TY - JOUR
AB - We study the problem of object recognition for categories for which we have no training examples, a task also called zero-data or zero-shot learning. This situation has hardly been studied in computer vision research, even though it occurs frequently: the world contains tens of thousands of different object classes and for only few of them image collections have been formed and suitably annotated. To tackle the problem we introduce attribute-based classification: objects are identified based on a high-level description that is phrased in terms of semantic attributes, such as the object's color or shape. Because the identification of each such property transcends the specific learning task at hand, the attribute classifiers can be pre-learned independently, e.g. from existing image datasets unrelated to the current task. Afterwards, new classes can be detected based on their attribute representation, without the need for a new training phase. In this paper we also introduce a new dataset, Animals with Attributes, of over 30,000 images of 50 animal classes, annotated with 85 semantic attributes. Extensive experiments on this and two more datasets show that attribute-based classification indeed is able to categorize images without access to any training images of the target classes.
AU - Lampert, Christoph
AU - Nickisch, Hannes
AU - Harmeling, Stefan
ID - 2516
IS - 3
JF - IEEE Transactions on Pattern Analysis and Machine Intelligence
TI - Attribute-based classification for zero-shot learning of object categories
VL - 36
ER -
TY - CONF
AB - Traditional formal methods are based on a Boolean satisfaction notion: a reactive system satisfies, or not, a given specification. We generalize formal methods to also address the quality of systems. As an adequate specification formalism we introduce the linear temporal logic LTL[F]. The satisfaction value of an LTL[F] formula is a number between 0 and 1, describing the quality of the satisfaction. The logic generalizes traditional LTL by augmenting it with a (parameterized) set F of arbitrary functions over the interval [0,1]. For example, F may contain the maximum or minimum between the satisfaction values of subformulas, their product, and their average. The classical decision problems in formal methods, such as satisfiability, model checking, and synthesis, are generalized to search and optimization problems in the quantitative setting. For example, model checking asks for the quality in which a specification is satisfied, and synthesis returns a system satisfying the specification with the highest quality. Reasoning about quality gives rise to other natural questions, like the distance between specifications. We formalize these basic questions and study them for LTL[F]. By extending the automata-theoretic approach for LTL to a setting that takes quality into an account, we are able to solve the above problems and show that reasoning about LTL[F] has roughly the same complexity as reasoning about traditional LTL.
AU - Almagor, Shaull
AU - Boker, Udi
AU - Kupferman, Orna
ID - 2517
IS - Part 2
TI - Formalizing and reasoning about quality
VL - 7966
ER -
TY - CONF
AB - A class of valued constraint satisfaction problems (VCSPs) is characterised by a valued constraint language, a fixed set of cost functions on a finite domain. An instance of the problem is specified by a sum of cost functions from the language with the goal to minimise the sum. We study which classes of finite-valued languages can be solved exactly by the basic linear programming relaxation (BLP). Thapper and Živný showed [20] that if BLP solves the language then the language admits a binary commutative fractional polymorphism. We prove that the converse is also true. This leads to a necessary and a sufficient condition which can be checked in polynomial time for a given language. In contrast, the previous necessary and sufficient condition due to [20] involved infinitely many inequalities. More recently, Thapper and Živný [21] showed (using, in particular, a technique introduced in this paper) that core languages that do not satisfy our condition are NP-hard. Taken together, these results imply that a finite-valued language can either be solved using Linear Programming or is NP-hard.
AU - Kolmogorov, Vladimir
ID - 2518
IS - 1
TI - The power of linear programming for finite-valued CSPs: A constructive characterization
VL - 7965
ER -
TY - CONF
AB - We propose a probabilistic model to infer supervised latent variables in
the Hamming space from observed data. Our model allows simultaneous
inference of the number of binary latent variables, and their values. The
latent variables preserve neighbourhood structure of the data in a sense
that objects in the same semantic concept have similar latent values, and
objects in different concepts have dissimilar latent values. We formulate
the supervised infinite latent variable problem based on an intuitive
principle of pulling objects together if they are of the same type, and
pushing them apart if they are not. We then combine this principle with a
flexible Indian Buffet Process prior on the latent variables. We show that
the inferred supervised latent variables can be directly used to perform a
nearest neighbour search for the purpose of retrieval. We introduce a new
application of dynamically extending hash codes, and show how to
effectively couple the structure of the hash codes with continuously
growing structure of the neighbourhood preserving infinite latent feature
space.
AU - Quadrianto, Novi
AU - Sharmanska, Viktoriia
AU - Knowles, David
AU - Ghahramani, Zoubin
ID - 2520
SN - 9780974903996
T2 - Proceedings of the 29th conference uncertainty in Artificial Intelligence
TI - The supervised IBP: Neighbourhood preserving infinite latent feature models
ER -
TY - JOUR
AB - Understanding the relative importance of heterosis and outbreeding depression over multiple generations is a key question in evolutionary biology and is essential for identifying appropriate genetic sources for population and ecosystem restoration. Here we use 2455 experimental crosses between 12 population pairs of the rare perennial plant Rutidosis leptorrhynchoides (Asteraceae) to investigate the multi-generational (F1, F2, F3) fitness outcomes of inter-population hybridization. We detected no evidence of outbreeding depression, with inter-population hybrids and backcrosses showing either similar fitness or significant heterosis for fitness components across the three generations. Variation in heterosis among population pairs was best explained by characteristics of the foreign source or home population, and was greatest when the source population was large, with high genetic diversity and low inbreeding, and the home population was small and inbred. Our results indicate that the primary consideration for maximizing progeny fitness following population augmentation or restoration is the use of seed from large, genetically diverse populations.
AU - Pickup, Melinda
AU - Field, David
AU - Rowell, David
AU - Young, Andrew
ID - 450
IS - 1750
JF - Proceedings of the Royal Society of London Series B Biological Sciences
TI - Source population characteristics affect heterosis following genetic rescue of fragmented plant populations
VL - 280
ER -
TY - JOUR
AB - Maternal exposure to infection occurring mid-gestation produces a three-fold increase in the risk of schizophrenia in the offspring. The critical initiating factor appears to be the maternal immune activation (MIA) that follows infection. This process can be induced in rodents by exposure of pregnant dams to the viral mimic Poly I:C, which triggers an immune response that results in structural, functional, behavioral, and electrophysiological phenotypes in the adult offspring that model those seen in schizophrenia. We used this model to explore the role of synchronization in brain neural networks, a process thought to be dysfunctional in schizophrenia and previously associated with positive, negative, and cognitive symptoms of schizophrenia. Exposure of pregnant dams to Poly I:C on GD15 produced an impairment in long-range neural synchrony in adult offspring between two regions implicated in schizophrenia pathology; the hippocampus and the medial prefrontal cortex (mPFC). This reduction in synchrony was ameliorated by acute doses of the antipsychotic clozapine. MIA animals have previously been shown to have impaired pre-pulse inhibition (PPI), a gold-standard measure of schizophrenia-like deficits in animal models. Our data showed that deficits in synchrony were positively correlated with the impairments in PPI. Subsequent analysis of LFP activity during the PPI response also showed that reduced coupling between the mPFC and the hippocampus following processing of the pre-pulse was associated with reduced PPI. The ability of the MIA intervention to model neurodevelopmental aspects of schizophrenia pathology provides a useful platform from which to investigate the ontogeny of aberrant synchronous processes. Further, the way in which the model expresses translatable deficits such as aberrant synchrony and reduced PPI will allow researchers to explore novel intervention strategies targeted to these changes.
