure (resp. positive) winning sets, where player 1 can ensure that the path constraint is satisfied with probability 1 (resp. positive probability). Almost-sure winning with qualitative constraint exactly corresponds to the question of whether there exists a strategy to ensure that the payoff is the maximal reward of the game. Our main results for qualitative path constraints are as follows: (1) we establish qualitative determinacy results that show that for every state either player 1 has a strategy to ensure almost-sure (resp. positive) winning against all player-2 strategies, or player 2 has a spoiling strategy to falsify almost-sure (resp. positive) winning against all player-1 strategies; (2) we present optimal strategy complexity results that precisely characterize the classes of strategies required for almost-sure and positive winning for both players; and (3) we present quadratic time algorithms to compute the almost-sure and the positive winning sets, matching the best known bound of the algorithms for much simpler problems (such as reachability objectives). For quantitative constraints we show that a polynomial time solution for the almost-sure or the positive winning set would imply a solution to a long-standing open problem (of solving the value problem of turn-based deterministic mean-payoff games) that is not known to be solvable in polynomial time.
AU - Chatterjee, Krishnendu
AU - Ibsen-Jensen, Rasmus
ID - 524
IS - 6
JF - Information and Computation
TI - Qualitative analysis of concurrent mean payoff games
VL - 242
ER -
TY - JOUR
AB - Ethylene is a gaseous phytohormone that plays vital roles in plant growth and development. Previous studies uncovered EIN2 as an essential signal transducer linking ethylene perception on ER to transcriptional regulation in the nucleus through a “cleave and shuttle” model. In this study, we report another mechanism of EIN2-mediated ethylene signaling, whereby EIN2 imposes the translational repression of EBF1 and EBF2 mRNA. We find that the EBF1/2 3′ UTRs mediate EIN2-directed translational repression and identify multiple poly-uridylates (PolyU) motifs as functional cis elements of 3′ UTRs. Furthermore, we demonstrate that ethylene induces EIN2 to associate with 3′ UTRs and target EBF1/2 mRNA to cytoplasmic processing-body (P-body) through interacting with multiple P-body factors, including EIN5 and PABs. Our study illustrates translational regulation as a key step in ethylene signaling and presents mRNA 3′ UTR functioning as a “signal transducer” to sense and relay cellular signaling in plants.
AU - Li, Wenyang
AU - Ma, Mengdi
AU - Feng, Ying
AU - Li, Hongjiang
AU - Wang, Yichuan
AU - Ma, Yutong
AU - Li, Mingzhe
AU - An, Fengying
AU - Guo, Hongwei
ID - 532
IS - 3
JF - Cell
TI - EIN2-directed translational regulation of ethylene signaling in arabidopsis
VL - 163
ER -
TY - GEN
AB - We consider Markov decision processes (MDPs) with multiple limit-average (or mean-payoff) objectives.
There have been two different views: (i) the expectation semantics, where the goal is to optimize the expected mean-payoff objective, and (ii) the satisfaction semantics, where the goal is to maximize the probability of runs such that the mean-payoff value stays above a given vector.
We consider the problem where the goal is to optimize the expectation under the constraint that the satisfaction semantics is ensured, and thus consider a generalization that unifies the existing semantics.
Our problem captures the notion of optimization with respect to strategies that are risk-averse (i.e., ensures certain probabilistic guarantee).
Our main results are algorithms for the decision problem which are always polynomial in the size of the MDP. We also show that an approximation of the Pareto-curve can be computed in time polynomial in the size of the MDP, and the approximation factor, but exponential in the number of dimensions.
Finally, we present a complete characterization of the strategy complexity (in terms of memory bounds and randomization) required to solve our problem.
AU - Chatterjee, Krishnendu
AU - Komarkova, Zuzana
AU - Kretinsky, Jan
ID - 5429
SN - 2664-1690
TI - Unifying two views on multiple mean-payoff objectives in Markov decision processes
ER -
TY - GEN
AB - We consider the core algorithmic problems related to verification of systems with respect to three classical quantitative properties, namely, the mean- payoff property, the ratio property, and the minimum initial credit for energy property. The algorithmic problem given a graph and a quantitative property asks to compute the optimal value (the infimum value over all traces) from every node of the graph. We consider graphs with constant treewidth, and it is well-known that the control-flow graphs of most programs have constant treewidth. Let n denote the number of nodes of a graph, m the number of edges (for constant treewidth graphs m = O ( n ) ) and W the largest absolute value of the weights. Our main theoretical results are as follows. First, for constant treewidth graphs we present an algorithm that approximates the mean-payoff value within a mul- tiplicative factor of ∊ in time O ( n · log( n/∊ )) and linear space, as compared to the classical algorithms that require quadratic time. Second, for the ratio property we present an algorithm that for constant treewidth graphs works in time O ( n · log( | a · b · n | )) = O ( n · log( n · W )) , when the output is a b , as compared to the previously best known algorithm with running time O ( n 2 · log( n · W )) . Third, for the minimum initial credit problem we show that (i) for general graphs the problem can be solved in O ( n 2 · m ) time and the associated decision problem can be solved in O ( n · m ) time, improving the previous known O ( n 3 · m · log( n · W )) and O ( n 2 · m ) bounds, respectively; and (ii) for constant treewidth graphs we present an algorithm that requires O ( n · log n ) time, improving the previous known O ( n 4 · log( n · W )) bound. We have implemented some of our algorithms and show that they present a significant speedup on standard benchmarks.
AU - Chatterjee, Krishnendu
AU - Ibsen-Jensen, Rasmus
AU - Pavlogiannis, Andreas
ID - 5430
SN - 2664-1690
TI - Faster algorithms for quantitative verification in constant treewidth graphs
ER -
TY - GEN
AB - We consider finite-state concurrent stochastic games, played by k>=2 players for an infinite number of rounds, where in every round, each player simultaneously and independently of the other players chooses an action, whereafter the successor state is determined by a probability distribution given by the current state and the chosen actions. We consider reachability objectives that given a target set of states require that some state in the target set is visited, and the dual safety objectives that given a target set require that only states in the target set are visited. We are interested in the complexity of stationary strategies measured by their patience, which is defined as the inverse of the smallest non-zero probability employed.
Our main results are as follows: We show that in two-player zero-sum concurrent stochastic games (with reachability objective for one player and the complementary safety objective for the other player): (i) the optimal bound on the patience of optimal and epsilon-optimal strategies, for both players is doubly exponential; and (ii) even in games with a single non-absorbing state exponential (in the number of actions) patience is necessary. In general we study the class of non-zero-sum games admitting epsilon-Nash equilibria. We show that if there is at least one player with reachability objective, then doubly-exponential patience is needed in general for epsilon-Nash equilibrium strategies, whereas in contrast if all players have safety objectives, then the optimal bound on patience for epsilon-Nash equilibrium strategies is only exponential.
AU - Chatterjee, Krishnendu
AU - Ibsen-Jensen, Rasmus
AU - Hansen, Kristoffer
ID - 5431
SN - 2664-1690
TI - The patience of concurrent stochastic games with safety and reachability objectives
ER -
TY - GEN
AB - Evolution occurs in populations of reproducing individuals. The structure of the population affects the outcome of the evolutionary process. Evolutionary graph theory is a powerful approach to study this phenomenon. There are two graphs. The interaction graph specifies who interacts with whom in the context of evolution.The replacement graph specifies who competes with whom for reproduction.
The vertices of the two graphs are the same, and each vertex corresponds to an individual of the population. A key quantity is the fixation probability of a new mutant. It is defined as the probability that a newly introduced mutant (on a single vertex) generates a lineage of offspring which eventually takes over the entire population of resident individuals. The basic computational questions are as follows: (i) the qualitative question asks whether the fixation probability is positive; and (ii) the quantitative approximation question asks for an approximation of the fixation probability.
Our main results are:
(1) We show that the qualitative question is NP-complete and the quantitative approximation question is #P-hard in the special case when the interaction and the replacement graphs coincide and even with the restriction that the resident individuals do not reproduce (which corresponds to an invading population taking over an empty structure).
(2) We show that in general the qualitative question is PSPACE-complete and the quantitative approximation question is PSPACE-hard and can be solved in exponential time.
AU - Chatterjee, Krishnendu
AU - Ibsen-Jensen, Rasmus
AU - Nowak, Martin
ID - 5432
SN - 2664-1690
TI - The complexity of evolutionary games on graphs
ER -
TY - GEN
AB - DEC-POMDPs extend POMDPs to a multi-agent setting, where several agents operate in an uncertain environment independently to achieve a joint objective. DEC-POMDPs have been studied with finite-horizon and infinite-horizon discounted-sum objectives, and there exist solvers both for exact and approximate solutions. In this work we consider Goal-DEC-POMDPs, where given a set of target states, the objective is to ensure that the target set is reached with minimal cost. We consider the indefinite-horizon (infinite-horizon with either discounted-sum, or undiscounted-sum, where absorbing goal states have zero-cost) problem. We present a new method to solve the problem that extends methods for finite-horizon DEC- POMDPs and the RTDP-Bel approach for POMDPs. We present experimental results on several examples, and show our approach presents promising results.
AU - Anonymous, 1
AU - Anonymous, 2
ID - 5434
SN - 2664-1690
TI - Optimal cost indefinite-horizon reachability in goal DEC-POMDPs
ER -
TY - GEN
AB - We consider Markov decision processes (MDPs) with multiple limit-average (or mean-payoff) objectives.
There have been two different views: (i) the expectation semantics, where the goal is to optimize the expected mean-payoff objective, and (ii) the satisfaction semantics, where the goal is to maximize the probability of runs such that the mean-payoff value stays above a given vector.
We consider the problem where the goal is to optimize the expectation under the constraint that the satisfaction semantics is ensured, and thus consider a generalization that unifies the existing semantics. Our problem captures the notion of optimization with respect to strategies that are risk-averse (i.e., ensures certain probabilistic guarantee).
Our main results are algorithms for the decision problem which are always polynomial in the size of the MDP.
We also show that an approximation of the Pareto-curve can be computed in time polynomial in the size of the MDP, and the approximation factor, but exponential in the number of dimensions. Finally, we present a complete characterization of the strategy complexity (in terms of memory bounds and randomization) required to solve our problem.
AU - Chatterjee, Krishnendu
AU - Komarkova, Zuzana
AU - Kretinsky, Jan
ID - 5435
SN - 2664-1690
TI - Unifying two views on multiple mean-payoff objectives in Markov decision processes
ER -
TY - GEN
AB - Recently there has been a significant effort to handle quantitative properties in formal verification and synthesis. While weighted automata over finite and infinite words provide a natural and flexible framework to express quantitative properties, perhaps surprisingly, some basic system properties such as average response time cannot be expressed using weighted automata, nor in any other know decidable formalism. In this work, we introduce nested weighted automata as a natural extension of weighted automata which makes it possible to express important quantitative properties such as average response time.
In nested weighted automata, a master automaton spins off and collects results from weighted slave automata, each of which computes a quantity along a finite portion of an infinite word. Nested weighted automata can be viewed as the quantitative analogue of monitor automata, which are used in run-time verification. We establish an almost complete decidability picture for the basic decision problems about nested weighted automata, and illustrate their applicability in several domains. In particular, nested weighted automata can be used to decide average response time properties.
AU - Chatterjee, Krishnendu
AU - Henzinger, Thomas A
AU - Otop, Jan
ID - 5436
SN - 2664-1690
TI - Nested weighted automata
ER -
TY - GEN
AB - We consider the core algorithmic problems related to verification of systems with respect to three classical quantitative properties, namely, the mean-payoff property, the ratio property, and the minimum initial credit for energy property.
The algorithmic problem given a graph and a quantitative property asks to compute the optimal value (the infimum value over all traces) from every node of the graph. We consider graphs with constant treewidth, and it is well-known that the control-flow graphs of most programs have constant treewidth. Let $n$ denote the number of nodes of a graph, $m$ the number of edges (for constant treewidth graphs $m=O(n)$) and $W$ the largest absolute value of the weights.
Our main theoretical results are as follows.
