TY - GEN
AU - Quadrianto, Novi
AU - Lampert, Christoph
ED - Dubitzky, Werner
ED - Wolkenhauer, Olaf
ED - Cho, Kwang
ED - Yokota, Hiroki
ID - 3321
T2 - Encyclopedia of Systems Biology
TI - Kernel based learning
VL - 3
ER -
TY - JOUR
AB - We consider Markov decision processes (MDPs) with Büchi (liveness) objectives. We consider the problem of computing the set of almost-sure winning states from where the objective can be ensured with probability 1. Our contributions are as follows: First, we present the first subquadratic symbolic algorithm to compute the almost-sure winning set for MDPs with Büchi objectives; our algorithm takes O(n · √ m) symbolic steps as compared to the previous known algorithm that takes O(n 2) symbolic steps, where n is the number of states and m is the number of edges of the MDP. In practice MDPs have constant out-degree, and then our symbolic algorithm takes O(n · √ n) symbolic steps, as compared to the previous known O(n 2) symbolic steps algorithm. Second, we present a new algorithm, namely win-lose algorithm, with the following two properties: (a) the algorithm iteratively computes subsets of the almost-sure winning set and its complement, as compared to all previous algorithms that discover the almost-sure winning set upon termination; and (b) requires O(n · √ K) symbolic steps, where K is the maximal number of edges of strongly connected components (scc's) of the MDP. The win-lose algorithm requires symbolic computation of scc's. Third, we improve the algorithm for symbolic scc computation; the previous known algorithm takes linear symbolic steps, and our new algorithm improves the constants associated with the linear number of steps. In the worst case the previous known algorithm takes 5×n symbolic steps, whereas our new algorithm takes 4×n symbolic steps.
AU - Chatterjee, Krishnendu
AU - Henzinger, Monika
AU - Joglekar, Manas
AU - Shah, Nisarg
ID - 2831
IS - 3
JF - Formal Methods in System Design
TI - Symbolic algorithms for qualitative analysis of Markov decision processes with Büchi objectives
VL - 42
ER -
TY - JOUR
AB - In this paper, we present the first output-sensitive algorithm to compute the persistence diagram of a filtered simplicial complex. For any Γ > 0, it returns only those homology classes with persistence at least Γ. Instead of the classical reduction via column operations, our algorithm performs rank computations on submatrices of the boundary matrix. For an arbitrary constant δ ∈ (0, 1), the running time is O (C (1 - δ) Γ R d (n) log n), where C (1 - δ) Γ is the number of homology classes with persistence at least (1 - δ) Γ, n is the total number of simplices in the complex, d its dimension, and R d (n) is the complexity of computing the rank of an n × n matrix with O (d n) nonzero entries. Depending on the choice of the rank algorithm, this yields a deterministic O (C (1 - δ) Γ n 2.376) algorithm, an O (C (1 - δ) Γ n 2.28) Las-Vegas algorithm, or an O (C (1 - δ) Γ n 2 + ε{lunate}) Monte-Carlo algorithm for an arbitrary ε{lunate} > 0. The space complexity of the Monte-Carlo version is bounded by O (d n) = O (n log n).
AU - Chen, Chao
AU - Kerber, Michael
ID - 2939
IS - 4
JF - Computational Geometry: Theory and Applications
TI - An output sensitive algorithm for persistent homology
VL - 46
ER -
TY - THES
AB - Motivated by the analysis of highly dynamic message-passing systems, i.e. unbounded thread creation, mobility, etc. we present a framework for the analysis of depth-bounded systems. Depth-bounded systems are one of the most expressive known fragment of the π-calculus for which interesting verification problems are still decidable. Even though they are infinite state systems depth-bounded systems are well-structured, thus can be analyzed algorithmically. We give an interpretation of depth-bounded systems as graph-rewriting systems. This gives more flexibility and ease of use to apply depth-bounded systems to other type of systems like shared memory concurrency.