AU - Dickerson, Desiree
AU - Bilkey, David
ID - 476
IS - DEC
JF - Frontiers in Behavioral Neuroscience
TI - Aberrant neural synchrony in the maternal immune activation model: Using translatable measures to explore targeted interventions
VL - 7
ER -
TY - JOUR
AB - Exposure of an isogenic bacterial population to a cidal antibiotic typically fails to eliminate a small fraction of refractory cells. Historically, fractional killing has been attributed to infrequently dividing or nondividing "persisters." Using microfluidic cultures and time-lapse microscopy, we found that Mycobacterium smegmatis persists by dividing in the presence of the drug isoniazid (INH). Although persistence in these studies was characterized by stable numbers of cells, this apparent stability was actually a dynamic state of balanced division and death. Single cells expressed catalase-peroxidase (KatG), which activates INH, in stochastic pulses that were negatively correlated with cell survival. These behaviors may reflect epigenetic effects, because KatG pulsing and death were correlated between sibling cells. Selection of lineages characterized by infrequent KatG pulsing could allow nonresponsive adaptation during prolonged drug exposure.
AU - Wakamoto, Yurichi
AU - Dhar, Neraaj
AU - Chait, Remy P
AU - Schneider, Katrin
AU - Signorino Gelo, François
AU - Leibler, Stanislas
AU - Mckinney, John
ID - 499
IS - 6115
JF - Science
TI - Dynamic persistence of antibiotic-stressed mycobacteria
VL - 339
ER -
TY - JOUR
AB - Background: Reassortment between the RNA segments encoding haemagglutinin (HA) and neuraminidase (NA), the major antigenic influenza proteins, produces viruses with novel HA and NA subtype combinations and has preceded the emergence of pandemic strains. It has been suggested that productive viral infection requires a balance in the level of functional activity of HA and NA, arising from their closely interacting roles in the viral life cycle, and that this functional balance could be mediated by genetic changes in the HA and NA. Here, we investigate how the selective pressure varies for H7 avian influenza HA on different NA subtype backgrounds. Results: By extending Bayesian stochastic mutational mapping methods to calculate the ratio of the rate of non-synonymous change to the rate of synonymous change (d N/d S), we found the average d N/d S across the avian influenza H7 HA1 region to be significantly greater on an N2 NA subtype background than on an N1, N3 or N7 background. Observed differences in evolutionary rates of H7 HA on different NA subtype backgrounds could not be attributed to underlying differences between avian host species or virus pathogenicity. Examination of d N/d S values for each subtype on a site-by-site basis indicated that the elevated d N/d S on the N2 NA background was a result of increased selection, rather than a relaxation of selective constraint. Conclusions: Our results are consistent with the hypothesis that reassortment exposes influenza HA to significant changes in selective pressure through genetic interactions with NA. Such epistatic effects might be explicitly accounted for in future models of influenza evolution.
AU - Ward, Melissa
AU - Lycett, Samantha
AU - Avila, Dorita
AU - Bollback, Jonathan P
AU - Leigh Brown, Andrew
ID - 500
IS - 1
JF - BMC Evolutionary Biology
TI - Evolutionary interactions between haemagglutinin and neuraminidase in avian influenza
VL - 13
ER -
TY - JOUR
AB - All known species of extant tapirs are allopatric: 1 in southeastern Asia and 3 in Central and South America. The fossil record for tapirs, however, is much wider in geographical range, including Europe, Asia, and North and South America, going back to the late Oligocene, making the present distribution a relict of the original one. We here describe a new species of living Tapirus from the Amazon rain forest, the 1st since T. bairdii Gill, 1865, and the 1st new Perissodactyla in more than 100 years, from both morphological and molecular characters. It is shorter in stature than T. terrestris (Linnaeus, 1758) and has distinctive skull morphology, and it is basal to the clade formed by T. terrestris and T. pinchaque (Roulin, 1829). This highlights the unrecognized biodiversity in western Amazonia, where the biota faces increasing threats. Local peoples have long recognized our new species, suggesting a key role for traditional knowledge in understanding the biodiversity of the region.
AU - Cozzuol, Mario
AU - Clozato, Camila
AU - Holanda, Elizete
AU - Rodrigues, Flávio
AU - Nienow, Samuel
AU - De Thoisy, Benoit
AU - Fernandes Redondo, Rodrigo A
AU - Santos, Fabrício
ID - 501
IS - 6
JF - Journal of Mammalogy
TI - A new species of tapir from the Amazon
VL - 94
ER -
TY - JOUR
AB - Blind signatures allow users to obtain signatures on messages hidden from the signer; moreover, the signer cannot link the resulting message/signature pair to the signing session. This paper presents blind signature schemes, in which the number of interactions between the user and the signer is minimal and whose blind signatures are short. Our schemes are defined over bilinear groups and are proved secure in the common-reference-string model without random oracles and under standard assumptions: CDH and the decision-linear assumption. (We also give variants over asymmetric groups based on similar assumptions.) The blind signatures are Waters signatures, which consist of 2 group elements. Moreover, we instantiate partially blind signatures, where the message consists of a part hidden from the signer and a commonly known public part, and schemes achieving perfect blindness. We propose new variants of blind signatures, such as signer-friendly partially blind signatures, where the public part can be chosen by the signer without prior agreement, 3-party blind signatures, as well as blind signatures on multiple aggregated messages provided by independent sources. We also extend Waters signatures to non-binary alphabets by proving a new result on the underlying hash function.
AU - Blazy, Olivier
AU - Fuchsbauer, Georg
AU - Pointcheval, David
AU - Vergnaud, Damien
ID - 502
IS - 5
JF - Journal of Computer Security
TI - Short blind signatures
VL - 21
ER -
TY - JOUR
AB - Alkyd resins are polyesters containing unsaturated fatty acids that are used as binding agents in paints and coatings. Chemical drying of these polyesters is based on heavy metal catalyzed cross-linking of the unsaturated fatty acid moieties. Among the heavy-metal catalysts, cobalt complexes are the most effective, yet they have been proven to be carcinogenic. Therefore, strategies to replace the cobalt-based catalyst by environmentally friendlier and less toxic alternatives are under development. Here, we demonstrate for the first time that a laccase-mediator system can effectively replace the heavy-metal catalyst and cross-link alkyd resins. Interestingly, the biocatalytic reaction does not only work in aqueous media, but also in a solid film, where enzyme diffusion is limited. Within the catalytic cycle, the mediator oxidizes the alkyd resin and is regenerated by the laccase, which is uniformly distributed within the drying film as evidenced by confocal laser scanning microscopy. During gradual build-up of molecular weight, there is a concomitant decrease of the oxygen content in the film. A new optical sensor to follow oxygen consumption during the cross-linking reaction was developed and validated with state of the art techniques. A remarkable feature is the low sample amount required, which allows faster screening of new catalysts.