First, for constant treewidth graphs we present an algorithm that approximates the mean-payoff value within a multiplicative factor of $\epsilon$ in time $O(n \cdot \log (n/\epsilon))$ and linear space, as compared to the classical algorithms that require quadratic time. Second, for the ratio property we present an algorithm that for constant treewidth graphs works in time $O(n \cdot \log (|a\cdot b|))=O(n\cdot\log (n\cdot W))$, when the output is $\frac{a}{b}$, as compared to the previously best known algorithm with running time $O(n^2 \cdot \log (n\cdot W))$. Third, for the minimum initial credit problem we show that (i)~for general graphs the problem can be solved in $O(n^2\cdot m)$ time and the associated decision problem can be solved in $O(n\cdot m)$ time, improving the previous known $O(n^3\cdot m\cdot \log (n\cdot W))$ and $O(n^2 \cdot m)$ bounds, respectively; and (ii)~for constant treewidth graphs we present an algorithm that requires $O(n\cdot \log n)$ time, improving the previous known $O(n^4 \cdot \log (n \cdot W))$ bound.
We have implemented some of our algorithms and show that they present a significant speedup on standard benchmarks.
AU - Chatterjee, Krishnendu
AU - Ibsen-Jensen, Rasmus
AU - Pavlogiannis, Andreas
ID - 5437
SN - 2664-1690
TI - Faster algorithms for quantitative verification in constant treewidth graphs
ER -
TY - GEN
AB - The edit distance between two words w1, w2 is the minimal number of word operations (letter insertions, deletions, and substitutions) necessary to transform w1 to w2. The edit distance generalizes to languages L1, L2, where the edit distance is the minimal number k such that for every word from L1 there exists a word in L2 with edit distance at most k. We study the edit distance computation problem between pushdown automata and their subclasses.
The problem of computing edit distance to a pushdown automaton is undecidable, and in practice, the interesting question is to compute the edit distance from a pushdown automaton (the implementation, a standard model for programs with recursion) to a regular language (the specification). In this work, we present a complete picture of decidability and complexity for deciding whether, for a given threshold k, the edit distance from a pushdown automaton to a finite automaton is at most k.
AU - Chatterjee, Krishnendu
AU - Henzinger, Thomas A
AU - Ibsen-Jensen, Rasmus
AU - Otop, Jan
ID - 5438
SN - 2664-1690
TI - Edit distance for pushdown automata
ER -
TY - GEN
AB - The target discounted-sum problem is the following: Given a rational discount factor 0 < λ < 1 and three rational values a, b, and t, does there exist a finite or an infinite sequence w ε(a, b)∗ or w ε(a, b)w, such that Σ|w| i=0 w(i)λi equals t? The problem turns out to relate to many fields of mathematics and computer science, and its decidability question is surprisingly hard to solve. We solve the finite version of the problem, and show the hardness of the infinite version, linking it to various areas and open problems in mathematics and computer science: β-expansions, discounted-sum automata, piecewise affine maps, and generalizations of the Cantor set. We provide some partial results to the infinite version, among which are solutions to its restriction to eventually-periodic sequences and to the cases that λ λ 1/2 or λ = 1/n, for every n ε N. We use our results for solving some open problems on discounted-sum automata, among which are the exact-value problem for nondeterministic automata over finite words and the universality and inclusion problems for functional automata.
AU - Boker, Udi
AU - Henzinger, Thomas A
AU - Otop, Jan
ID - 5439
SN - 2664-1690
TI - The target discounted-sum problem
ER -
TY - GEN
AB - Evolution occurs in populations of reproducing individuals. The structure of the population affects the outcome of the evolutionary process. Evolutionary graph theory is a powerful approach to study this phenomenon. There are two graphs. The interaction graph specifies who interacts with whom for payoff in the context of evolution. The replacement graph specifies who competes with whom for reproduction. The vertices of the two graphs are the same, and each vertex corresponds to an individual of the population. The fitness (or the reproductive rate) is a non-negative number, and depends on the payoff. A key quantity is the fixation probability of a new mutant. It is defined as the probability that a newly introduced mutant (on a single vertex) generates a lineage of offspring which eventually takes over the entire population of resident individuals. The basic computational questions are as follows: (i) the qualitative question asks whether the fixation probability is positive; and (ii) the quantitative approximation question asks for an approximation of the fixation probability. Our main results are as follows: First, we consider a special case of the general problem, where the residents do not reproduce. We show that the qualitative question is NP-complete, and the quantitative approximation question is #P-complete, and the hardness results hold even in the special case where the interaction and the replacement graphs coincide. Second, we show that in general both the qualitative and the quantitative approximation questions are PSPACE-complete. The PSPACE-hardness result for quantitative approximation holds even when the fitness is always positive.
AU - Chatterjee, Krishnendu
AU - Ibsen-Jensen, Rasmus
AU - Nowak, Martin
ID - 5440
SN - 2664-1690
TI - The complexity of evolutionary games on graphs
ER -
TY - GEN
AB - We study algorithmic questions for concurrent systems where the transitions are labeled from a complete, closed semiring, and path properties are algebraic with semiring operations. The algebraic path properties can model dataflow analysis problems, the shortest path problem, and many other natural problems that arise in program analysis. We consider that each component of the concurrent system is a graph with constant treewidth, a property satisfied by the controlflow graphs of most programs. We allow for multiple possible queries, which arise naturally in demand driven dataflow analysis. The study of multiple queries allows us to consider the tradeoff between the resource usage of the one-time preprocessing and for each individual query. The traditional approach constructs the product graph of all components and applies the best-known graph algorithm on the product. In this approach, even the answer to a single query requires the transitive closure (i.e., the results of all possible queries), which provides no room for tradeoff between preprocessing and query time. Our main contributions are algorithms that significantly improve the worst-case running time of the traditional approach, and provide various tradeoffs depending on the number of queries. For example, in a concurrent system of two components, the traditional approach requires hexic time in the worst case for answering one query as well as computing the transitive closure, whereas we show that with one-time preprocessing in almost cubic time, each subsequent query can be answered in at most linear time, and even the transitive closure can be computed in almost quartic time. Furthermore, we establish conditional optimality results showing that the worst-case running time of our algorithms cannot be improved without achieving major breakthroughs in graph algorithms (i.e., improving the worst-case bound for the shortest path problem in general graphs). Preliminary experimental results show that our algorithms perform favorably on several benchmarks.
AU - Chatterjee, Krishnendu
AU - Ibsen-Jensen, Rasmus
AU - Goharshady, Amir
AU - Pavlogiannis, Andreas
ID - 5441
SN - 2664-1690
TI - Algorithms for algebraic path properties in concurrent systems of constant treewidth components
ER -
TY - GEN
AB - We study algorithmic questions for concurrent systems where the transitions are labeled from a complete, closed semiring, and path properties are algebraic with semiring operations. The algebraic path properties can model dataflow analysis problems, the shortest path problem, and many other natural properties that arise in program analysis.
We consider that each component of the concurrent system is a graph with constant treewidth, and it is known that the controlflow graphs of most programs have constant treewidth. We allow for multiple possible queries, which arise naturally in demand driven dataflow analysis problems (e.g., alias analysis). The study of multiple queries allows us to consider the tradeoff between the resource usage of the \emph{one-time} preprocessing and for \emph{each individual} query. The traditional approaches construct the product graph of all components and apply the best-known graph algorithm on the product. In the traditional approach, even the answer to a single query requires the transitive closure computation (i.e., the results of all possible queries), which provides no room for tradeoff between preprocessing and query time.
Our main contributions are algorithms that significantly improve the worst-case running time of the traditional approach, and provide various tradeoffs depending on the number of queries. For example, in a concurrent system of two components, the traditional approach requires hexic time in the worst case for answering one query as well as computing the transitive closure, whereas we show that with one-time preprocessing in almost cubic time,
each subsequent query can be answered in at most linear time, and even the transitive closure can be computed in almost quartic time. Furthermore, we establish conditional optimality results that show that the worst-case running times of our algorithms cannot be improved without achieving major breakthroughs in graph algorithms (such as improving
the worst-case bounds for the shortest path problem in general graphs whose current best-known bound has not been improved in five decades). Finally, we provide a prototype implementation of our algorithms which significantly outperforms the existing algorithmic methods on several benchmarks.
AU - Anonymous, 1
AU - Anonymous, 2
AU - Anonymous, 3
AU - Anonymous, 4
ID - 5442
SN - 2664-1690
TI - Algorithms for algebraic path properties in concurrent systems of constant treewidth components
ER -
TY - GEN
AB - POMDPs are standard models for probabilistic planning problems, where an agent interacts with an uncertain environment. We study the problem of almost-sure reachability, where given a set of target states, the question is to decide whether there is a policy to ensure that the target set is reached with probability 1 (almost-surely). While in general the problem is EXPTIME-complete, in many practical cases policies with a small amount of memory suffice. Moreover, the existing solution to the problem is explicit, which first requires to construct explicitly an exponential reduction to a belief-support MDP. In this work, we first study the existence of observation-stationary strategies, which is NP-complete, and then small-memory strategies. We present a symbolic algorithm by an efficient encoding to SAT and using a SAT solver for the problem. We report experimental results demonstrating the scalability of our symbolic (SAT-based) approach.
AU - Chatterjee, Krishnendu
AU - Chmelik, Martin
AU - Davies, Jessica
ID - 5443
SN - 2664-1690
TI - A symbolic SAT-based algorithm for almost-sure reachability with small strategies in POMDPs
ER -
TY - GEN
AB - A comprehensive understanding of the clonal evolution of cancer is critical for understanding neoplasia. Genome-wide sequencing data enables evolutionary studies at unprecedented depth. However, classical phylogenetic methods often struggle with noisy sequencing data of impure DNA samples and fail to detect subclones that have different evolutionary trajectories. We have developed a tool, called Treeomics, that allows us to reconstruct the phylogeny of a cancer with commonly available sequencing technologies. Using Bayesian inference and Integer Linear Programming, robust phylogenies consistent with the biological processes underlying cancer evolution were obtained for pancreatic, ovarian, and prostate cancers. Furthermore, Treeomics correctly identified sequencing artifacts such as those resulting from low statistical power; nearly 7% of variants were misclassified by conventional statistical methods. These artifacts can skew phylogenies by creating illusory tumor heterogeneity among distinct samples. Importantly, we show that the evolutionary trees generated with Treeomics are mathematically optimal.
AU - Reiter, Johannes
AU - Makohon-Moore, Alvin
AU - Gerold, Jeffrey
AU - Bozic, Ivana
AU - Chatterjee, Krishnendu
AU - Iacobuzio-Donahue, Christine
AU - Vogelstein, Bert
AU - Nowak, Martin
ID - 5444
SN - 2664-1690
TI - Reconstructing robust phylogenies of metastatic cancers
ER -
TY - DATA
AB - This repository contains the experimental part of the CAV 2015 publication Counterexample Explanation by Learning Small Strategies in Markov Decision Processes.
We extended the probabilistic model checker PRISM to represent strategies of Markov Decision Processes as Decision Trees.
The archive contains a java executable version of the extended tool (prism_dectree.jar) together with a few examples of the PRISM benchmark library.
To execute the program, please have a look at the README.txt, which provides instructions and further information on the archive.
The archive contains scripts that (if run often enough) reproduces the data presented in the publication.
AU - Fellner, Andreas
ID - 5549
KW - Markov Decision Process
KW - Decision Tree
KW - Probabilistic Verification
KW - Counterexample Explanation
TI - Experimental part of CAV 2015 publication: Counterexample Explanation by Learning Small Strategies in Markov Decision Processes
ER -
TY - JOUR
AB - We present here the first integer-based algorithm for constructing a well-defined lattice sphere specified by integer radius and integer center. The algorithm evolves from a unique correspondence between the lattice points comprising the sphere and the distribution of sum of three square numbers in integer intervals. We characterize these intervals to derive a useful set of recurrences, which, in turn, aids in efficient computation. Each point of the lattice sphere is determined by resorting to only a few primitive operations in the integer domain. The symmetry of its quadraginta octants provides an added advantage by confining the computation to its prima quadraginta octant. Detailed theoretical analysis and experimental results have been furnished to demonstrate its simplicity and elegance.