First, we develop an adequate domain of limits for depth-bounded systems, a prerequisite for the effective representation of downward-closed sets. Downward-closed sets are needed by forward saturation-based algorithms to represent potentially infinite sets of states. Then, we present an abstract interpretation framework to compute the covering set of well-structured transition systems. Because, in general, the covering set is not computable, our abstraction over-approximates the actual covering set. Our abstraction captures the essence of acceleration based-algorithms while giving up enough precision to ensure convergence. We have implemented the analysis in the PICASSO tool and show that it is accurate in practice. Finally, we build some further analyses like termination using the covering set as starting point.
AU - Zufferey, Damien
ID - 1405
TI - Analysis of dynamic message passing programs
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 - 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 - 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 - 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 - 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 - 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 - 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 - CONF
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 - 2279
TI - Looking at mean-payoff and total-payoff through windows
VL - 8172
ER -
TY - CONF
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 - Božić, Ivana
AU - Chatterjee, Krishnendu
AU - Nowak, Martin
ID - 2000
T2 - Proceedings of 25th Int. Conf. on Computer Aided Verification
TI - TTP: Tool for tumor progression
VL - 8044
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 - CONF
AB - We consider partially observable Markov decision processes (POMDPs) with ω-regular conditions specified as parity objectives. The qualitative analysis problem given a POMDP 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, we establish decidability (with optimal EXPTIME-complete complexity) of the qualitative analysis problems for POMDPs with all parity objectives under finite-memory strategies. We also establish asymptotically optimal (exponential) memory bounds.
AU - Chatterjee, Krishnendu
AU - Chmelik, Martin
AU - Tracol, Mathieu
ID - 2295
TI - What is decidable about partially observable Markov decision processes with omega-regular objectives
VL - 23
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 - 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 - 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 - 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 - CONF
AB - We consider the distributed synthesis problem for temporal 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 LTL and 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 - 1376
T2 - 13th International Conference on Formal Methods in Computer-Aided Design
TI - Distributed synthesis for LTL fragments
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 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 - CONF
AB - We define the model-measuring problem: given a model M and specification φ, what is the maximal distance ρ such that all models M′ within distance ρ from M satisfy (or violate) φ. The model measuring problem presupposes a distance function on models. We concentrate on automatic distance functions, which are defined by weighted automata. The model-measuring problem subsumes several generalizations of the classical model-checking problem, in particular, quantitative model-checking problems that measure the degree of satisfaction of a specification, and robustness problems that measure how much a model can be perturbed without violating the specification. We show that for automatic distance functions, and ω-regular linear-time and branching-time specifications, the model-measuring problem can be solved. We use automata-theoretic model-checking methods for model measuring, replacing the emptiness question for standard word and tree automata by the optimal-weight question for the weighted versions of these automata. We consider weighted automata that accumulate weights by maximizing, summing, discounting, and limit averaging. We give several examples of using the model-measuring problem to compute various notions of robustness and quantitative satisfaction for temporal specifications.
AU - Henzinger, Thomas A
AU - Otop, Jan
ID - 2327
TI - From model checking to model measuring
VL - 8052
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 - GEN
AB - In order to guarantee that each method of a data structure updates the logical state exactly once, al-most all non-blocking implementations employ Compare-And-Swap (CAS) based synchronization. For FIFO queue implementations this translates into concurrent enqueue or dequeue methods competing among themselves to update the same variable, the tail or the head, respectively, leading to high contention and poor scalability. Recent non-blocking queue implementations try to alleviate high contentionby increasing the number of contention points, all the while using CAS-based synchronization. Furthermore, obtaining a wait-free implementation with competition is achieved by additional synchronization which leads to further degradation of performance.In this paper we formalize the notion of competitiveness of a synchronizing statement which can beused as a measure for the scalability of concurrent implementations. We present a new queue implementation, the Speculative Pairing (SP) queue, which, as we show, decreases competitiveness by using Fetch-And-Increment (FAI) instead of CAS. We prove that the SP queue is linearizable and lock-free.We also show that replacing CAS with FAI leads to wait-freedom for dequeue methods without an adverse effect on performance. In fact, our experiments suggest that the SP queue can perform and scale better than the state-of-the-art queue implementations.