AU - Greimel, Katrin
AU - Perz, Veronika
AU - Koren, Klaus
AU - Feola, Roland
AU - Temel, Armin
AU - Sohar, Christian
AU - Herrero Acero, Enrique
AU - Klimant, Ingo
AU - Guebitz, Georg
ID - 505
IS - 2
JF - Green Chemistry
TI - Banning toxic heavy-metal catalysts from paints: Enzymatic cross-linking of alkyd resins
VL - 15
ER -
TY - JOUR
AB - Fertilization in flowering plants requires the temporal and spatial coordination of many developmental processes, including pollen production, anther dehiscence, ovule production, and pollen tube elongation. However, it remains elusive as to how this coordination occurs during reproduction. Here, we present evidence that endocytosis, involving heterotetrameric adaptor protein complex 2 (AP-2), plays a crucial role in fertilization. An Arabidopsis thaliana mutant ap2m displays multiple defects in pollen production and viability, as well as elongation of staminal filaments and pollen tubes, all of which are pivotal processes needed for fertilization. Of these abnormalities, the defects in elongation of staminal filaments and pollen tubes were partially rescued by exogenous auxin. Moreover, DR5rev:GFP (for green fluorescent protein) expression was greatly reduced in filaments and anthers in ap2m mutant plants. At the cellular level, ap2m mutants displayed defects in both endocytosis of N-(3-triethylammonium-propyl)-4- (4-diethylaminophenylhexatrienyl) pyridinium dibromide, a lypophilic dye used as an endocytosis marker, and polar localization of auxin-efflux carrier PIN FORMED2 (PIN2) in the stamen filaments. Moreover, these defects were phenocopied by treatment with Tyrphostin A23, an inhibitor of endocytosis. Based on these results, we propose that AP-2-dependent endocytosis plays a crucial role in coordinating the multiple developmental aspects of male reproductive organs by modulating cellular auxin level through the regulation of the amount and polarity of PINs.
AU - Kim, Soo
AU - Xu, Zheng
AU - Song, Kyungyoung
AU - Kim, Dae
AU - Kang, Hyangju
AU - Reichardt, Ilka
AU - Sohn, Eun
AU - Friml, Jirí
AU - Juergens, Gerd
AU - Hwang, Inhwan
ID - 507
IS - 8
JF - Plant Cell
TI - Adaptor protein complex 2-mediated endocytosis is crucial for male reproductive organ development in arabidopsis
VL - 25
ER -
TY - JOUR
AB - The phagocyte NADPH oxidase catalyzes the reduction of O2 to reactive oxygen species with microbicidal activity. It is composed of two membrane-spanning subunits, gp91-phox and p22-phox (encoded by CYBB and CYBA, respectively), and three cytoplasmic subunits, p40-phox, p47-phox, and p67-phox (encoded by NCF4, NCF1, and NCF2, respectively). Mutations in any of these genes can result in chronic granulomatous disease, a primary immunodeficiency characterized by recurrent infections. Using evolutionary mapping, we determined that episodes of adaptive natural selection have shaped the extracellular portion of gp91-phox during the evolution of mammals, which suggests that this region may have a function in host-pathogen interactions. On the basis of a resequencing analysis of approximately 35 kb of CYBB, CYBA, NCF2, and NCF4 in 102 ethnically diverse individuals (24 of African ancestry, 31 of European ancestry, 24 of Asian/Oceanians, and 23 US Hispanics), we show that the pattern of CYBA diversity is compatible with balancing natural selection, perhaps mediated by catalase-positive pathogens. NCF2 in Asian populations shows a pattern of diversity characterized by a differentiated haplotype structure. Our study provides insight into the role of pathogen-driven natural selection in an innate immune pathway and sheds light on the role of CYBA in endothelial, nonphagocytic NADPH oxidases, which are relevant in the pathogenesis of cardiovascular and other complex diseases.
AU - Tarazona Santos, Eduardo
AU - Machado, Moara
AU - Magalhães, Wagner
AU - Chen, Renee
AU - Lyon, Fernanda
AU - Burdett, Laurie
AU - Crenshaw, Andrew
AU - Fabbri, Cristina
AU - Pereira, Latife
AU - Pinto, Laelia
AU - Fernandes Redondo, Rodrigo A
AU - Sestanovich, Ben
AU - Yeager, Meredith
AU - Chanock, Stephen
ID - 508
IS - 9
JF - Molecular Biology and Evolution
TI - Evolutionary dynamics of the human NADPH oxidase genes CYBB, CYBA, NCF2, and NCF4: Functional implications
VL - 30
ER -
TY - JOUR
AB - Clathrin-mediated endocytosis (CME) regulates many aspects of plant development, including hormone signaling and responses to environmental stresses. Despite the importance of this process, the machinery that regulates CME in plants is largely unknown. In mammals, the heterotetrameric ADAPTOR PROTEIN COMPLEX-2 (AP-2) is required for the formation of clathrin-coated vesicles at the plasma membrane (PM). Although the existence of AP-2 has been predicted in Arabidopsis thaliana, the biochemistry and functionality of the complex is still uncharacterized. Here, we identified all the subunits of the Arabidopsis AP-2 by tandem affinity purification and found that one of the large AP-2 subunits, AP2A1, localized at the PM and interacted with clathrin. Furthermore, endocytosis of the leucine-rich repeat receptor kinase, BRASSINOSTEROID INSENSITIVE1 (BRI1), was shown to depend on AP-2. Knockdown of the two Arabidopsis AP2A genes or overexpression of a dominant-negative version of the medium AP-2 subunit, AP2M, impaired BRI1 endocytosis and enhanced the brassinosteroid signaling. Our data reveal that the CME machinery in Arabidopsis is evolutionarily conserved and that AP-2 functions in receptormediated endocytosis.
AU - Di Rubbo, Simone
AU - Irani, Niloufer
AU - Kim, Soo
AU - Xu, Zheng
AU - Gadeyne, Astrid
AU - Dejonghe, Wim
AU - Vanhoutte, Isabelle
AU - Persiau, Geert
AU - Eeckhout, Dominique
AU - Simon, Sibu
AU - Song, Kyungyoung
AU - Kleine Vehn, Jürgen
AU - Friml, Jirí
AU - De Jaeger, Geert
AU - Van Damme, Daniël
AU - Hwang, Inhwan
AU - Russinova, Eugenia
ID - 509
IS - 8
JF - Plant Cell
TI - The clathrin adaptor complex AP-2 mediates endocytosis of brassinosteroid INSENSITIVE1 in arabidopsis
VL - 25
ER -
TY - JOUR
AB - The native auxin, indole-3-acetic acid (IAA), is a major regulator of plant growth and development. Its nonuniform distribution between cells and tissues underlies the spatiotemporal coordination of many developmental events and responses to environmental stimuli. The regulation of auxin gradients and the formation of auxin maxima/minima most likely involve the regulation of both metabolic and transport processes. In this article, we have demonstrated that 2-oxindole-3-acetic acid (oxIAA) is a major primary IAA catabolite formed in Arabidopsis thaliana root tissues. OxIAA had little biological activity and was formed rapidly and irreversibly in response to increases in auxin levels. We further showed that there is cell type-specific regulation of oxIAA levels in the Arabidopsis root apex. We propose that oxIAA is an important element in the regulation of output from auxin gradients and, therefore, in the regulation of auxin homeostasis and response mechanisms.
AU - Pěnčík, Aleš
AU - Simonovik, Biljana
AU - Petersson, Sara
AU - Henyková, Eva
AU - Simon, Sibu
AU - Greenham, Kathleen
AU - Zhang, Yi
AU - Kowalczyk, Mariusz
AU - Estelle, Mark
AU - Zažímalová, Eva
AU - Novák, Ondřej
AU - Sandberg, Göran
AU - Ljung, Karin
ID - 511
IS - 10
JF - Plant Cell
TI - Regulation of auxin homeostasis and gradients in Arabidopsis roots through the formation of the indole-3-acetic acid catabolite 2-oxindole-3-acetic acid
VL - 25
ER -
TY - JOUR
AB - In plants, changes in local auxin concentrations can trigger a range of developmental processes as distinct tissues respond differently to the same auxin stimulus. However, little is known about how auxin is interpreted by individual cell types. We performed a transcriptomic analysis of responses to auxin within four distinct tissues of the Arabidopsis thaliana root and demonstrate that different cell types show competence for discrete responses. The majority of auxin‐responsive genes displayed a spatial bias in their induction or repression. The novel data set was used to examine how auxin influences tissue‐specific transcriptional regulation of cell‐identity markers. Additionally, the data were used in combination with spatial expression maps of the root to plot a transcriptomic auxin‐response gradient across the apical and basal meristem. The readout revealed a strong correlation for thousands of genes between the relative response to auxin and expression along the longitudinal axis of the root. This data set and comparative analysis provide a transcriptome‐level spatial breakdown of the response to auxin within an organ where this hormone mediates many aspects of development.