AU - Biswas, Ranita
AU - Bhowmick, Partha
ID - 5804
IS - 4
JF - Theoretical Computer Science
SN - 0304-3975
TI - From prima quadraginta octant to lattice sphere through primitive integer operations
VL - 624
ER -
TY - JOUR
AU - Biswas, Ranita
AU - Bhowmick, Partha
ID - 5807
IS - 11
JF - Theoretical Computer Science
SN - 0304-3975
TI - On different topological classes of spherical geodesic paths and circles inZ3
VL - 605
ER -
TY - JOUR
AU - Biswas, Ranita
AU - Bhowmick, Partha
ID - 5808
IS - 6-8
JF - The Visual Computer
SN - 0178-2789
TI - Layer the sphere
VL - 31
ER -
TY - JOUR
AB - Transcription of eukaryotic protein-coding genes commences with the assembly of a conserved initiation complex, which consists of RNA polymerase II (Pol II) and the general transcription factors, at promoter DNA. After two decades of research, the structural basis of transcription initiation is emerging. Crystal structures of many components of the initiation complex have been resolved, and structural information on Pol II complexes with general transcription factors has recently been obtained. Although mechanistic details await elucidation, available data outline how Pol II cooperates with the general transcription factors to bind to and open promoter DNA, and how Pol II directs RNA synthesis and escapes from the promoter.
AU - Sainsbury, Sarah
AU - Bernecky, Carrie A
AU - Cramer, Patrick
ID - 594
IS - 3
JF - Nature Reviews Molecular Cell Biology
TI - Structural basis of transcription initiation by RNA polymerase II
VL - 16
ER -
TY - JOUR
AB - Carbon dioxide (CO2) gradients are ubiquitous and provide animals with information about their environment, such as the potential presence of prey or predators. The nematode Caenorhabditis elegans avoids elevated CO2, and previous work identified three neuron pairs called “BAG,” “AFD,” and “ASE” that respond to CO2 stimuli. Using in vivo Ca2+ imaging and behavioral analysis, we show that C. elegans can detect CO2 independently of these sensory pathways. Many of the C. elegans sensory neurons we examined, including the AWC olfactory neurons, the ASJ and ASK gustatory neurons, and the ASH and ADL nociceptors, respond to a rise in CO2 with a rise in Ca2+. In contrast, glial sheath cells harboring the sensory endings of C. elegans’ major chemosensory neurons exhibit strong and sustained decreases in Ca2+ in response to high CO2. Some of these CO2 responses appear to be cell intrinsic. Worms therefore may couple detection of CO2 to that of other cues at the earliest stages of sensory processing. We show that C. elegans persistently suppresses oviposition at high CO2. Hermaphrodite-specific neurons (HSNs), the executive neurons driving egg-laying, are tonically inhibited when CO2 is elevated. CO2 modulates the egg-laying system partly through the AWC olfactory neurons: High CO2 tonically activates AWC by a cGMP-dependent mechanism, and AWC output inhibits the HSNs. Our work shows that CO2 is a more complex sensory cue for C. elegans than previously thought, both in terms of behavior and neural circuitry.
AU - Fenk, Lorenz A.
AU - de Bono, Mario
ID - 6118
IS - 27
JF - Proceedings of the National Academy of Sciences
SN - 0027-8424
TI - Environmental CO2 inhibits Caenorhabditis elegans egg-laying by modulating olfactory neurons and evokes widespread changes in neural activity
VL - 112
ER -
TY - JOUR
AB - Brains organize behavior and physiology to optimize the response to threats or opportunities. We dissect how 21% O2, an indicator of surface exposure, reprograms C. elegans' global state, inducing sustained locomotory arousal and altering expression of neuropeptides, metabolic enzymes, and other non-neural genes. The URX O2-sensing neurons drive arousal at 21% O2 by tonically activating the RMG interneurons. Stimulating RMG is sufficient to switch behavioral state. Ablating the ASH, ADL, or ASK sensory neurons connected to RMG by gap junctions does not disrupt arousal. However, disrupting cation currents in these neurons curtails RMG neurosecretion and arousal. RMG signals high O2 by peptidergic secretion. Neuropeptide reporters reveal neural circuit state, as neurosecretion stimulates neuropeptide expression. Neural imaging in unrestrained animals shows that URX and RMG encode O2 concentration rather than behavior, while the activity of downstream interneurons such as AVB and AIY reflect both O2 levels and the behavior being executed.
AU - Laurent, Patrick
AU - Soltesz, Zoltan
AU - Nelson, Geoffrey M
AU - Chen, Changchun
AU - Arellano-Carbajal, Fausto
AU - Levy, Emmanuel
AU - de Bono, Mario
ID - 6120
JF - eLife
SN - 2050-084X
TI - Decoding a neural circuit controlling global animal state in C. elegans
VL - 4
ER -
TY - JOUR
AB - The osteoclast-associated receptor (OSCAR) is a collagen-binding immune receptor with important roles in dendritic cell maturation and activation of inflammatory monocytes as well as in osteoclastogenesis. The crystal structure of the OSCAR ectodomain is presented, both free and in complex with a consensus triple-helical peptide (THP). The structures revealed a collagen-binding site in each immunoglobulin-like domain (D1 and D2). The THP binds near a predicted collagen-binding groove in D1, but a more extensive interaction with D2 is facilitated by the unusually wide D1-D2 interdomain angle in OSCAR. Direct binding assays, combined with site-directed mutagenesis, confirm that the primary collagen-binding site in OSCAR resides in D2, in marked contrast to the related collagen receptors, glycoprotein VI (GPVI) and leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1). Monomeric OSCAR D1D2 binds to the consensus THP with a KD of 28 µM measured in solution, but shows a higher affinity (KD 1.5 μM) when binding to a solid-phase THP, most likely due to an avidity effect. These data suggest a 2-stage model for the interaction of OSCAR with a collagen fibril, with transient, low-affinity interactions initiated by the membrane-distal D1, followed by firm adhesion to the primary binding site in D2.
AU - Zhou, Long
AU - Hinerman, J. M.
AU - Blaszczyk, M.
AU - Miller, J. L. C.
AU - Conrady, D. G.
AU - Barrow, A. D.
AU - Chirgadze, D. Y.
AU - Bihan, D.
AU - Farndale, R. W.
AU - Herr, A. B.
ID - 6507
IS - 5
JF - Blood
SN - 0006-4971
TI - Structural basis for collagen recognition by the immune receptor OSCAR
VL - 127
ER -
TY - JOUR
AB - Motivated by the significant performance gains which polar codes experience under successive cancellation list decoding, their scaling exponent is studied as a function of the list size. In particular, the error probability is fixed, and the tradeoff between the block length and back-off from capacity is analyzed. A lower bound is provided on the error probability under MAP decoding with list size L for any binary-input memoryless output-symmetric channel and for any class of linear codes such that their minimum distance is unbounded as the block length grows large. Then, it is shown that under MAP decoding, although the introduction of a list can significantly improve the involved constants, the scaling exponent itself, i.e., the speed at which capacity is approached, stays unaffected for any finite list size. In particular, this result applies to polar codes, since their minimum distance tends to infinity as the block length increases. A similar result is proved for genie-aided successive cancellation decoding when transmission takes place over the binary erasure channel, namely, the scaling exponent remains constant for any fixed number of helps from the genie. Note that since genie-aided successive cancellation decoding might be strictly worse than successive cancellation list decoding, the problem of establishing the scaling exponent of the latter remains open.
AU - Mondelli, Marco
AU - Hassani, Hamed
AU - Urbanke, Rudiger
ID - 6736
IS - 9
JF - IEEE Transactions on Information Theory
TI - Scaling exponent of list decoders with applications to polar codes
VL - 61
ER -
TY - JOUR
AB - This paper presents polar coding schemes for the two-user discrete memoryless broadcast channel (DM-BC) which achieve Marton's region with both common and private messages. This is the best achievable rate region known to date, and it is tight for all classes of two-user DM-BCs whose capacity regions are known. To accomplish this task, we first construct polar codes for both the superposition as well as binning strategy. By combining these two schemes, we obtain Marton's region with private messages only. Finally, we show how to handle the case of common information. The proposed coding schemes possess the usual advantages of polar codes, i.e., they have low encoding and decoding complexity and a superpolynomial decay rate of the error probability. We follow the lead of Goela, Abbe, and Gastpar, who recently introduced polar codes emulating the superposition and binning schemes. To align the polar indices, for both schemes, their solution involves some degradedness constraints that are assumed to hold between the auxiliary random variables and channel outputs. To remove these constraints, we consider the transmission of k blocks and employ a chaining construction that guarantees the proper alignment of the polarized indices. The techniques described in this paper are quite general, and they can be adopted to many other multiterminal scenarios whenever there polar indices need to be aligned.
AU - Mondelli, Marco
AU - Hassani, Hamed
AU - Sason, Igal
AU - Urbanke, Rudiger
ID - 6737
IS - 2
JF - IEEE Transactions on Information Theory
TI - Achieving Marton’s region for broadcast channels using polar codes
VL - 61
ER -
TY - JOUR
AB - Torque magnetization measurements on YBa2Cu3Oy (YBCO) at doping y=6.67 (p=0.12), in dc fields (B) up to 33 T and temperatures down to 4.5 K, show that weak diamagnetism persists above the extrapolated irreversibility field Hirr(T=0)≈24 T. The differential susceptibility dM/dB, however, is more rapidly suppressed for B≳16 T than expected from the properties of the low field superconducting state, and saturates at a low value for fields B≳24 T. In addition, torque measurements on a p=0.11 YBCO crystal in pulsed field up to 65 T and temperatures down to 8 K show similar behavior, with no additional features at higher fields. We offer two candidate scenarios to explain these observations: (a) superconductivity survives but is heavily suppressed at high field by competition with charge-density-wave (CDW) order; (b) static superconductivity disappears near 24 T and is followed by a region of fluctuating superconductivity, which causes dM/dB to saturate at high field. The diamagnetic signal observed above 50 T for the p=0.11 crystal at 40 K and below may be caused by changes in the normal state susceptibility rather than bulk or fluctuating superconductivity. There will be orbital (Landau) diamagnetism from electron pockets and possibly a reduction in spin susceptibility caused by the stronger three-dimensional ordered CDW.
AU - Yu, Jing Fei
AU - Ramshaw, B. J.
AU - Kokanović, I.
AU - Modic, Kimberly A
AU - Harrison, N.
AU - Day, James
AU - Liang, Ruixing
AU - Hardy, W. N.
AU - Bonn, D. A.
AU - McCollam, A.
AU - Julian, S. R.
AU - Cooper, J. R.
ID - 7070
IS - 18
JF - Physical Review B
SN - 1098-0121
TI - Magnetization of underdoped YBa2Cu3Oy above the irreversibility field
VL - 92
ER -
TY - JOUR
AB - In this paper, we develop an energy method to study finite speed of propagation and waiting time phenomena for the stochastic porous media equation with linear multiplicative noise in up to three spatial dimensions. Based on a novel iteration technique and on stochastic counterparts of weighted integral estimates used in the deterministic setting, we formulate a sufficient criterion on the growth of initial data which locally guarantees a waiting time phenomenon to occur almost surely. Up to a logarithmic factor, this criterion coincides with the optimal criterion known from the deterministic setting. Our technique can be modified to prove finite speed of propagation as well.
AU - Julian Fischer
AU - Grün, Günther
ID - 1311
IS - 1
JF - SIAM Journal on Mathematical Analysis
TI - Finite speed of propagation and waiting times for the stochastic porous medium equation: A unifying approach
VL - 47
ER -
TY - JOUR
AB - We present an algorithm for the derivation of lower bounds on support propagation for a certain class of nonlinear parabolic equations. We proceed by combining the ideas in some recent papers by the author with the algorithmic construction of entropies due to Jüngel and Matthes, reducing the problem to a quantifier elimination problem. Due to its complexity, the quantifier elimination problem cannot be solved by present exact algorithms. However, by tackling the quantifier elimination problem numerically, in the case of the thin-film equation we are able to improve recent results by the author in the regime of strong slippage n ∈ (1, 2). For certain second-order doubly nonlinear parabolic equations, we are able to extend the known lower bounds on free boundary propagation to the case of irregular oscillatory initial data. Finally, we apply our method to a sixth-order quantum drift-diffusion equation, resulting in an upper bound on the time which it takes for the support to reach every point in the domain.