AU - Henzinger, Thomas A
AU - Payer, Hannes
AU - Sezgin, Ali
ID - 6440
SN - 2664-1690
TI - Replacing competition with cooperation to achieve scalable lock-free FIFO queues
ER -
TY - CONF
AB - Two-player games on graphs are central in many problems in formal verification and program analysis such as synthesis and verification of open systems. In this work, we consider both finite-state game graphs, and recursive game graphs (or pushdown game graphs) that model the control flow of sequential programs with recursion. The objectives we study are multidimensional mean-payoff objectives, where the goal of player 1 is to ensure that the mean-payoff is non-negative in all dimensions. In pushdown games two types of strategies are relevant: (1) global strategies, that depend on the entire global history; and (2) modular strategies, that have only local memory and thus do not depend on the context of invocation. Our main contributions are as follows: (1) We show that finite-state multidimensional mean-payoff games can be solved in polynomial time if the number of dimensions and the maximal absolute value of the weights are fixed; whereas if the number of dimensions is arbitrary, then the problem is known to be coNP-complete. (2) We show that pushdown graphs with multidimensional mean-payoff objectives can be solved in polynomial time. For both (1) and (2) our algorithms are based on hyperplane separation technique. (3) For pushdown games under global strategies both one and multidimensional mean-payoff objectives problems are known to be undecidable, and we show that under modular strategies the multidimensional problem is also undecidable; under modular strategies the one-dimensional problem is NP-complete. We show that if the number of modules, the number of exits, and the maximal absolute value of the weights are fixed, then pushdown games under modular strategies with one-dimensional mean-payoff objectives can be solved in polynomial time, and if either the number of exits or the number of modules is unbounded, then the problem is NP-hard. (4) Finally we show that a fixed parameter tractable algorithm for finite-state multidimensional mean-payoff games or pushdown games under modular strategies with one-dimensional mean-payoff objectives would imply the fixed parameter tractability of parity games.
AU - Chatterjee, Krishnendu
AU - Velner, Yaron
ID - 2329
TI - Hyperplane separation technique for multidimensional mean-payoff games
VL - 8052
ER -
TY - JOUR
AB - Background: Monoclonal antibodies (mAb), such as trastuzumab are a valuable addition to breast cancer therapy.
Data obtained from neoadjuvant settings revealed that antibody-dependent cell-mediated cytotoxicity (ADCC) is a
major mechanism of action for the mAb trastuzumab. Conflicting results still call into question whether disease
progression, prolonged treatment or concomitant chemotherapy influences ADCC and related immunological
phenomena.
Methods: We analyzed the activity of ADCC and antibody-dependent cell-mediated phagocytosis (ADCP) of
peripheral blood mononuclear cells (PBMCs) from human epidermal growth factor receptor 2 (HER2/neu) positive
breast cancer patients receiving trastuzumab therapy either in an adjuvant (n = 13) or metastatic (n = 15) setting as
well as from trastuzumab treatment-naive (t-naive) HER2/neu negative patients (n = 15). PBMCs from healthy volunteers
(n = 24) were used as controls. ADCC and ADCP activity was correlated with the expression of antibody binding
Fc-gamma receptor (FcγR)I (CD64), FcγRII (CD32) and FcγRIII (CD16) on CD14+ (monocytes) and CD56+ (NK) cells, as well as the expression of CD107a+ (LAMP-1) on CD56+ cells and the total amount of CD4+CD25+FOXP3+ (Treg) cells. In metastatic patients, markers were correlated with progression-free survival (PFS).
Results: ADCC activity was significantly down regulated in metastatic, adjuvant and t-naive patient cohorts as compared to healthy controls. Reduced ADCC activity was inversely correlated with the expression of CD107a on CD56+
cells in adjuvant patients. ADCC and ADCP activity of the patient cohorts were similar, regardless of treatment duration
or additional chemotherapy. PFS in metastatic patients inversely correlated with the number of peripheral Treg cells.
Conclusion: The reduction of ADCC in patients as compared to healthy controls calls for adjuvant strategies, such as
immune-enhancing agents, to improve the activity of trastuzumab. However, efficacy of trastuzumab-specific ADCC
and ADCP appears not to be affected by treatment duration, disease progression or concomitant chemotherapy. This
finding supports the application of trastuzumab at any stage of the disease.