AU - Bargmann, Bastiaan
AU - Vanneste, Steffen
AU - Krouk, Gabriel
AU - Nawy, Tal
AU - Efroni, Idan
AU - Shani, Eilon
AU - Choe, Goh
AU - Friml, Jirí
AU - Bergmann, Dominique
AU - Estelle, Mark
AU - Birnbaum, Kenneth
ID - 516
IS - 1
JF - Molecular Systems Biology
TI - A map of cell type‐specific auxin responses
VL - 9
ER -
TY - JOUR
AB - Podoplanin, a mucin-like plasma membrane protein, is expressed by lymphatic endothelial cells and responsible for separation of blood and lymphatic circulation through activation of platelets. Here we show that podoplanin is also expressed by thymic fibroblastic reticular cells (tFRC), a novel thymic medulla stroma cell type associated with thymic conduits, and involved in development of natural regulatory T cells (nTreg). Young mice deficient in podoplanin lack nTreg owing to retardation of CD4+CD25+ thymocytes in the cortex and missing differentiation of Foxp3+ thymocytes in the medulla. This might be due to CCL21 that delocalizes upon deletion of the CCL21-binding podoplanin from medullar tFRC to cortex areas. The animals do not remain devoid of nTreg but generate them delayed within the first month resulting in Th2-biased hypergammaglobulinemia but not in the death-causing autoimmune phenotype of Foxp3-deficient Scurfy mice.
AU - Fuertbauer, Elke
AU - Zaujec, Jan
AU - Uhrin, Pavel
AU - Raab, Ingrid
AU - Weber, Michele
AU - Schachner, Helga
AU - Bauer, Miroslav
AU - Schütz, Gerhard
AU - Binder, Bernd
AU - Sixt, Michael K
AU - Kerjaschki, Dontscho
AU - Stockinger, Hannes
ID - 522
IS - 1-2
JF - Immunology Letters
TI - Thymic medullar conduits-associated podoplanin promotes natural regulatory T cells
VL - 154
ER -
TY - JOUR
AB - The apical-basal axis of the early plant embryo determines the body plan of the adult organism. To establish a polarized embryonic axis, plants evolved a unique mechanism that involves directional, cell-to-cell transport of the growth regulator auxin. Auxin transport relies on PIN auxin transporters [1], whose polar subcellular localization determines the flow directionality. PIN-mediated auxin transport mediates the spatial and temporal activity of the auxin response machinery [2-7] that contributes to embryo patterning processes, including establishment of the apical (shoot) and basal (root) embryo poles [8]. However, little is known of upstream mechanisms guiding the (re)polarization of auxin fluxes during embryogenesis [9]. Here, we developed a model of plant embryogenesis that correctly generates emergent cell polarities and auxin-mediated sequential initiation of apical-basal axis of plant embryo. The model relies on two precisely localized auxin sources and a feedback between auxin and the polar, subcellular PIN transporter localization. Simulations reproduced PIN polarity and auxin distribution, as well as previously unknown polarization events during early embryogenesis. The spectrum of validated model predictions suggests that our model corresponds to a minimal mechanistic framework for initiation and orientation of the apical-basal axis to guide both embryonic and postembryonic plant development.
AU - Wabnik, Krzysztof T
AU - Robert, Hélène
AU - Smith, Richard
AU - Friml, Jirí
ID - 527
IS - 24
JF - Current Biology
TI - Modeling framework for the establishment of the apical-basal embryonic axis in plants
VL - 23
ER -
TY - JOUR
AB - Establishment of the embryonic axis foreshadows the main body axis of adults both in plants and in animals, but underlying mechanisms are considered distinct. Plants utilize directional, cell-to-cell transport of the growth hormone auxin [1, 2] to generate an asymmetric auxin response that specifies the embryonic apical-basal axis [3-6]. The auxin flow directionality depends on the polarized subcellular localization of PIN-FORMED (PIN) auxin transporters [7, 8]. It remains unknown which mechanisms and spatial cues guide cell polarization and axis orientation in early embryos. Herein, we provide conceptually novel insights into the formation of embryonic axis in Arabidopsis by identifying a crucial role of localized tryptophan-dependent auxin biosynthesis [9-12]. Local auxin production at the base of young embryos and the accompanying PIN7-mediated auxin flow toward the proembryo are required for the apical auxin response maximum and the specification of apical embryonic structures. Later in embryogenesis, the precisely timed onset of localized apical auxin biosynthesis mediates PIN1 polarization, basal auxin response maximum, and specification of the root pole. Thus, the tight spatiotemporal control of distinct local auxin sources provides a necessary, non-cell-autonomous trigger for the coordinated cell polarization and subsequent apical-basal axis orientation during embryogenesis and, presumably, also for other polarization events during postembryonic plant life [13, 14].
AU - Robert, Hélène
AU - Grones, Peter
AU - Stepanova, Anna
AU - Robles, Linda
AU - Lokerse, Annemarie
AU - Alonso, Jose
AU - Weijers, Dolf
AU - Friml, Jirí
ID - 528
IS - 24
JF - Current Biology
TI - Local auxin sources orient the apical basal axis in arabidopsis embryos
VL - 23
ER -
TY - GEN
AB - In this work we present a flexible tool for tumor progression, which simulates the evolutionary dynamics of cancer. Tumor progression implements a multi-type branching process where the key parameters are the fitness landscape, the mutation rate, and the average time of cell division. The fitness of a cancer cell depends on the mutations it has accumulated. The input to our tool could be any fitness landscape, mutation rate, and cell division time, and the tool produces the growth dynamics and all relevant statistics.
AU - Reiter, Johannes
AU - Bozic, Ivana
AU - Chatterjee, Krishnendu
AU - Nowak, Martin
ID - 5399
SN - 2664-1690
TI - TTP: Tool for Tumor Progression
ER -
TY - GEN
AB - We consider partially observable Markov decision processes (POMDPs) with ω-regular conditions specified as parity objectives. The class of ω-regular languages extends regular languages to infinite strings and provides a robust specification language to express all properties used in verification, and parity objectives are canonical forms to express ω-regular conditions. The qualitative analysis problem given a POMDP and a parity objective asks whether there is a strategy to ensure that the objective is satis- fied with probability 1 (resp. positive probability). While the qualitative analysis problems are known to be undecidable even for very special cases of parity objectives, we establish decidability (with optimal complexity) of the qualitative analysis problems for POMDPs with all parity objectives under finite- memory strategies. We establish asymptotically optimal (exponential) memory bounds and EXPTIME- completeness of the qualitative analysis problems under finite-memory strategies for POMDPs with parity objectives.
AU - Chatterjee, Krishnendu
AU - Chmelik, Martin
AU - Tracol, Mathieu
ID - 5400
SN - 2664-1690
TI - What is decidable about partially observable Markov decision processes with ω-regular objectives
ER -
TY - GEN
AB - This document is created as a part of the project “Repository for Research Data at IST Austria”. It summarises the actual initiatives, projects and standards related to the project. It supports the preparation of standards and specifications for the project, which should be considered and followed to ensure interoperability and visibility of the uploaded data.