AU - Julian Fischer
ID - 1313
IS - 1
JF - Interfaces and Free Boundaries
TI - Estimates on front propagation for nonlinear higher-order parabolic equations: An algorithmic approach
VL - 17
ER -
TY - JOUR
AB - We derive a posteriori estimates for the modeling error caused by the assumption of perfect incompressibility in the incompressible Navier-Stokes equation: Real fluids are never perfectly incompressible but always feature at least some low amount of compressibility. Thus, their behavior is described by the compressible Navier-Stokes equation, the pressure being a steep function of the density. We rigorously estimate the difference between an approximate solution to the incompressible Navier-Stokes equation and any weak solution to the compressible Navier-Stokes equation in the sense of Lions (without assuming any additional regularity of solutions). Heuristics and numerical results suggest that our error estimates are of optimal order in the case of "well-behaved" flows and divergence-free approximations of the velocity field. Thus, we expect our estimates to justify the idealization of fluids as perfectly incompressible also in practical situations.
AU - Fischer, Julian L
ID - 1314
IS - 5
JF - SIAM Journal on Numerical Analysis
TI - A posteriori modeling error estimates for the assumption of perfect incompressibility in the Navier-Stokes equation
VL - 53
ER -
TY - JOUR
AB - In the present work we introduce the notion of a renormalized solution for reaction–diffusion systems with entropy-dissipating reactions. We establish the global existence of renormalized solutions. In the case of integrable reaction terms our notion of a renormalized solution reduces to the usual notion of a weak solution. Our existence result in particular covers all reaction–diffusion systems involving a single reversible reaction with mass-action kinetics and (possibly species-dependent) Fick-law diffusion; more generally, it covers the case of systems of reversible reactions with mass-action kinetics which satisfy the detailed balance condition. For such equations the existence of any kind of solution in general was an open problem, thereby motivating the study of renormalized solutions.
AU - Julian Fischer
ID - 1316
IS - 1
JF - Archive for Rational Mechanics and Analysis
TI - Global existence of renormalized solutions to entropy-dissipating reaction–diffusion systems
VL - 218
ER -
TY - JOUR
AB - In plants, vacuolar H+-ATPase (V-ATPase) activity acidifies both the trans-Golgi network/early endosome (TGN/EE) and the vacuole. This dual V-ATPase function has impeded our understanding of how the pH homeostasis within the plant TGN/EE controls exo- and endocytosis. Here, we show that the weak V-ATPase mutant deetiolated3 (det3) displayed a pH increase in the TGN/EE, but not in the vacuole, strongly impairing secretion and recycling of the brassinosteroid receptor and the cellulose synthase complexes to the plasma membrane, in contrast to mutants lacking tonoplast-localized V-ATPase activity only. The brassinosteroid insensitivity and the cellulose deficiency defects in det3 were tightly correlated with reduced Golgi and TGN/EE motility. Thus, our results provide strong evidence that acidification of the TGN/EE, but not of the vacuole, is indispensable for functional secretion and recycling in plants.
AU - Yu, Luo
AU - Scholl, Stefan
AU - Doering, Anett
AU - Yi, Zhang
AU - Irani, Niloufer
AU - Di Rubbo, Simone
AU - Neumetzler, Lutz
AU - Krishnamoorthy, Praveen
AU - Van Houtte, Isabelle
AU - Mylle, Evelien
AU - Bischoff, Volker
AU - Vernhettes, Samantha
AU - Winne, Johan
AU - Friml, Jirí
AU - Stierhof, York
AU - Schumacher, Karin
AU - Persson, Staffan
AU - Russinova, Eugenia
ID - 1383
IS - 7
JF - Nature Plants
TI - V-ATPase activity in the TGN/EE is required for exocytosis and recycling in Arabidopsis
VL - 1
ER -
TY - THES
AB - This thesis is concerned with the computation and approximation of intrinsic volumes. Given a smooth body M and a certain digital approximation of it, we develop algorithms to approximate various intrinsic volumes of M using only measurements taken from its digital approximations. The crucial idea behind our novel algorithms is to link the recent theory of persistent homology to the theory of intrinsic volumes via the Crofton formula from integral geometry and, in particular, via Euler characteristic computations. Our main contributions are a multigrid convergent digital algorithm to compute the first intrinsic volume of a solid body in R^n as well as an appropriate integration pipeline to approximate integral-geometric integrals defined over the Grassmannian manifold.
AU - Pausinger, Florian
ID - 1399
TI - On the approximation of intrinsic volumes
ER -
TY - THES
AB - Cancer results from an uncontrolled growth of abnormal cells. Sequentially accumulated genetic and epigenetic alterations decrease cell death and increase cell replication. We used mathematical models to quantify the effect of driver gene mutations. The recently developed targeted therapies can lead to dramatic regressions. However, in solid cancers, clinical responses are often short-lived because resistant cancer cells evolve. We estimated that approximately 50 different mutations can confer resistance to a typical targeted therapeutic agent. We find that resistant cells are likely to be present in expanded subclones before the start of the treatment. The dominant strategy to prevent the evolution of resistance is combination therapy. Our analytical results suggest that in most patients, dual therapy, but not monotherapy, can result in long-term disease control. However, long-term control can only occur if there are no possible mutations in the genome that can cause cross-resistance to both drugs. Furthermore, we showed that simultaneous therapy with two drugs is much more likely to result in long-term disease control than sequential therapy with the same drugs. To improve our understanding of the underlying subclonal evolution we reconstruct the evolutionary history of a patient's cancer from next-generation sequencing data of spatially-distinct DNA samples. Using a quantitative measure of genetic relatedness, we found that pancreatic cancers and their metastases demonstrated a higher level of relatedness than that expected for any two cells randomly taken from a normal tissue. This minimal amount of genetic divergence among advanced lesions indicates that genetic heterogeneity, when quantitatively defined, is not a fundamental feature of the natural history of untreated pancreatic cancers. Our newly developed, phylogenomic tool Treeomics finds evidence for seeding patterns of metastases and can directly be used to discover rules governing the evolution of solid malignancies to transform cancer into a more predictable disease.
AU - Reiter, Johannes
ID - 1400
TI - The subclonal evolution of cancer
ER -
TY - CONF
AB - We consider the problem of statistical computations with persistence diagrams, a summary representation of topological features in data. These diagrams encode persistent homology, a widely used invariant in topological data analysis. While several avenues towards a statistical treatment of the diagrams have been explored recently, we follow an alternative route that is motivated by the success of methods based on the embedding of probability measures into reproducing kernel Hilbert spaces. In fact, a positive definite kernel on persistence diagrams has recently been proposed, connecting persistent homology to popular kernel-based learning techniques such as support vector machines. However, important properties of that kernel enabling a principled use in the context of probability measure embeddings remain to be explored. Our contribution is to close this gap by proving universality of a variant of the original kernel, and to demonstrate its effective use in twosample hypothesis testing on synthetic as well as real-world data.
AU - Kwitt, Roland
AU - Huber, Stefan
AU - Niethammer, Marc
AU - Lin, Weili
AU - Bauer, Ulrich
ID - 1424
TI - Statistical topological data analysis-A kernel perspective
VL - 28
ER -
TY - CONF
AB - In this work we aim at extending the theoretical foundations of lifelong learning. Previous work analyzing this scenario is based on the assumption that learning tasks are sampled i.i.d. from a task environment or limited to strongly constrained data distributions. Instead, we study two scenarios when lifelong learning is possible, even though the observed tasks do not form an i.i.d. sample: first, when they are sampled from the same environment, but possibly with dependencies, and second, when the task environment is allowed to change over time in a consistent way. In the first case we prove a PAC-Bayesian theorem that can be seen as a direct generalization of the analogous previous result for the i.i.d. case. For the second scenario we propose to learn an inductive bias in form of a transfer procedure. We present a generalization bound and show on a toy example how it can be used to identify a beneficial transfer algorithm.
AU - Pentina, Anastasia
AU - Lampert, Christoph
ID - 1425
TI - Lifelong learning with non-i.i.d. tasks
VL - 2015
ER -
TY - CONF
AB - Evolutionary algorithms (EAs) form a popular optimisation paradigm inspired by natural evolution. In recent years the field of evolutionary computation has developed a rigorous analytical theory to analyse their runtime on many illustrative problems. Here we apply this theory to a simple model of natural evolution. In the Strong Selection Weak Mutation (SSWM) evolutionary regime the time between occurrence of new mutations is much longer than the time it takes for a new beneficial mutation to take over the population. In this situation, the population only contains copies of one genotype and evolution can be modelled as a (1+1)-type process where the probability of accepting a new genotype (improvements or worsenings) depends on the change in fitness. We present an initial runtime analysis of SSWM, quantifying its performance for various parameters and investigating differences to the (1+1) EA. We show that SSWM can have a moderate advantage over the (1+1) EA at crossing fitness valleys and study an example where SSWM outperforms the (1+1) EA by taking advantage of information on the fitness gradient.
AU - Paixao, Tiago
AU - Sudholt, Dirk
AU - Heredia, Jorge
AU - Trubenova, Barbora
ID - 1430
T2 - Proceedings of the 2015 Annual Conference on Genetic and Evolutionary Computation
TI - First steps towards a runtime comparison of natural and artificial evolution
ER -
TY - GEN
AB - In this paper we survey geometric and arithmetic techniques to study the cohomology of semiprojective hyperkähler manifolds including toric hyperkähler varieties, Nakajima quiver varieties and moduli spaces of Higgs bundles on Riemann surfaces. The resulting formulae for their Poincaré polynomials are combinatorial and representation theoretical in nature. In particular we will look at their Betti numbers and will establish some results and state some expectations on their asymptotic shape.
AU - Tamas Hausel
AU - Rodríguez Villegas, Fernando
ID - 1473
IS - 370
T2 - Asterisque
TI - Cohomology of large semiprojective hyperkähler varieties
VL - 2015
ER -
TY - CONF
AB - Cryptographic access control offers selective access to encrypted data via a combination of key management and functionality-rich cryptographic schemes, such as attribute-based encryption. Using this approach, publicly available meta-data may inadvertently leak information on the access policy that is enforced by cryptography, which renders cryptographic access control unusable in settings where this information is highly sensitive. We begin to address this problem by presenting rigorous definitions for policy privacy in cryptographic access control. For concreteness we set our results in the model of Role-Based Access Control (RBAC), where we identify and formalize several different flavors of privacy, however, our framework should serve as inspiration for other models of access control. Based on our insights we propose a new system which significantly improves on the privacy properties of state-of-the-art constructions. Our design is based on a novel type of privacy-preserving attribute-based encryption, which we introduce and show how to instantiate. We present our results in the context of a cryptographic RBAC system by Ferrara et al. (CSF'13), which uses cryptography to control read access to files, while write access is still delegated to trusted monitors. We give an extension of the construction that permits cryptographic control over write access. Our construction assumes that key management uses out-of-band channels between the policy enforcer and the users but eliminates completely the need for monitoring read/write access to the data.
AU - Ferrara, Anna
AU - Fuchsbauer, Georg
AU - Liu, Bin
AU - Warinschi, Bogdan
ID - 1474
TI - Policy privacy in cryptographic access control
ER -
TY - CONF
AB - Simple board games, like Tic-Tac-Toe and CONNECT-4, play an important role not only in the development of mathematical and logical skills, but also in the emotional and social development. In this paper, we address the problem of generating targeted starting positions for such games. This can facilitate new approaches for bringing novice players to mastery, and also leads to discovery of interesting game variants. We present an approach that generates starting states of varying hardness levels for player 1 in a two-player board game, given rules of the board game, the desired number of steps required for player 1 to win, and the expertise levels of the two players. Our approach leverages symbolic methods and iterative simulation to efficiently search the extremely large state space. We present experimental results that include discovery of states of varying hardness levels for several simple grid-based board games. The presence of such states for standard game variants like 4×4 Tic-Tac-Toe opens up new games to be played that have never been played as the default start state is heavily biased.
AU - Ahmed, Umair
AU - Chatterjee, Krishnendu
AU - Gulwani, Sumit
ID - 1481
T2 - Proceedings of the Twenty-Ninth AAAI Conference on Artificial Intelligence
TI - Automatic generation of alternative starting positions for simple traditional board games
VL - 2
ER -
TY - CONF
AB - Topological data analysis offers a rich source of valuable information to study vision problems. Yet, so far we lack a theoretically sound connection to popular kernel-based learning techniques, such as kernel SVMs or kernel PCA. In this work, we establish such a connection by designing a multi-scale kernel for persistence diagrams, a stable summary representation of topological features in data. We show that this kernel is positive definite and prove its stability with respect to the 1-Wasserstein distance. Experiments on two benchmark datasets for 3D shape classification/retrieval and texture recognition show considerable performance gains of the proposed method compared to an alternative approach that is based on the recently introduced persistence landscapes.