AU - Petricevic, Branka
AU - Laengle, Johannes
AU - Singer, Josef
AU - Sachet, Monika
AU - Fazekas, Judit
AU - Steger, Guenther
AU - Bartsch, Rupert
AU - Jensen-Jarolim, Erika
AU - Bergmann, Michael
ID - 8245
JF - Journal of Translational Medicine
SN - 1479-5876
TI - Trastuzumab mediates antibody-dependent cell-mediated cytotoxicity and phagocytosis to the same extent in both adjuvant and metastatic HER2/neu breast cancer patients
VL - 11
ER -
TY - JOUR
AB - The transition of proteins from their soluble functional state to amyloid fibrils and aggregates is associated with the onset of several human diseases. Protein aggregation often requires some structural reshaping and the subsequent formation of intermolecular contacts. Therefore, the study of the conformation of excited protein states and their ability to form oligomers is of primary importance for understanding the molecular basis of amyloid fibril formation. Here, we investigated the oligomerization processes that occur along the folding of the amyloidogenic human protein β2-microglobulin. The combination of real-time two-dimensional NMR data with real-time small-angle X-ray scattering measurements allowed us to derive thermodynamic and kinetic information on protein oligomerization of different conformational states populated along the folding pathways. In particular, we could demonstrate that a long-lived folding intermediate (I-state) has a higher propensity to oligomerize compared to the native state. Our data agree well with a simple five-state kinetic model that involves only monomeric and dimeric species. The dimers have an elongated shape with the dimerization interface located at the apical side of β2-microglobulin close to Pro32, the residue that has a trans conformation in the I-state and a cis conformation in the native (N) state. Our experimental data suggest that partial unfolding in the apical half of the protein close to Pro32 leads to an excited state conformation with enhanced propensity for oligomerization. This excited state becomes more populated in the transient I-state due to the destabilization of the native conformation by the trans-Pro32 configuration.
AU - Rennella, E.
AU - Cutuil, T.
AU - Schanda, Paul
AU - Ayala, I.
AU - Gabel, F.
AU - Forge, V.
AU - Corazza, A.
AU - Esposito, G.
AU - Brutscher, B.
ID - 8462
IS - 15
JF - Journal of Molecular Biology
KW - Molecular Biology
SN - 0022-2836
TI - Oligomeric states along the folding pathways of β2-microglobulin: Kinetics, thermodynamics, and structure
VL - 425
ER -
TY - JOUR
AB - To fight infectious diseases, host immune defenses are employed at multiple levels. Sanitary behavior, such as pathogen avoidance and removal, acts as a first line of defense to prevent infection [1] before activation of the physiological immune system. Insect societies have evolved a wide range of collective hygiene measures and intensive health care toward pathogen-exposed group members [2]. One of the most common behaviors is allogrooming, in which nestmates remove infectious particles from the body surfaces of exposed individuals [3]. Here we show that, in invasive garden ants, grooming of fungus-exposed brood is effective beyond the sheer mechanical removal of fungal conidiospores; it also includes chemical disinfection through the application of poison produced by the ants themselves. Formic acid is the main active component of the poison. It inhibits fungal growth of conidiospores remaining on the brood surface after grooming and also those collected in the mouth of the grooming ant. This dual function is achieved by uptake of the poison droplet into the mouth through acidopore self-grooming and subsequent application onto the infectious brood via brood grooming. This extraordinary behavior extends the current understanding of grooming and the establishment of social immunity in insect societies.
AU - Tragust, Simon
AU - Mitteregger, Barbara
AU - Barone, Vanessa
AU - Konrad, Matthias
AU - Ugelvig, Line V
AU - Cremer, Sylvia
ID - 2926
IS - 1
JF - Current Biology
TI - Ants disinfect fungus-exposed brood by oral uptake and spread of their poison
VL - 23
ER -
TY - CONF
AB - In this paper, we introduce the powerful framework of graph games for the analysis of real-time scheduling with firm deadlines. We introduce a novel instance of a partial-observation game that is suitable for this purpose, and prove decidability of all the involved decision problems. We derive a graph game that allows the automated computation of the competitive ratio (along with an optimal witness algorithm for the competitive ratio) and establish an NP-completeness proof for the graph game problem. For a given on-line algorithm, we present polynomial time solution for computing (i) the worst-case utility; (ii) the worst-case utility ratio w.r.t. a clairvoyant off-line algorithm; and (iii) the competitive ratio. A major strength of the proposed approach lies in its flexibility w.r.t. incorporating additional constraints on the adversary and/or the algorithm, including limited maximum or average load, finiteness of periods of overload, etc., which are easily added by means of additional instances of standard objective functions for graph games.