AU - Porsche, Jana
ID - 5401
TI - Initiatives and projects related to RD
ER -
TY - GEN
AB - Linearizability requires that the outcome of calls by competing threads to a concurrent data structure is the same as some sequential execution where each thread has exclusive access to the data structure. In an ordered data structure, such as a queue or a stack, linearizability is ensured by requiring threads commit in the order dictated by the sequential semantics of the data structure; e.g., in a concurrent queue implementation a dequeue can only remove the oldest element.
In this paper, we investigate the impact of this strict ordering, by comparing what linearizability allows to what existing implementations do. We first give an operational definition for linearizability which allows us to build the most general linearizable implementation as a transition system for any given sequential specification. We then use this operational definition to categorize linearizable implementations based on whether they are bound or free. In a bound implementation, whenever all threads observe the same logical state, the updates to the logical state and the temporal order of commits coincide. All existing queue implementations we know of are bound. We then proceed to present, to the best of our knowledge, the first ever free queue implementation. Our experiments show that free implementations have the potential for better performance by suffering less from contention.
AU - Henzinger, Thomas A
AU - Sezgin, Ali
ID - 5402
SN - 2664-1690
TI - How free is your linearizable concurrent data structure?
ER -
TY - GEN
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 every 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 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 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 mean-payoff games) that is not known to be in polynomial time.
AU - Chatterjee, Krishnendu
AU - Ibsen-Jensen, Rasmus
ID - 5403
SN - 2664-1690
TI - Qualitative analysis of concurrent mean-payoff games
ER -
TY - GEN
AB - We study finite-state two-player (zero-sum) concurrent mean-payoff games played on a graph. We focus on the important sub-class of ergodic games where all states are visited infinitely often with probability 1. The algorithmic study of ergodic games was initiated in a seminal work of Hoffman and Karp in 1966, but all basic complexity questions have remained unresolved. Our main results for ergodic games are as follows: We establish (1) an optimal exponential bound on the patience of stationary strategies (where patience of a distribution is the inverse of the smallest positive probability and represents a complexity measure of a stationary strategy); (2) the approximation problem lie in FNP; (3) the approximation problem is at least as hard as the decision problem for simple stochastic games (for which NP and coNP is the long-standing best known bound). We show that the exact value can be expressed in the existential theory of the reals, and also establish square-root sum hardness for a related class of games.
AU - Chatterjee, Krishnendu
AU - Ibsen-Jensen, Rasmus
ID - 5404
SN - 2664-1690
TI - The complexity of ergodic games
ER -
TY - GEN
AB - The theory of graph games is the foundation for modeling and synthesizing reactive processes. In the synthesis of stochastic processes, we use 2-1/2-player games where some transitions of the game graph are controlled by two adversarial players, the System and the Environment, and the other transitions are determined probabilistically. We consider 2-1/2-player games where the objective of the System is the conjunction of a qualitative objective (specified as a parity condition) and a quantitative objective (specified as a mean-payoff condition). We establish that the problem of deciding whether the System can ensure that the probability to satisfy the mean-payoff parity objective is at least a given threshold is in NP ∩ coNP, matching the best known bound in the special case of 2-player games (where all transitions are deterministic) with only parity objectives, or with only mean-payoff objectives. We present an algorithm running
in time O(d · n^{2d}·MeanGame) to compute the set of almost-sure winning states from which the objective
can be ensured with probability 1, where n is the number of states of the game, d the number of priorities
of the parity objective, and MeanGame is the complexity to compute the set of almost-sure winning states
in 2-1/2-player mean-payoff games. Our results are useful in the synthesis of stochastic reactive systems
with both functional requirement (given as a qualitative objective) and performance requirement (given
as a quantitative objective).
AU - Chatterjee, Krishnendu
AU - Doyen, Laurent
AU - Gimbert, Hugo
AU - Oualhadj, Youssouf
ID - 5405
SN - 2664-1690
TI - Perfect-information stochastic mean-payoff parity games
ER -
TY - GEN
AB - We consider the distributed synthesis problem fortemporal logic specifications. Traditionally, the problem has been studied for LTL, and the previous results show that the problem is decidable iff there is no information fork in the architecture. We consider the problem for fragments of LTLand our main results are as follows: (1) We show that the problem is undecidable for architectures with information forks even for the fragment of LTL with temporal operators restricted to next and eventually. (2) For specifications restricted to globally along with non-nested next operators, we establish decidability (in EXPSPACE) for star architectures where the processes receive disjoint inputs, whereas we establish undecidability for architectures containing an information fork-meet structure. (3)Finally, we consider LTL without the next operator, and establish decidability (NEXPTIME-complete) for all architectures for a fragment that consists of a set of safety assumptions, and a set of guarantees where each guarantee is a safety, reachability, or liveness condition.
AU - Chatterjee, Krishnendu
AU - Henzinger, Thomas A
AU - Otop, Jan
AU - Pavlogiannis, Andreas
ID - 5406
SN - 2664-1690
TI - Distributed synthesis for LTL Fragments
ER -
TY - GEN
AB - This document is created as a part of the project “Repository for Research Data at IST Austria”. It summarises the mandatory features, which need to be fulfilled to provide an institutional repository as a platform and also a service to the scientists at the institute. It also includes optional features, which would be of strong benefit for the scientists and would increase the usage of the repository, and hence the visibility of research at IST Austria.
AU - Porsche, Jana
ID - 5407
TI - Technical requirements and features
ER -
TY - GEN
AB - We consider two-player partial-observation stochastic games where player 1 has partial observation and player 2 has perfect observation. The winning condition we study are omega-regular conditions specified as parity objectives. The qualitative analysis problem given a partial-observation stochastic game and a parity objective asks whether there is a strategy to ensure that the objective is satisfied with probability 1 (resp. positive probability). While the qualitative analysis problems are known to be undecidable even for very special cases of parity objectives, they were shown to be decidable in 2EXPTIME under finite-memory strategies. We improve the complexity and show that the qualitative analysis problems for partial-observation stochastic parity games under finite-memory strategies are
EXPTIME-complete; and also establish optimal (exponential) memory bounds for finite-memory strategies required for qualitative analysis.
AU - Chatterjee, Krishnendu
AU - Doyen, Laurent
AU - Nain, Sumit
AU - Vardi, Moshe
ID - 5408
SN - 2664-1690
TI - The complexity of partial-observation stochastic parity games with finite-memory strategies
ER -
TY - GEN
AB - The edit distance between two (untimed) traces is the minimum cost of a sequence of edit operations (insertion, deletion, or substitution) needed to transform one trace to the other. Edit distances have been extensively studied in the untimed setting, and form the basis for approximate matching of sequences in different domains such as coding theory, parsing, and speech recognition.
In this paper, we lift the study of edit distances from untimed languages to the timed setting. We define an edit distance between timed words which incorporates both the edit distance between the untimed words and the absolute difference in timestamps. Our edit distance between two timed words is computable in polynomial time. Further, we show that the edit distance between a timed word and a timed language generated by a timed automaton, defined as the edit distance between the word and the closest word in the language, is PSPACE-complete. While computing the edit distance between two timed automata is undecidable, we show that the approximate version, where we decide if the edit distance between two timed automata is either less than a given parameter or more than delta away from the parameter, for delta>0, can be solved in exponential space and is EXPSPACE-hard. Our definitions and techniques can be generalized to the setting of hybrid systems, and we show analogous decidability results for rectangular automata.