AU - Reininghaus, Jan
AU - Huber, Stefan
AU - Bauer, Ulrich
AU - Kwitt, Roland
ID - 1483
TI - A stable multi-scale kernel for topological machine learning
ER -
TY - CONF
AB - Motivated by biological questions, we study configurations of equal-sized disks in the Euclidean plane that neither pack nor cover. Measuring the quality by the probability that a random point lies in exactly one disk, we show that the regular hexagonal grid gives the maximum among lattice configurations.
AU - Edelsbrunner, Herbert
AU - Iglesias Ham, Mabel
AU - Kurlin, Vitaliy
ID - 1495
T2 - Proceedings of the 27th Canadian Conference on Computational Geometry
TI - Relaxed disk packing
VL - 2015-August
ER -
TY - JOUR
AB - Detecting allelic biases from high-throughput sequencing data requires an approach that maximises sensitivity while minimizing false positives. Here, we present Allelome.PRO, an automated user-friendly bioinformatics pipeline, which uses high-throughput sequencing data from reciprocal crosses of two genetically distinct mouse strains to detect allele-specific expression and chromatin modifications. Allelome.PRO extends approaches used in previous studies that exclusively analyzed imprinted expression to give a complete picture of the ‘allelome’ by automatically categorising the allelic expression of all genes in a given cell type into imprinted, strain-biased, biallelic or non-informative. Allelome.PRO offers increased sensitivity to analyze lowly expressed transcripts, together with a robust false discovery rate empirically calculated from variation in the sequencing data. We used RNA-seq data from mouse embryonic fibroblasts from F1 reciprocal crosses to determine a biologically relevant allelic ratio cutoff, and define for the first time an entire allelome. Furthermore, we show that Allelome.PRO detects differential enrichment of H3K4me3 over promoters from ChIP-seq data validating the RNA-seq results. This approach can be easily extended to analyze histone marks of active enhancers, or transcription factor binding sites and therefore provides a powerful tool to identify candidate cis regulatory elements genome wide.
AU - Andergassen, Daniel
AU - Dotter, Christoph
AU - Kulinski, Tomasz
AU - Guenzl, Philipp
AU - Bammer, Philipp
AU - Barlow, Denise
AU - Pauler, Florian
AU - Hudson, Quanah
ID - 1497
IS - 21
JF - Nucleic Acids Research
TI - Allelome.PRO, a pipeline to define allele-specific genomic features from high-throughput sequencing data
VL - 43
ER -
TY - CONF
AB - Fault-tolerant distributed algorithms play an important role in many critical/high-availability applications. These algorithms are notoriously difficult to implement correctly, due to asynchronous communication and the occurrence of faults, such as the network dropping messages or computers crashing. Nonetheless there is surprisingly little language and verification support to build distributed systems based on fault-tolerant algorithms. In this paper, we present some of the challenges that a designer has to overcome to implement a fault-tolerant distributed system. Then we review different models that have been proposed to reason about distributed algorithms and sketch how such a model can form the basis for a domain-specific programming language. Adopting a high-level programming model can simplify the programmer's life and make the code amenable to automated verification, while still compiling to efficiently executable code. We conclude by summarizing the current status of an ongoing language design and implementation project that is based on this idea.
AU - Dragoi, Cezara
AU - Henzinger, Thomas A
AU - Zufferey, Damien
ID - 1498
SN - 978-3-939897-80-4
TI - The need for language support for fault-tolerant distributed systems
VL - 32
ER -
TY - CONF
AB - We consider weighted automata with both positive and negative integer weights on edges and
study the problem of synchronization using adaptive strategies that may only observe whether
the current weight-level is negative or nonnegative. We show that the synchronization problem is decidable in polynomial time for deterministic weighted automata.
AU - Kretinsky, Jan
AU - Larsen, Kim
AU - Laursen, Simon
AU - Srba, Jiří
ID - 1499
TI - Polynomial time decidability of weighted synchronization under partial observability
VL - 42
ER -
TY - GEN
AB - In this poster, we present methods for randomly generating hybrid automata with affine differential equations, invariants, guards, and assignments. Selecting an arbitrary affine function from the set of all affine functions results in a low likelihood of generating hybrid automata with diverse and interesting behaviors, as there are an uncountable number of elements in the set of all affine functions. Instead, we partition the set of all affine functions into potentially interesting classes and randomly select elements from these classes. For example, we partition the set of all affine differential equations by using restrictions on eigenvalues such as those that yield stable, unstable, etc. equilibrium points. We partition the components describing discrete behavior (guards, assignments, and invariants) to allow either time-dependent or state-dependent switching, and in particular provide the ability to generate subclasses of piecewise-affine hybrid automata. Our preliminary experimental results with a prototype tool called HyRG (Hybrid Random Generator) illustrate the feasibility of this generation method to automatically create standard hybrid automaton examples like the bouncing ball and thermostat.
AU - Nguyen, Luan V
AU - Christian Schilling
AU - Sergiy Bogomolov
AU - Johnson, Taylor T
ID - 1500
T2 - HSCC: Hybrid Systems - Computation and Control
TI - Poster: HyRG: A random generation tool for affine hybrid automata
ER -
TY - JOUR
AB - We consider Markov decision processes (MDPs) which are a standard model for probabilistic systems. We focus on qualitative properties for MDPs that can express that desired behaviors of the system arise almost-surely (with probability 1) or with positive probability. We introduce a new simulation relation to capture the refinement relation of MDPs with respect to qualitative properties, and present discrete graph algorithms with quadratic complexity to compute the simulation relation. We present an automated technique for assume-guarantee style reasoning for compositional analysis of two-player games by giving a counterexample guided abstraction-refinement approach to compute our new simulation relation. We show a tight link between two-player games and MDPs, and as a consequence the results for games are lifted to MDPs with qualitative properties. We have implemented our algorithms and show that the compositional analysis leads to significant improvements.
AU - Chatterjee, Krishnendu
AU - Chmelik, Martin
AU - Daca, Przemyslaw
ID - 1501
IS - 2
JF - Formal Methods in System Design
TI - CEGAR for compositional analysis of qualitative properties in Markov decision processes
VL - 47
ER -
TY - CONF
AB - We extend the theory of input-output conformance with operators for merge and quotient. The former is useful when testing against multiple requirements or views. The latter can be used to generate tests for patches of an already tested system. Both operators can combine systems with different action alphabets, which is usually the case when constructing complex systems and specifications from parts, for instance different views as well as newly defined functionality of a~previous version of the system.
AU - Beneš, Nikola
AU - Daca, Przemyslaw
AU - Henzinger, Thomas A
AU - Kretinsky, Jan
AU - Nickovic, Dejan
ID - 1502
SN - 978-1-4503-3471-6
TI - Complete composition operators for IOCO-testing theory
ER -
TY - JOUR
AB - A Herman-Avila-Bochi type formula is obtained for the average sum of the top d Lyapunov exponents over a one-parameter family of double-struck G-cocycles, where double-struck G is the group that leaves a certain, non-degenerate Hermitian form of signature (c, d) invariant. The generic example of such a group is the pseudo-unitary group U(c, d) or, in the case c = d, the Hermitian-symplectic group HSp(2d) which naturally appears for cocycles related to Schrödinger operators. In the case d = 1, the formula for HSp(2d) cocycles reduces to the Herman-Avila-Bochi formula for SL(2, ℝ) cocycles.
AU - Sadel, Christian
ID - 1503
IS - 5
JF - Ergodic Theory and Dynamical Systems
TI - A Herman-Avila-Bochi formula for higher-dimensional pseudo-unitary and Hermitian-symplectic-cocycles
VL - 35
ER -
TY - JOUR
AB - Let Q = (Q1, . . . , Qn) be a random vector drawn from the uniform distribution on the set of all n! permutations of {1, 2, . . . , n}. Let Z = (Z1, . . . , Zn), where Zj is the mean zero variance one random variable obtained by centralizing and normalizing Qj , j = 1, . . . , n. Assume that Xi , i = 1, . . . ,p are i.i.d. copies of 1/√ p Z and X = Xp,n is the p × n random matrix with Xi as its ith row. Then Sn = XX is called the p × n Spearman's rank correlation matrix which can be regarded as a high dimensional extension of the classical nonparametric statistic Spearman's rank correlation coefficient between two independent random variables. In this paper, we establish a CLT for the linear spectral statistics of this nonparametric random matrix model in the scenario of high dimension, namely, p = p(n) and p/n→c ∈ (0,∞) as n→∞.We propose a novel evaluation scheme to estimate the core quantity in Anderson and Zeitouni's cumulant method in [Ann. Statist. 36 (2008) 2553-2576] to bypass the so-called joint cumulant summability. In addition, we raise a two-step comparison approach to obtain the explicit formulae for the mean and covariance functions in the CLT. Relying on this CLT, we then construct a distribution-free statistic to test complete independence for components of random vectors. Owing to the nonparametric property, we can use this test on generally distributed random variables including the heavy-tailed ones.
AU - Bao, Zhigang
AU - Lin, Liang
AU - Pan, Guangming
AU - Zhou, Wang
ID - 1504
IS - 6
JF - Annals of Statistics
TI - Spectral statistics of large dimensional spearman s rank correlation matrix and its application
VL - 43
ER -
TY - JOUR
AB - This paper is aimed at deriving the universality of the largest eigenvalue of a class of high-dimensional real or complex sample covariance matrices of the form W N =Σ 1/2XX∗Σ 1/2 . Here, X = (xij )M,N is an M× N random matrix with independent entries xij , 1 ≤ i M,≤ 1 ≤ j ≤ N such that Exij = 0, E|xij |2 = 1/N . On dimensionality, we assume that M = M(N) and N/M → d ε (0, ∞) as N ∞→. For a class of general deterministic positive-definite M × M matrices Σ , under some additional assumptions on the distribution of xij 's, we show that the limiting behavior of the largest eigenvalue of W N is universal, via pursuing a Green function comparison strategy raised in [Probab. Theory Related Fields 154 (2012) 341-407, Adv. Math. 229 (2012) 1435-1515] by Erd″os, Yau and Yin for Wigner matrices and extended by Pillai and Yin [Ann. Appl. Probab. 24 (2014) 935-1001] to sample covariance matrices in the null case (&Epsi = I ). Consequently, in the standard complex case (Ex2 ij = 0), combing this universality property and the results known for Gaussian matrices obtained by El Karoui in [Ann. Probab. 35 (2007) 663-714] (nonsingular case) and Onatski in [Ann. Appl. Probab. 18 (2008) 470-490] (singular case), we show that after an appropriate normalization the largest eigenvalue of W N converges weakly to the type 2 Tracy-Widom distribution TW2 . Moreover, in the real case, we show that whenΣ is spiked with a fixed number of subcritical spikes, the type 1 Tracy-Widom limit TW1 holds for the normalized largest eigenvalue of W N , which extends a result of Féral and Péché in [J. Math. Phys. 50 (2009) 073302] to the scenario of nondiagonal Σ and more generally distributed X . In summary, we establish the Tracy-Widom type universality for the largest eigenvalue of generally distributed sample covariance matrices under quite light assumptions on &Sigma . Applications of these limiting results to statistical signal detection and structure recognition of separable covariance matrices are also discussed.
AU - Bao, Zhigang
AU - Pan, Guangming
AU - Zhou, Wang
ID - 1505
IS - 1
JF - Annals of Statistics
TI - Universality for the largest eigenvalue of sample covariance matrices with general population
VL - 43
ER -
TY - JOUR
AB - Consider the square random matrix An = (aij)n,n, where {aij:= a(n)ij , i, j = 1, . . . , n} is a collection of independent real random variables with means zero and variances one. Under the additional moment condition supn max1≤i,j ≤n Ea4ij <∞, we prove Girko's logarithmic law of det An in the sense that as n→∞ log | detAn| ? (1/2) log(n-1)! d/→√(1/2) log n N(0, 1).
AU - Bao, Zhigang
AU - Pan, Guangming
AU - Zhou, Wang
ID - 1506
IS - 3
JF - Bernoulli
TI - The logarithmic law of random determinant
VL - 21
ER -
TY - JOUR
AB - We consider generalized Wigner ensembles and general β-ensembles with analytic potentials for any β ≥ 1. The recent universality results in particular assert that the local averages of consecutive eigenvalue gaps in the bulk of the spectrum are universal in the sense that they coincide with those of the corresponding Gaussian β-ensembles. In this article, we show that local averaging is not necessary for this result, i.e. we prove that the single gap distributions in the bulk are universal. In fact, with an additional step, our result can be extended to any C4(ℝ) potential.
AU - Erdös, László
AU - Yau, Horng
ID - 1508
IS - 8
JF - Journal of the European Mathematical Society
TI - Gap universality of generalized Wigner and β ensembles
VL - 17
ER -
TY - JOUR
AB - The Auxin Binding Protein1 (ABP1) has been identified based on its ability to bind auxin with high affinity and studied for a long time as a prime candidate for the extracellular auxin receptor responsible for mediating in particular the fast non-transcriptional auxin responses. However, the contradiction between the embryo-lethal phenotypes of the originally described Arabidopsis T-DNA insertional knock-out alleles (abp1-1 and abp1-1s) and the wild type-like phenotypes of other recently described loss-of-function alleles (abp1-c1 and abp1-TD1) questions the biological importance of ABP1 and relevance of the previous genetic studies. Here we show that there is no hidden copy of the ABP1 gene in the Arabidopsis genome but the embryo-lethal phenotypes of abp1-1 and abp1-1s alleles are very similar to the knock-out phenotypes of the neighboring gene, BELAYA SMERT (BSM). Furthermore, the allelic complementation test between bsm and abp1 alleles shows that the embryo-lethality in the abp1-1 and abp1-1s alleles is caused by the off-target disruption of the BSM locus by the T-DNA insertions. This clarifies the controversy of different phenotypes among published abp1 knock-out alleles and asks for reflections on the developmental role of ABP1.
AU - Michalko, Jaroslav
AU - Dravecka, Marta
AU - Bollenbach, Tobias
AU - Friml, Jirí
ID - 1509
JF - F1000 Research
TI - Embryo-lethal phenotypes in early abp1 mutants are due to disruption of the neighboring BSM gene
VL - 4
ER -
TY - CONF
AB - The concept of well group in a special but important case captures homological properties of the zero set of a continuous map f from K to R^n on a compact space K that are invariant with respect to perturbations of f. The perturbations are arbitrary continuous maps within L_infty distance r from f for a given r > 0. The main drawback of the approach is that the computability of well groups was shown only when dim K = n or n = 1. Our contribution to the theory of well groups is twofold: on the one hand we improve on the computability issue, but on the other hand we present a range of examples where the well groups are incomplete invariants, that is, fail to capture certain important robust properties of the zero set. For the first part, we identify a computable subgroup of the well group that is obtained by cap product with the pullback of the orientation of R^n by f. In other words, well groups can be algorithmically approximated from below. When f is smooth and dim K < 2n-2, our approximation of the (dim K-n)th well group is exact. For the second part, we find examples of maps f, f' from K to R^n with all well groups isomorphic but whose perturbations have different zero sets. We discuss on a possible replacement of the well groups of vector valued maps by an invariant of a better descriptive power and computability status.
AU - Franek, Peter
AU - Krcál, Marek
ID - 1510
TI - On computability and triviality of well groups
VL - 34
ER -
TY - CONF
AB - The fact that the complete graph K_5 does not embed in the plane has been generalized in two independent directions. On the one hand, the solution of the classical Heawood problem for graphs on surfaces established that the complete graph K_n embeds in a closed surface M if and only if (n-3)(n-4) is at most 6b_1(M), where b_1(M) is the first Z_2-Betti number of M. On the other hand, Van Kampen and Flores proved that the k-skeleton of the n-dimensional simplex (the higher-dimensional analogue of K_{n+1}) embeds in R^{2k} if and only if n is less or equal to 2k+2. Two decades ago, Kuhnel conjectured that the k-skeleton of the n-simplex embeds in a compact, (k-1)-connected 2k-manifold with kth Z_2-Betti number b_k only if the following generalized Heawood inequality holds: binom{n-k-1}{k+1} is at most binom{2k+1}{k+1} b_k. This is a common generalization of the case of graphs on surfaces as well as the Van Kampen--Flores theorem. In the spirit of Kuhnel's conjecture, we prove that if the k-skeleton of the n-simplex embeds in a 2k-manifold with kth Z_2-Betti number b_k, then n is at most 2b_k binom{2k+2}{k} + 2k + 5. This bound is weaker than the generalized Heawood inequality, but does not require the assumption that M is (k-1)-connected. Our proof uses a result of Volovikov about maps that satisfy a certain homological triviality condition.
AU - Goaoc, Xavier
AU - Mabillard, Isaac
AU - Paták, Pavel
AU - Patakova, Zuzana
AU - Tancer, Martin
AU - Wagner, Uli
ID - 1511
TI - On generalized Heawood inequalities for manifolds: A Van Kampen–Flores-type nonembeddability result
VL - 34
ER -
TY - CONF
AB - We show that very weak topological assumptions are enough to ensure the existence of a Helly-type theorem. More precisely, we show that for any non-negative integers b and d there exists an integer h(b,d) such that the following holds. If F is a finite family of subsets of R^d such that the ith reduced Betti number (with Z_2 coefficients in singular homology) of the intersection of any proper subfamily G of F is at most b for every non-negative integer i less or equal to (d-1)/2, then F has Helly number at most h(b,d). These topological conditions are sharp: not controlling any of these first Betti numbers allow for families with unbounded Helly number. Our proofs combine homological non-embeddability results with a Ramsey-based approach to build, given an arbitrary simplicial complex K, some well-behaved chain map from C_*(K) to C_*(R^d). Both techniques are of independent interest.
AU - Goaoc, Xavier
AU - Paták, Pavel
AU - Patakova, Zuzana
AU - Tancer, Martin
AU - Wagner, Uli
ID - 1512
TI - Bounding Helly numbers via Betti numbers
VL - 34
ER -
TY - JOUR
AB - Insects of the order Hemiptera (true bugs) use a wide range of mechanisms of sex determination, including genetic sex determination, paternal genome elimination, and haplodiploidy. Genetic sex determination, the prevalent mode, is generally controlled by a pair of XY sex chromosomes or by an XX/X0 system, but different configurations that include additional sex chromosomes are also present. Although this diversity of sex determining systems has been extensively studied at the cytogenetic level, only the X chromosome of the model pea aphid Acyrthosiphon pisum has been analyzed at the genomic level, and little is known about X chromosome biology in the rest of the order.
In this study, we take advantage of published DNA- and RNA-seq data from three additional Hemiptera species to perform a comparative analysis of the gene content and expression of the X chromosome throughout this clade. We find that, despite showing evidence of dosage compensation, the X chromosomes of these species show female-biased expression, and a deficit of male-biased genes, in direct contrast to the pea aphid X. We further detect an excess of shared gene content between these very distant species, suggesting that despite the diversity of sex determining systems, the same chromosomal element is used as the X throughout a large portion of the order.
AU - Pal, Arka
AU - Vicoso, Beatriz
ID - 1513
IS - 12
JF - Genome Biology and Evolution
TI - The X chromosome of hemipteran insects: Conservation, dosage compensation and sex-biased expression
VL - 7
ER -
TY - JOUR
AB - Endocannabinoids (eCBs) play key roles in brain function, acting as modulatory signals in synaptic transmission and plasticity. They are recognized as retrograde messengers that mediate long-term synaptic depression (LTD), but their ability to induce long-term potentiation (LTP) is poorly known. We show that eCBs induce the long-term enhancement of transmitter release at single hippocampal synapses through stimulation of astrocytes when coincident with postsynaptic activity. This LTP requires the coordinated activity of the 3 elements of the tripartite synapse: 1) eCB-evoked astrocyte calcium signal that stimulates glutamate release; 2) postsynaptic nitric oxide production; and 3) activation of protein kinase C and presynaptic group I metabotropic glutamate receptors, whose location at presynaptic sites was confirmed by immunoelectron microscopy. Hence, while eCBs act as retrograde signals to depress homoneuronal synapses, they serve as lateral messengers to induce LTP in distant heteroneuronal synapses through stimulation of astrocytes. Therefore, eCBs can trigger LTP through stimulation of astrocyte-neuron signaling, revealing novel cellular mechanisms of eCB effects on synaptic plasticity.
AU - Gómez-Gonzalo, Marta
AU - Navarrete, Marta
AU - Perea, Gertrudis
AU - Covelo, Ana
AU - Martín-Fernández, Mario
AU - Ryuichi Shigemoto
AU - Luján, Rafael
AU - Araque, Alfonso
ID - 1514
IS - 10
JF - Cerebral Cortex
TI - Endocannabinoids induce lateral long term potentiation of transmitter release by stimulation of gliotransmission
VL - 25
ER -
TY - JOUR
AB - Type 1 metabotropic glutamate (mGlu1) receptors play a pivotal role in different forms of synaptic plasticity in the cerebellar cortex, e.g. long-term depression at glutamatergic synapses and rebound potentiation at GABAergic synapses. These various forms of plasticity might depend on the subsynaptic arrangement of the receptor in Purkinje cells that can be regulated by protein-protein interactions. This study investigated, by means of the freeze-fracture replica immunogold labelling method, the subcellular localization of mGlu1 receptors in the rodent cerebellum and whether Homer proteins regulate their subsynaptic distribution. We observed a widespread extrasynaptic localization of mGlu1 receptors and confirmed their peri-synaptic enrichment at glutamatergic synapses. Conversely, we detected mGlu1 receptors within the main body of GABAergic synapses onto Purkinje cell dendrites. Although Homer proteins are known to interact with the mGlu1 receptor C-terminus, we could not detect Homer3, the most abundant Homer protein in the cerebellar cortex, at GABAergic synapses by pre-embedding and post-embedding immunoelectron microscopy. We then hypothesized a critical role for Homer proteins in the peri-junctional localization of mGlu1 receptors at glutamatergic synapses. To disrupt Homer-associated protein complexes, mice were tail-vein injected with the membrane-permeable dominant-negative TAT-Homer1a. Freeze-fracture replica immunogold labelling analysis showed no significant alteration in the mGlu1 receptor distribution pattern at parallel fibre-Purkinje cell synapses, suggesting that other scaffolding proteins are involved in the peri-synaptic confinement. The identification of interactors that regulate the subsynaptic localization of the mGlu1 receptor at neurochemically distinct synapses may offer new insight into its trafficking and intracellular signalling.
AU - Mansouri, Mahnaz
AU - Kasugai, Yu
AU - Fukazawa, Yugo
AU - Bertaso, Federica
AU - Raynaud, Fabrice
AU - Perroy, Julie
AU - Fagni, Laurent
AU - Walter Kaufmann
AU - Watanabe, Masahiko
AU - Ryuichi Shigemoto
AU - Ferraguti, Francesco
ID - 1515
IS - 2
JF - European Journal of Neuroscience
TI - Distinct subsynaptic localization of type 1 metabotropic glutamate receptors at glutamatergic and GABAergic synapses in the rodent cerebellar cortex
VL - 41
ER -
TY - JOUR
AB - We study the large deviation rate functional for the empirical distribution of independent Brownian particles with drift. In one dimension, it has been shown by Adams, Dirr, Peletier and Zimmer that this functional is asymptotically equivalent (in the sense of Γ-convergence) to the Jordan-Kinderlehrer-Otto functional arising in the Wasserstein gradient flow structure of the Fokker-Planck equation. In higher dimensions, part of this statement (the lower bound) has been recently proved by Duong, Laschos and Renger, but the upper bound remained open, since the proof of Duong et al relies on regularity properties of optimal transport maps that are restricted to one dimension. In this note we present a new proof of the upper bound, thereby generalising the result of Adams et al to arbitrary dimensions.