AU - Chatterjee, Krishnendu
AU - Ibsen-Jensen, Rasmus
AU - Majumdar, Rupak
ID - 5409
SN - 2664-1690
TI - Edit distance for timed automata
ER -
TY - GEN
AB - Board games, like Tic-Tac-Toe and CONNECT-4, play an important role not only in development of mathematical and logical skills, but also in 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.
Our approach 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. Also, the presence of such states for standard game variants like Tic-Tac-Toe on board size 4x4 opens up new games to be played that have not been played for ages since the default start state is heavily biased.
AU - Ahmed, Umair
AU - Chatterjee, Krishnendu
AU - Gulwani, Sumit
ID - 5410
SN - 2664-1690
TI - Automatic generation of alternative starting positions for traditional board games
ER -
TY - CHAP
AU - Dragoi, Cezara
AU - Gupta, Ashutosh
AU - Henzinger, Thomas A
ID - 5747
SN - 0302-9743
T2 - Computer Aided Verification
TI - Automatic Linearizability Proofs of Concurrent Objects with Cooperating Updates
VL - 8044
ER -
TY - JOUR
AB - We consider non-interacting particles subject to a fixed external potential V and a self-generated magnetic field B. The total energy includes the field energy β∫B2 and we minimize over all particle states and magnetic fields. In the case of spin-1/2 particles this minimization leads to the coupled Maxwell-Pauli system. The parameter β tunes the coupling strength between the field and the particles and it effectively determines the strength of the field. We investigate the stability and the semiclassical asymptotics, h→0, of the total ground state energy E(β,h,V). The relevant parameter measuring the field strength in the semiclassical limit is κ=βh. We are not able to give the exact leading order semiclassical asymptotics uniformly in κ or even for fixed κ. We do however give upper and lower bounds on E with almost matching dependence on κ. In the simultaneous limit h→0 and κ→∞ we show that the standard non-magnetic Weyl asymptotics holds. The same result also holds for the spinless case, i.e. where the Pauli operator is replaced by the Schrödinger operator.
AU - Erdös, László
AU - Fournais, Søren
AU - Solovej, Jan
ID - 2698
IS - 6
JF - Journal of the European Mathematical Society
TI - Stability and semiclassics in self-generated fields
VL - 15
ER -
TY - CONF
AB - Even though both population and quantitative genetics, and evolutionary computation, deal with the same questions, they have developed largely independently of each other. I review key results from each field, emphasising those that apply independently of the (usually unknown) relation between genotype and phenotype. The infinitesimal model provides a simple framework for predicting the response of complex traits to selection, which in biology has proved remarkably successful. This allows one to choose the schedule of population sizes and selection intensities that will maximise the response to selection, given that the total number of individuals realised, C = ∑t Nt, is constrained. This argument shows that for an additive trait (i.e., determined by the sum of effects of the genes), the optimum population size and the maximum possible response (i.e., the total change in trait mean) are both proportional to √C.
AU - Barton, Nicholas H
AU - Paixao, Tiago
ID - 2718
T2 - Proceedings of the 15th annual conference on Genetic and evolutionary computation
TI - Can quantitative and population genetics help us understand evolutionary computation?
ER -
TY - CONF
AB - Prediction of the evolutionary process is a long standing problem both in the theory of evolutionary biology and evolutionary computation (EC). It has long been realized that heritable variation is crucial to both the response to selection and the success of genetic algorithms. However, not all variation contributes in the same way to the response. Quantitative genetics has developed a large body of work trying to estimate and understand how different components of the variance in fitness in the population contribute to the response to selection. We illustrate how to apply some concepts of quantitative genetics to the analysis of genetic algorithms. In particular, we derive estimates for the short term prediction of the response to selection and we use variance decomposition to gain insight on local aspects of the landscape. Finally, we propose a new population based genetic algorithm that uses these methods to improve its operation.
AU - Paixao, Tiago
AU - Barton, Nicholas H
ID - 2719
T2 - Proceedings of the 15th annual conference on Genetic and evolutionary computation
TI - A variance decomposition approach to the analysis of genetic algorithms
ER -
TY - JOUR
AB - Knowledge of the rate and fitness effects of mutations is essential for understanding the process of evolution. Mutations are inherently difficult to study because they are rare and are frequently eliminated by natural selection. In the ciliate Tetrahymena thermophila, mutations can accumulate in the germline genome without being exposed to selection. We have conducted a mutation accumulation (MA) experiment in this species. Assuming that all mutations are deleterious and have the same effect, we estimate that the deleterious mutation rate per haploid germline genome per generation is U = 0.0047 (95% credible interval: 0.0015, 0.0125), and that germline mutations decrease fitness by s = 11% when expressed in a homozygous state (95% CI: 4.4%, 27%). We also estimate that deleterious mutations are partially recessive on average (h = 0.26; 95% CI: –0.022, 0.62) and that the rate of lethal mutations is <10% of the deleterious mutation rate. Comparisons between the observed evolutionary responses in the germline and somatic genomes and the results from individual-based simulations of MA suggest that the two genomes have similar mutational parameters. These are the first estimates of the deleterious mutation rate and fitness effects from the eukaryotic supergroup Chromalveolata and are within the range of those of other eukaryotes.
AU - Long, Hongan
AU - Paixao, Tiago
AU - Azevedo, Ricardo
AU - Zufall, Rebecca
ID - 2720
IS - 2
JF - Genetics
TI - Accumulation of spontaneous mutations in the ciliate Tetrahymena thermophila
VL - 195
ER -
TY - JOUR
AB - We consider random n×n matrices of the form (XX*+YY*)^{-1/2}YY*(XX*+YY*)^{-1/2}, where X and Y have independent entries with zero mean and variance one. These matrices are the natural generalization of the Gaussian case, which are known as MANOVA matrices and which have joint eigenvalue density given by the third classical ensemble, the Jacobi ensemble. We show that, away from the spectral edge, the eigenvalue density converges to the limiting density of the Jacobi ensemble even on the shortest possible scales of order 1/n (up to log n factors). This result is the analogue of the local Wigner semicircle law and the local Marchenko-Pastur law for general MANOVA matrices.
AU - Erdös, László
AU - Farrell, Brendan
ID - 2782
IS - 6
JF - Journal of Statistical Physics
TI - Local eigenvalue density for general MANOVA matrices
VL - 152
ER -
TY - JOUR
AB - A novel Taylor-Couette system has been constructed for investigations of transitional as well as high Reynolds number turbulent flows in very large aspect ratios. The flexibility of the setup enables studies of a variety of problems regarding hydrodynamic instabilities and turbulence in rotating flows. The inner and outer cylinders and the top and bottom endplates can be rotated independently with rotation rates of up to 30 Hz, thereby covering five orders of magnitude in Reynolds numbers (Re = 101-106). The radius ratio can be easily changed, the highest realized one is η = 0.98 corresponding to an aspect ratio of 260 gap width in the vertical and 300 in the azimuthal direction. For η < 0.98 the aspect ratio can be dynamically changed during measurements and complete transparency in the radial direction over the full length of the cylinders is provided by the usage of a precision glass inner cylinder. The temperatures of both cylinders are controlled independently. Overall this apparatus combines an unmatched variety in geometry, rotation rates, and temperatures, which is provided by a sophisticated high-precision bearing system. Possible applications are accurate studies of the onset of turbulence and spatio-temporal intermittent flow patterns in very large domains, transport processes of turbulence at high Re, the stability of Keplerian flows for different boundary conditions, and studies of baroclinic instabilities.