AU - Erbar, Matthias
AU - Maas, Jan
AU - Renger, Michiel
ID - 1517
JF - Electronic Communications in Probability
TI - From large deviations to Wasserstein gradient flows in multiple dimensions
VL - 20
ER -
TY - JOUR
AB - Evolutionary biologists have an array of powerful theoretical techniques that can accurately predict changes in the genetic composition of populations. Changes in gene frequencies and genetic associations between loci can be tracked as they respond to a wide variety of evolutionary forces. However, it is often less clear how to decompose these various forces into components that accurately reflect the underlying biology. Here, we present several issues that arise in the definition and interpretation of selection and selection coefficients, focusing on insights gained through the examination of selection coefficients in multilocus notation. Using this notation, we discuss how its flexibility-which allows different biological units to be identified as targets of selection-is reflected in the interpretation of the coefficients that the notation generates. In many situations, it can be difficult to agree on whether loci can be considered to be under "direct" versus "indirect" selection, or to quantify this selection. We present arguments for what the terms direct and indirect selection might best encompass, considering a range of issues, from viability and sexual selection to kin selection. We show how multilocus notation can discriminate between direct and indirect selection, and describe when it can do so.
AU - Barton, Nicholas H
AU - Servedio, Maria
ID - 1519
IS - 5
JF - Evolution
TI - The interpretation of selection coefficients
VL - 69
ER -
TY - CONF
AB - Creating mechanical automata that can walk in stable and pleasing manners is a challenging task that requires both skill and expertise. We propose to use computational design to offset the technical difficulties of this process. A simple drag-and-drop interface allows casual users to create personalized walking toys from a library of pre-defined template mechanisms. Provided with this input, our method leverages physical simulation and evolutionary optimization to refine the mechanical designs such that the resulting toys are able to walk. The optimization process is guided by an intuitive set of objectives that measure the quality of the walking motions. We demonstrate our approach on a set of simulated mechanical toys with different numbers of legs and various distinct gaits. Two fabricated prototypes showcase the feasibility of our designs.
AU - Bharaj, Gaurav
AU - Coros, Stelian
AU - Thomaszewski, Bernhard
AU - Tompkin, James
AU - Bickel, Bernd
AU - Pfister, Hanspeter
ID - 1520
SN - 978-1-4503-3496-9
TI - Computational design of walking automata
ER -
TY - JOUR
AB - Based on 16 recommendations, efforts should be made to achieve the following goal: By 2025, all scholarly publication activity in Austria should be Open Access. In other words, the final versions of all scholarly publications resulting from the support of public resources must be freely accessible on the Internet without delay (Gold Open Access). The resources required to meet this obligation shall be provided to the authors, or the cost of the publication venues shall be borne directly by the research organisations.
AU - Bauer, Bruno
AU - Blechl, Guido
AU - Bock, Christoph
AU - Danowski, Patrick
AU - Ferus, Andreas
AU - Graschopf, Anton
AU - König, Thomas
AU - Mayer, Katja
AU - Reckling, Falk
AU - Rieck, Katharina
AU - Seitz, Peter
AU - Stöger, Herwig
AU - Welzig, Elvira
ID - 1525
IS - 3
JF - VÖB Mitteilungen
TI - Arbeitsgruppe „Nationale Strategie“ des Open Access Network Austria OANA
VL - 68
ER -
TY - JOUR
AB - In growing cells, protein synthesis and cell growth are typically not synchronous, and, thus, protein concentrations vary over the cell division cycle. We have developed a theoretical description of genetic regulatory systems in bacteria that explicitly considers the cell division cycle to investigate its impact on gene expression. We calculate the cell-to-cell variations arising from cells being at different stages in the division cycle for unregulated genes and for basic regulatory mechanisms. These variations contribute to the extrinsic noise observed in single-cell experiments, and are most significant for proteins with short lifetimes. Negative autoregulation buffers against variation of protein concentration over the division cycle, but the effect is found to be relatively weak. Stronger buffering is achieved by an increased protein lifetime. Positive autoregulation can strongly amplify such variation if the parameters are set to values that lead to resonance-like behaviour. For cooperative positive autoregulation, the concentration variation over the division cycle diminishes the parameter region of bistability and modulates the switching times between the two stable states. The same effects are seen for a two-gene mutual-repression toggle switch. By contrast, an oscillatory circuit, the repressilator, is only weakly affected by the division cycle.
AU - Bierbaum, Veronika
AU - Klumpp, Stefan
ID - 1530
IS - 6
JF - Physical Biology
TI - Impact of the cell division cycle on gene circuits
VL - 12
ER -
TY - JOUR
AB - The Heat Kernel Signature (HKS) is a scalar quantity which is derived from the heat kernel of a given shape. Due to its robustness, isometry invariance, and multiscale nature, it has been successfully applied in many geometric applications. From a more general point of view, the HKS can be considered as a descriptor of the metric of a Riemannian manifold. Given a symmetric positive definite tensor field we may interpret it as the metric of some Riemannian manifold and thereby apply the HKS to visualize and analyze the given tensor data. In this paper, we propose a generalization of this approach that enables the treatment of indefinite tensor fields, like the stress tensor, by interpreting them as a generator of a positive definite tensor field. To investigate the usefulness of this approach we consider the stress tensor from the two-point-load model example and from a mechanical work piece.
AU - Zobel, Valentin
AU - Jan Reininghaus
AU - Hotz, Ingrid
ID - 1531
JF - Mathematics and Visualization
TI - Visualizing symmetric indefinite 2D tensor fields using The Heat Kernel Signature
VL - 40
ER -
TY - JOUR
AB - This paper addresses the problem of semantic segmentation, where the possible class labels are from a predefined set. We exploit top-down guidance, i.e., the coarse localization of the objects and their class labels provided by object detectors. For each detected bounding box, figure-ground segmentation is performed and the final result is achieved by merging the figure-ground segmentations. The main idea of the proposed approach, which is presented in our preliminary work, is to reformulate the figure-ground segmentation problem as sparse reconstruction pursuing the object mask in a nonparametric manner. The latent segmentation mask should be coherent subject to sparse error caused by intra-category diversity; thus, the object mask is inferred by making use of sparse representations over the training set. To handle local spatial deformations, local patch-level masks are also considered and inferred by sparse representations over the spatially nearby patches. The sparse reconstruction coefficients and the latent mask are alternately optimized by applying the Lasso algorithm and the accelerated proximal gradient method. The proposed formulation results in a convex optimization problem; thus, the global optimal solution is achieved. In this paper, we provide theoretical analysis of the convergence and optimality. We also give an extended numerical analysis of the proposed algorithm and a comprehensive comparison with the related semantic segmentation methods on the challenging PASCAL visual object class object segmentation datasets and the Weizmann horse dataset. The experimental results demonstrate that the proposed algorithm achieves a competitive performance when compared with the state of the arts.
AU - Xia, Wei
AU - Domokos, Csaba
AU - Xiong, Junjun
AU - Cheong, Loongfah
AU - Yan, Shuicheng
ID - 1533
IS - 8
JF - IEEE Transactions on Circuits and Systems for Video Technology
TI - Segmentation over detection via optimal sparse reconstructions
VL - 25
ER -
TY - JOUR
AB - PIN proteins are auxin export carriers that direct intercellular auxin flow and in turn regulate many aspects of plant growth and development including responses to environmental changes. The Arabidopsis R2R3-MYB transcription factor FOUR LIPS (FLP) and its paralogue MYB88 regulate terminal divisions during stomatal development, as well as female reproductive development and stress responses. Here we show that FLP and MYB88 act redundantly but differentially in regulating the transcription of PIN3 and PIN7 in gravity-sensing cells of primary and lateral roots. On the one hand, FLP is involved in responses to gravity stimulation in primary roots, whereas on the other, FLP and MYB88 function complementarily in establishing the gravitropic set-point angles of lateral roots. Our results support a model in which FLP and MYB88 expression specifically determines the temporal-spatial patterns of PIN3 and PIN7 transcription that are closely associated with their preferential functions during root responses to gravity.
AU - Wang, Hongzhe
AU - Yang, Kezhen
AU - Zou, Junjie
AU - Zhu, Lingling
AU - Xie, Zidian
AU - Morita, Miyoterao
AU - Tasaka, Masao
AU - Friml, Jirí
AU - Grotewold, Erich
AU - Beeckman, Tom
AU - Vanneste, Steffen
AU - Sack, Fred
AU - Le, Jie
ID - 1534
JF - Nature Communications
TI - Transcriptional regulation of PIN genes by FOUR LIPS and MYB88 during Arabidopsis root gravitropism
VL - 6
ER -
TY - JOUR
AB - Neuronal and neuroendocrine L-type calcium channels (Cav1.2, Cav1.3) open readily at relatively low membrane potentials and allow Ca2+ to enter the cells near resting potentials. In this way, Cav1.2 and Cav1.3 shape the action potential waveform, contribute to gene expression, synaptic plasticity, neuronal differentiation, hormone secretion and pacemaker activity. In the chromaffin cells (CCs) of the adrenal medulla, Cav1.3 is highly expressed and is shown to support most of the pacemaking current that sustains action potential (AP) firings and part of the catecholamine secretion. Cav1.3 forms Ca2+-nanodomains with the fast inactivating BK channels and drives the resting SK currents. These latter set the inter-spike interval duration between consecutive spikes during spontaneous firing and the rate of spike adaptation during sustained depolarizations. Cav1.3 plays also a primary role in the switch from “tonic” to “burst” firing that occurs in mouse CCs when either the availability of voltage-gated Na channels (Nav) is reduced or the β2 subunit featuring the fast inactivating BK channels is deleted. Here, we discuss the functional role of these “neuronlike” firing modes in CCs and how Cav1.3 contributes to them. The open issue is to understand how these novel firing patterns are adapted to regulate the quantity of circulating catecholamines during resting condition or in response to acute and chronic stress.
AU - Vandael, David H
AU - Marcantoni, Andrea
AU - Carbone, Emilio
ID - 1535
IS - 2
JF - Current Molecular Pharmacology
TI - Cav1.3 channels as key regulators of neuron-like firings and catecholamine release in chromaffin cells
VL - 8
ER -
TY - JOUR
AB - Strigolactones, first discovered as germination stimulants for parasitic weeds [1], are carotenoid-derived phytohormones that play major roles in inhibiting lateral bud outgrowth and promoting plant-mycorrhizal symbiosis [2-4]. Furthermore, strigolactones are involved in the regulation of lateral and adventitious root development, root cell division [5, 6], secondary growth [7], and leaf senescence [8]. Recently, we discovered the strigolactone transporter Petunia axillaris PLEIOTROPIC DRUG RESISTANCE 1 (PaPDR1), which is required for efficient mycorrhizal colonization and inhibition of lateral bud outgrowth [9]. However, how strigolactones are transported through the plant remained unknown. Here we show that PaPDR1 exhibits a cell-type-specific asymmetric localization in different root tissues. In root tips, PaPDR1 is co-expressed with the strigolactone biosynthetic gene DAD1 (CCD8), and it is localized at the apical membrane of root hypodermal cells, presumably mediating the shootward transport of strigolactone. Above the root tip, in the hypodermal passage cells that form gates for the entry of mycorrhizal fungi, PaPDR1 is present in the outer-lateral membrane, compatible with its postulated function as strigolactone exporter from root to soil. Transport studies are in line with our localization studies since (1) a papdr1 mutant displays impaired transport of strigolactones out of the root tip to the shoot as well as into the rhizosphere and (2) DAD1 expression and PIN1/PIN2 levels change in plants deregulated for PDR1 expression, suggestive of variations in endogenous strigolactone contents. In conclusion, our results indicate that the polar localizations of PaPDR1 mediate directional shootward strigolactone transport as well as localized exudation into the soil.
AU - Sasse, Joëlle
AU - Simon, Sibu
AU - Gübeli, Christian
AU - Liu, Guowei
AU - Cheng, Xi
AU - Friml, Jirí
AU - Bouwmeester, Harro
AU - Martinoia, Enrico
AU - Borghi, Lorenzo
ID - 1536
IS - 5
JF - Current Biology
TI - Asymmetric localizations of the ABC transporter PaPDR1 trace paths of directional strigolactone transport
VL - 25
ER -
TY - JOUR
AB - 3D amoeboid cell migration is central to many developmental and disease-related processes such as cancer metastasis. Here, we identify a unique prototypic amoeboid cell migration mode in early zebrafish embryos, termed stable-bleb migration. Stable-bleb cells display an invariant polarized balloon-like shape with exceptional migration speed and persistence. Progenitor cells can be reversibly transformed into stable-bleb cells irrespective of their primary fate and motile characteristics by increasing myosin II activity through biochemical or mechanical stimuli. Using a combination of theory and experiments, we show that, in stable-bleb cells, cortical contractility fluctuations trigger a stochastic switch into amoeboid motility, and a positive feedback between cortical flows and gradients in contractility maintains stable-bleb cell polarization. We further show that rearward cortical flows drive stable-bleb cell migration in various adhesive and non-adhesive environments, unraveling a highly versatile amoeboid migration phenotype.
AU - Ruprecht, Verena
AU - Wieser, Stefan
AU - Callan Jones, Andrew
AU - Smutny, Michael
AU - Morita, Hitoshi
AU - Sako, Keisuke
AU - Barone, Vanessa
AU - Ritsch Marte, Monika
AU - Sixt, Michael K
AU - Voituriez, Raphaël
AU - Heisenberg, Carl-Philipp J
ID - 1537
IS - 4
JF - Cell
TI - Cortical contractility triggers a stochastic switch to fast amoeboid cell motility
VL - 160
ER -
TY - JOUR
AB - Systems biology rests on the idea that biological complexity can be better unraveled through the interplay of modeling and experimentation. However, the success of this approach depends critically on the informativeness of the chosen experiments, which is usually unknown a priori. Here, we propose a systematic scheme based on iterations of optimal experiment design, flow cytometry experiments, and Bayesian parameter inference to guide the discovery process in the case of stochastic biochemical reaction networks. To illustrate the benefit of our methodology, we apply it to the characterization of an engineered light-inducible gene expression circuit in yeast and compare the performance of the resulting model with models identified from nonoptimal experiments. In particular, we compare the parameter posterior distributions and the precision to which the outcome of future experiments can be predicted. Moreover, we illustrate how the identified stochastic model can be used to determine light induction patterns that make either the average amount of protein or the variability in a population of cells follow a desired profile. Our results show that optimal experiment design allows one to derive models that are accurate enough to precisely predict and regulate the protein expression in heterogeneous cell populations over extended periods of time.
AU - Ruess, Jakob
AU - Parise, Francesca
AU - Milias Argeitis, Andreas
AU - Khammash, Mustafa
AU - Lygeros, John
ID - 1538
IS - 26
JF - PNAS
TI - Iterative experiment design guides the characterization of a light-inducible gene expression circuit
VL - 112
ER -
TY - JOUR
AB - Many stochastic models of biochemical reaction networks contain some chemical species for which the number of molecules that are present in the system can only be finite (for instance due to conservation laws), but also other species that can be present in arbitrarily large amounts. The prime example of such networks are models of gene expression, which typically contain a small and finite number of possible states for the promoter but an infinite number of possible states for the amount of mRNA and protein. One of the main approaches to analyze such models is through the use of equations for the time evolution of moments of the chemical species. Recently, a new approach based on conditional moments of the species with infinite state space given all the different possible states of the finite species has been proposed. It was argued that this approach allows one to capture more details about the full underlying probability distribution with a smaller number of equations. Here, I show that the result that less moments provide more information can only stem from an unnecessarily complicated description of the system in the classical formulation. The foundation of this argument will be the derivation of moment equations that describe the complete probability distribution over the finite state space but only low-order moments over the infinite state space. I will show that the number of equations that is needed is always less than what was previously claimed and always less than the number of conditional moment equations up to the same order. To support these arguments, a symbolic algorithm is provided that can be used to derive minimal systems of unconditional moment equations for models with partially finite state space.
AU - Ruess, Jakob
ID - 1539
IS - 24
JF - Journal of Chemical Physics
TI - Minimal moment equations for stochastic models of biochemical reaction networks with partially finite state space
VL - 143
ER -
TY - JOUR
AB - Plant sexual reproduction involves highly structured and specialized organs: stamens (male) and gynoecia (female, containing ovules). These organs synchronously develop within protective flower buds, until anthesis, via tightly coordinated mechanisms that are essential for effective fertilization and production of viable seeds. The phytohormone auxin is one of the key endogenous signalling molecules controlling initiation and development of these, and other, plant organs. In particular, its uneven distribution, resulting from tightly controlled production, metabolism and directional transport, is an important morphogenic factor. In this review we discuss how developmentally controlled and localized auxin biosynthesis and transport contribute to the coordinated development of plants' reproductive organs, and their fertilized derivatives (embryos) via the regulation of auxin levels and distribution within and around them. Current understanding of the links between de novo local auxin biosynthesis, auxin transport and/or signalling is presented to highlight the importance of the non-cell autonomous action of auxin production on development and morphogenesis of reproductive organs and embryos. An overview of transcription factor families, which spatiotemporally define local auxin production by controlling key auxin biosynthetic enzymes, is also presented.
AU - Robert, Hélène
AU - Crhák Khaitová, Lucie
AU - Mroue, Souad
AU - Benková, Eva
ID - 1540
IS - 16
JF - Journal of Experimental Botany
TI - The importance of localized auxin production for morphogenesis of reproductive organs and embryos in Arabidopsis
VL - 66
ER -
TY - CONF
AB - We present XSpeed a parallel state-space exploration algorithm for continuous systems with linear dynamics and nondeterministic inputs. The motivation of having parallel algorithms is to exploit the computational power of multi-core processors to speed-up performance. The parallelization is achieved on two fronts. First, we propose a parallel implementation of the support function algorithm by sampling functions in parallel. Second, we propose a parallel state-space exploration by slicing the time horizon and computing the reachable states in the time slices in parallel. The second method can be however applied only to a class of linear systems with invertible dynamics and fixed input. A GP-GPU implementation is also presented following a lazy evaluation strategy on support functions. The parallel algorithms are implemented in the tool XSpeed. We evaluated the performance on two benchmarks including an 28 dimension Helicopter model. Comparison with the sequential counterpart shows a maximum speed-up of almost 7× on a 6 core, 12 thread Intel Xeon CPU E5-2420 processor. Our GP-GPU implementation shows a maximum speed-up of 12× over the sequential implementation and 53× over SpaceEx (LGG scenario), the state of the art tool for reachability analysis of linear hybrid systems. Experiments illustrate that our parallel algorithm with time slicing not only speeds-up performance but also improves precision.
AU - Ray, Rajarshi
AU - Gurung, Amit
AU - Das, Binayak
AU - Bartocci, Ezio
AU - Bogomolov, Sergiy
AU - Grosu, Radu
ID - 1541
TI - XSpeed: Accelerating reachability analysis on multi-core processors
VL - 9434
ER -
TY - JOUR
AB - The theory of population genetics and evolutionary computation have been evolving separately for nearly 30 years. Many results have been independently obtained in both fields and many others are unique to its respective field. We aim to bridge this gap by developing a unifying framework for evolutionary processes that allows both evolutionary algorithms and population genetics models to be cast in the same formal framework. The framework we present here decomposes the evolutionary process into its several components in order to facilitate the identification of similarities between different models. In particular, we propose a classification of evolutionary operators based on the defining properties of the different components. We cast several commonly used operators from both fields into this common framework. Using this, we map different evolutionary and genetic algorithms to different evolutionary regimes and identify candidates with the most potential for the translation of results between the fields. This provides a unified description of evolutionary processes and represents a stepping stone towards new tools and results to both fields.
AU - Paixao, Tiago
AU - Badkobeh, Golnaz
AU - Barton, Nicholas H
AU - Çörüş, Doğan
AU - Dang, Duccuong
AU - Friedrich, Tobias
AU - Lehre, Per
AU - Sudholt, Dirk
AU - Sutton, Andrew
AU - Trubenova, Barbora
ID - 1542
JF - Journal of Theoretical Biology
TI - Toward a unifying framework for evolutionary processes
VL - 383
ER -
TY - JOUR
AB - A plethora of diverse programmed cell death (PCD) processes has been described in living organisms. In animals and plants, different forms of PCD play crucial roles in development, immunity, and responses to the environment. While the molecular control of some animal PCD forms such as apoptosis is known in great detail, we still know comparatively little about the regulation of the diverse types of plant PCD. In part, this deficiency in molecular understanding is caused by the lack of reliable reporters to detect PCD processes. Here, we addressed this issue by using a combination of bioinformatics approaches to identify commonly regulated genes during diverse plant PCD processes in Arabidopsis (Arabidopsis thaliana). Our results indicate that the transcriptional signatures of developmentally controlled cell death are largely distinct from the ones associated with environmentally induced cell death. Moreover, different cases of developmental PCD share a set of cell death-associated genes. Most of these genes are evolutionary conserved within the green plant lineage, arguing for an evolutionary conserved core machinery of developmental PCD. Based on this information, we established an array of specific promoter-reporter lines for developmental PCD in Arabidopsis. These PCD indicators represent a powerful resource that can be used in addition to established morphological and biochemical methods to detect and analyze PCD processes in vivo and in planta.
AU - Olvera Carrillo, Yadira
AU - Van Bel, Michiel
AU - Van Hautegem, Tom
AU - Fendrych, Matyas
AU - Huysmans, Marlies
AU - Šimášková, Mária
AU - Van Durme, Matthias
AU - Buscaill, Pierre
AU - Rivas, Susana
AU - Coll, Núria
AU - Coppens, Frederik
AU - Maere, Steven
AU - Nowack, Moritz
ID - 1543
IS - 4
JF - Plant Physiology
TI - A conserved core of programmed cell death indicator genes discriminates developmentally and environmentally induced programmed cell death in plants
VL - 169
ER -
TY - CHAP
AB - Cell division in prokaryotes and eukaryotes is commonly initiated by the well-controlled binding of proteins to the cytoplasmic side of the cell membrane. However, a precise characterization of the spatiotemporal dynamics of membrane-bound proteins is often difficult to achieve in vivo. Here, we present protocols for the use of supported lipid bilayers to rebuild the cytokinetic machineries of cells with greatly different dimensions: the bacterium Escherichia coli and eggs of the vertebrate Xenopus laevis. Combined with total internal reflection fluorescence microscopy, these experimental setups allow for precise quantitative analyses of membrane-bound proteins. The protocols described to obtain glass-supported membranes from bacterial and vertebrate lipids can be used as starting points for other reconstitution experiments. We believe that similar biochemical assays will be instrumental to study the biochemistry and biophysics underlying a variety of complex cellular tasks, such as signaling, vesicle trafficking, and cell motility.
AU - Nguyen, Phuong
AU - Field, Christine
AU - Groen, Aaron
AU - Mitchison, Timothy
AU - Loose, Martin
ID - 1544
T2 - Building a Cell from its Components Parts
TI - Using supported bilayers to study the spatiotemporal organization of membrane-bound proteins
VL - 128
ER -
TY - JOUR
AB - Synaptic efficacy and precision are influenced by the coupling of voltage-gated Ca2+ channels (VGCCs) to vesicles. But because the topography of VGCCs and their proximity to vesicles is unknown, a quantitative understanding of the determinants of vesicular release at nanometer scale is lacking. To investigate this, we combined freeze-fracture replica immunogold labeling of Cav2.1 channels, local [Ca2+] imaging, and patch pipette perfusion of EGTA at the calyx of Held. Between postnatal day 7 and 21, VGCCs formed variable sized clusters and vesicular release became less sensitive to EGTA, whereas fixed Ca2+ buffer properties remained constant. Experimentally constrained reaction-diffusion simulations suggest that Ca2+ sensors for vesicular release are located at the perimeter of VGCC clusters (<30nm) and predict that VGCC number per cluster determines vesicular release probability without altering release time course. This "perimeter release model" provides a unifying framework accounting for developmental changes in both synaptic efficacy and time course.
AU - Nakamura, Yukihiro
AU - Harada, Harumi
AU - Kamasawa, Naomi
AU - Matsui, Ko
AU - Rothman, Jason
AU - Shigemoto, Ryuichi
AU - Silver, R Angus
AU - Digregorio, David
AU - Takahashi, Tomoyuki
ID - 1546
IS - 1
JF - Neuron
TI - Nanoscale distribution of presynaptic Ca2+ channels and its impact on vesicular release during development
VL - 85
ER -