AU - Avila, Kerstin
AU - Hof, Björn
ID - 2806
IS - 6
JF - Review of Scientific Instruments
TI - High-precision Taylor-Couette experiment to study subcritical transitions and the role of boundary conditions and size effects
VL - 84
ER -
TY - CONF
AB - We consider several basic problems of algebraic topology, with connections to combinatorial and geometric questions, from the point of view of computational complexity. The extension problem asks, given topological spaces X; Y , a subspace A ⊆ X, and a (continuous) map f : A → Y , whether f can be extended to a map X → Y . For computational purposes, we assume that X and Y are represented as finite simplicial complexes, A is a subcomplex of X, and f is given as a simplicial map. In this generality the problem is undecidable, as follows from Novikov's result from the 1950s on uncomputability of the fundamental group π1(Y ). We thus study the problem under the assumption that, for some k ≥ 2, Y is (k - 1)-connected; informally, this means that Y has \no holes up to dimension k-1" (a basic example of such a Y is the sphere Sk). We prove that, on the one hand, this problem is still undecidable for dimX = 2k. On the other hand, for every fixed k ≥ 2, we obtain an algorithm that solves the extension problem in polynomial time assuming Y (k - 1)-connected and dimX ≤ 2k - 1. For dimX ≤ 2k - 2, the algorithm also provides a classification of all extensions up to homotopy (continuous deformation). This relies on results of our SODA 2012 paper, and the main new ingredient is a machinery of objects with polynomial-time homology, which is a polynomial-time analog of objects with effective homology developed earlier by Sergeraert et al. We also consider the computation of the higher homotopy groups πk(Y ), k ≥ 2, for a 1-connected Y . Their computability was established by Brown in 1957; we show that πk(Y ) can be computed in polynomial time for every fixed k ≥ 2. On the other hand, Anick proved in 1989 that computing πk(Y ) is #P-hard if k is a part of input, where Y is a cell complex with certain rather compact encoding. We strengthen his result to #P-hardness for Y given as a simplicial complex.
AU - Čadek, Martin
AU - Krcál, Marek
AU - Matoušek, Jiří
AU - Vokřínek, Lukáš
AU - Wagner, Uli
ID - 2807
T2 - 45th Annual ACM Symposium on theory of computing
TI - Extending continuous maps: Polynomiality and undecidability
ER -
TY - JOUR
AB - In order to establish a reference for analysis of the function of auxin and the auxin biosynthesis regulators SHORT INTERNODE/ STYLISH (SHI/STY) during Physcomitrella patens reproductive development, we have described male (antheridial) and female (archegonial) development in detail, including temporal and positional information of organ initiation. This has allowed us to define discrete stages of organ morphogenesis and to show that reproductive organ development in P. patens is highly organized and that organ phyllotaxis differs between vegetative and reproductive development. Using the PpSHI1 and PpSHI2 reporter and knockout lines, the auxin reporters GmGH3pro:GUS and PpPINApro:GFP-GUS, and the auxin-conjugating transgene PpSHI2pro:IAAL, we could show that the PpSHI genes, and by inference also auxin, play important roles for reproductive organ development in moss. The PpSHI genes are required for the apical opening of the reproductive organs, the final differentiation of the egg cell, and the progression of canal cells into a cell death program. The apical cells of the archegonium, the canal cells, and the egg cell are also sites of auxin responsiveness and are affected by reduced levels of active auxin, suggesting that auxin mediates PpSHI function in the reproductive organs.
AU - Landberg, Katarina
AU - Pederson, Eric
AU - Viaene, Tom
AU - Bozorg, Behruz
AU - Friml, Jirí
AU - Jönsson, Henrik
AU - Thelander, Mattias
AU - Sundberg, Eva
ID - 2808
IS - 3
JF - Plant Physiology
TI - The moss physcomitrella patens reproductive organ development is highly organized, affected by the two SHI/STY genes and by the level of active auxin in the SHI/STY expression domain
VL - 162
ER -
TY - JOUR
AB - The epistatic interactions that underlie evolutionary constraint have mainly been studied for constant external conditions. However, environmental changes may modulate epistasis and hence affect genetic constraints. Here we investigate genetic constraints in the adaptive evolution of a novel regulatory function in variable environments, using the lac repressor, LacI, as a model system. We have systematically reconstructed mutational trajectories from wild type LacI to three different variants that each exhibit an inverse response to the inducing ligand IPTG, and analyzed the higher-order interactions between genetic and environmental changes. We find epistasis to depend strongly on the environment. As a result, mutational steps essential to inversion but inaccessible by positive selection in one environment, become accessible in another. We present a graphical method to analyze the observed complex higher-order interactions between multiple mutations and environmental change, and show how the interactions can be explained by a combination of mutational effects on allostery and thermodynamic stability. This dependency of genetic constraint on the environment should fundamentally affect evolutionary dynamics and affects the interpretation of phylogenetic data.
AU - De Vos, Marjon
AU - Poelwijk, Frank
AU - Battich, Nico
AU - Ndika, Joseph
AU - Tans, Sander
ID - 2810
IS - 6
JF - PLoS Genetics
TI - Environmental dependence of genetic constraint
VL - 9
ER -
TY - JOUR
AB - In pipe, channel, and boundary layer flows turbulence first occurs intermittently in space and time: at moderate Reynolds numbers domains of disordered turbulent motion are separated by quiescent laminar regions. Based on direct numerical simulations of pipe flow we argue here that the spatial intermittency has its origin in a nearest neighbor interaction between turbulent regions. We further show that in this regime turbulent flows are intrinsically intermittent with a well-defined equilibrium turbulent fraction but without ever assuming a steady pattern. This transition scenario is analogous to that found in simple models such as coupled map lattices. The scaling observed implies that laminar intermissions of the turbulent flow will persist to arbitrarily large Reynolds numbers.
AU - Avila, Marc
AU - Hof, Björn
ID - 2811
IS - 6
JF - Physical Review E
TI - Nature of laminar-turbulence intermittency in shear flows
VL - 87
ER -
TY - CONF
AB - We consider the problem of deciding whether the persistent homology group of a simplicial pair (K, L) can be realized as the homology H* (X) of some complex X with L ⊂ X ⊂ K. We show that this problem is NP-complete even if K is embedded in ℝ3. As a consequence, we show that it is NP-hard to simplify level and sublevel sets of scalar functions on S3 within a given tolerance constraint. This problem has relevance to the visualization of medical images by isosurfaces. We also show an implication to the theory of well groups of scalar functions: not every well group can be realized by some level set, and deciding whether a well group can be realized is NP-hard.
AU - Attali, Dominique
AU - Bauer, Ulrich
AU - Devillers, Olivier
AU - Glisse, Marc
AU - Lieutier, André
ID - 2812
T2 - Proceedings of the 29th annual symposium on Computational Geometry
TI - Homological reconstruction and simplification in R3
ER -
TY - JOUR
AB - Turbulence is ubiquitous in nature, yet even for the case of ordinary Newtonian fluids like water, our understanding of this phenomenon is limited. Many liquids of practical importance are more complicated (e.g., blood, polymer melts, paints), however; they exhibit elastic as well as viscous characteristics, and the relation between stress and strain is nonlinear. We demonstrate here for a model system of such complex fluids that at high shear rates, turbulence is not simply modified as previously believed but is suppressed and replaced by a different type of disordered motion, elasto-inertial turbulence. Elasto-inertial turbulence is found to occur at much lower Reynolds numbers than Newtonian turbulence, and the dynamical properties differ significantly. The friction scaling observed coincides with the so-called "maximum drag reduction" asymptote, which is exhibited by a wide range of viscoelastic fluids.
AU - Samanta, Devranjan
AU - Dubief, Yves
AU - Holzner, Markus
AU - Schäfer, Christof
AU - Morozov, Alexander
AU - Wagner, Christian
AU - Hof, Björn
ID - 2813
IS - 26
JF - PNAS
TI - Elasto-inertial turbulence
VL - 110
ER -
TY - JOUR
AB - We study the problem of generating a test sequence that achieves maximal coverage for a reactive system under test. We formulate the problem as a repeated game between the tester and the system, where the system state space is partitioned according to some coverage criterion and the objective of the tester is to maximize the set of partitions (or coverage goals) visited during the game. We show the complexity of the maximal coverage problem for non-deterministic systems is PSPACE-complete, but is NP-complete for deterministic systems. For the special case of non-deterministic systems with a re-initializing "reset" action, which represent running a new test input on a re-initialized system, we show that the complexity is coNP-complete. Our proof technique for reset games uses randomized testing strategies that circumvent the exponentially large memory requirement of deterministic testing strategies. We also discuss the memory requirement for deterministic strategies and extensions of our results to other models, such as pushdown systems and timed systems.
AU - Chatterjee, Krishnendu
AU - Alfaro, Luca
AU - Majumdar, Ritankar
ID - 2814
IS - 2
JF - International Journal of Foundations of Computer Science
TI - The complexity of coverage
VL - 24
ER -
TY - JOUR
AB - The fact that a sum of isotropic Gaussian kernels can have more modes than kernels is surprising. Extra (ghost) modes do not exist in ℝ1 and are generally not well studied in higher dimensions. We study a configuration of n+1 Gaussian kernels for which there are exactly n+2 modes. We show that all modes lie on a finite set of lines, which we call axes, and study the restriction of the Gaussian mixture to these axes in order to discover that there are an exponential number of critical points in this configuration. Although the existence of ghost modes remained unknown due to the difficulty of finding examples in ℝ2, we show that the resilience of ghost modes grows like the square root of the dimension. In addition, we exhibit finite configurations of isotropic Gaussian kernels with superlinearly many modes.
AU - Edelsbrunner, Herbert
AU - Fasy, Brittany Terese
AU - Rote, Günter
ID - 2815
IS - 4
JF - Discrete & Computational Geometry
TI - Add isotropic Gaussian kernels at own risk: More and more resilient modes in higher dimensions
VL - 49
ER -
TY - JOUR
AB - In solid tumors, targeted treatments can lead to dramatic regressions, but responses are often short-lived because resistant cancer cells arise. The major strategy proposed for overcoming resistance is combination therapy. We present a mathematical model describing the evolutionary dynamics of lesions in response to treatment. We first studied 20 melanoma patients receiving vemurafenib. We then applied our model to an independent set of pancreatic, colorectal, and melanoma cancer patients with metastatic disease. We find that dual therapy results in long-term disease control for most patients, if there are no single mutations that cause cross-resistance to both drugs; in patients with large disease burden, triple therapy is needed. We also find that simultaneous therapy with two drugs is much more effective than sequential therapy. Our results provide realistic expectations for the efficacy of new drug combinations and inform the design of trials for new cancer therapeutics.
AU - Božić, Ivana
AU - Reiter, Johannes
AU - Allen, Benjamin
AU - Antal, Tibor
AU - Chatterjee, Krishnendu
AU - Shah, Preya
AU - Moon, Yo
AU - Yaqubie, Amin
AU - Kelly, Nicole
AU - Le, Dung
AU - Lipson, Evan
AU - Chapman, Paul
AU - Diaz, Luis
AU - Vogelstein, Bert
AU - Nowak, Martin
ID - 2816
JF - eLife
TI - Evolutionary dynamics of cancer in response to targeted combination therapy
VL - 2
ER -
TY - JOUR
AB - The basic idea of evolutionary game theory is that payoff determines reproductive rate. Successful individuals have a higher payoff and produce more offspring. But in evolutionary and ecological situations there is not only reproductive rate but also carrying capacity. Individuals may differ in their exposure to density limiting effects. Here we explore an alternative approach to evolutionary game theory by assuming that the payoff from the game determines the carrying capacity of individual phenotypes. Successful strategies are less affected by density limitation (crowding) and reach higher equilibrium abundance. We demonstrate similarities and differences between our framework and the standard replicator equation. Our equation is defined on the positive orthant, instead of the simplex, but has the same equilibrium points as the replicator equation. Linear stability analysis produces the classical conditions for asymptotic stability of pure strategies, but the stability properties of internal equilibria can differ in the two frameworks. For example, in a two-strategy game with an internal equilibrium that is always stable under the replicator equation, the corresponding equilibrium can be unstable in the new framework resulting in a limit cycle.
AU - Novak, Sebastian
AU - Chatterjee, Krishnendu
AU - Nowak, Martin
ID - 2817
JF - Journal of Theoretical Biology
TI - Density games
VL - 334
ER -
TY - JOUR
AB - Models of neural responses to stimuli with complex spatiotemporal correlation structure often assume that neurons are selective for only a small number of linear projections of a potentially high-dimensional input. In this review, we explore recent modeling approaches where the neural response depends on the quadratic form of the input rather than on its linear projection, that is, the neuron is sensitive to the local covariance structure of the signal preceding the spike. To infer this quadratic dependence in the presence of arbitrary (e.g., naturalistic) stimulus distribution, we review several inference methods, focusing in particular on two information theory–based approaches (maximization of stimulus energy and of noise entropy) and two likelihood-based approaches (Bayesian spike-triggered covariance and extensions of generalized linear models). We analyze the formal relationship between the likelihood-based and information-based approaches to demonstrate how they lead to consistent inference. We demonstrate the practical feasibility of these procedures by using model neurons responding to a flickering variance stimulus.
AU - Rajan, Kanaka
AU - Marre, Olivier
AU - Tkacik, Gasper
ID - 2818
IS - 7
JF - Neural Computation
TI - Learning quadratic receptive fields from neural responses to natural stimuli
VL - 25
ER -
TY - CONF
AB - We introduce quantatitive timed refinement metrics and quantitative timed simulation functions, incorporating zenoness checks, for timed systems. These functions assign positive real numbers between zero and infinity which quantify the timing mismatches between two timed systems, amongst non-zeno runs. We quantify timing mismatches in three ways: (1) the maximum timing mismatch that can arise, (2) the "steady-state" maximum timing mismatches, where initial transient timing mismatches are ignored; and (3) the (long-run) average timing mismatches amongst two systems. These three kinds of mismatches constitute three important types of timing differences. Our event times are the global times, measured from the start of the system execution, not just the time durations of individual steps. We present algorithms over timed automata for computing the three quantitative simulation functions to within any desired degree of accuracy. In order to compute the values of the quantitative simulation functions, we use a game theoretic formulation. We introduce two new kinds of objectives for two player games on finite state game graphs: (1) eventual debit-sum level objectives, and (2) average debit-sum level objectives. We present algorithms for computing the optimal values for these objectives for player 1, and then use these algorithms to compute the values of the quantitative timed simulation functions.
AU - Chatterjee, Krishnendu
AU - Prabhu, Vinayak
ID - 2819
T2 - Proceedings of the 16th International Conference on Hybrid Systems: Computation and Control
TI - Quantitative timed simulation functions and refinement metrics for real-time systems
VL - 1
ER -