AU - Chatterjee, Krishnendu
AU - Kößler, Alexander
AU - Schmid, Ulrich
ID - 2820
SN - 978-1-4503-1567-8
T2 - Proceedings of the 16th International conference on Hybrid systems: Computation and control
TI - Automated analysis of real-time scheduling using graph games
ER -
TY - JOUR
AB - As sessile organisms, plants have to be able to adapt to a continuously changing environment. Plants that perceive some of these changes as stress signals activate signaling pathways to modulate their development and to enable them to survive. The complex responses to environmental cues are to a large extent mediated by plant hormones that together orchestrate the final plant response. The phytohormone cytokinin is involved in many plant developmental processes. Recently, it has been established that cytokinin plays an important role in stress responses, but does not act alone. Indeed, the hormonal control of plant development and stress adaptation is the outcome of a complex network of multiple synergistic and antagonistic interactions between various hormones. Here, we review the recent findings on the cytokinin function as part of this hormonal network. We focus on the importance of the crosstalk between cytokinin and other hormones, such as abscisic acid, jasmonate, salicylic acid, ethylene, and auxin in the modulation of plant development and stress adaptation. Finally, the impact of the current research in the biotechnological industry will be discussed.
AU - O'Brien, José
AU - Benková, Eva
ID - 827
JF - Frontiers in Plant Science
TI - Cytokinin cross talking during biotic and abiotic stress responses
VL - 4
ER -
TY - JOUR
AB - The plant root system is essential for providing anchorage to the soil, supplying minerals and water, and synthesizing metabolites. It is a dynamic organ modulated by external cues such as environmental signals, water and nutrients availability, salinity and others. Lateral roots (LRs) are initiated from the primary root post-embryonically, after which they progress through discrete developmental stages which can be independently controlled, providing a high level of plasticity during root system formation. Within this review, main contributions are presented, from the classical forward genetic screens to the more recent high-throughput approaches, combined with computer model predictions, dissecting how LRs and thereby root system architecture is established and developed.
AU - Cuesta, Candela
AU - Wabnik, Krzysztof T
AU - Benková, Eva
ID - 828
JF - Frontiers in Plant Science
TI - Systems approaches to study root architecture dynamics
VL - 4
ER -
TY - CONF
AB - Software model checking, as an undecidable problem, has three possible outcomes: (1) the program satisfies the specification, (2) the program does not satisfy the specification, and (3) the model checker fails. The third outcome usually manifests itself in a space-out, time-out, or one component of the verification tool giving up; in all of these failing cases, significant computation is performed by the verification tool before the failure, but no result is reported. We propose to reformulate the model-checking problem as follows, in order to have the verification tool report a summary of the performed work even in case of failure: given a program and a specification, the model checker returns a condition Ψ - usually a state predicate - such that the program satisfies the specification under the condition Ψ - that is, as long as the program does not leave the states in which Ψ is satisfied. In our experiments, we investigated as one major application of conditional model checking the sequential combination of model checkers with information passing. We give the condition that one model checker produces, as input to a second conditional model checker, such that the verification problem for the second is restricted to the part of the state space that is not covered by the condition, i.e., the second model checker works on the problems that the first model checker could not solve. Our experiments demonstrate that repeated application of conditional model checkers, passing information from one model checker to the next, can significantly improve the verification results and performance, i.e., we can now verify programs that we could not verify before.
AU - Beyer, Dirk
AU - Henzinger, Thomas A
AU - Keremoglu, Mehmet
AU - Wendler, Philipp
ID - 1384
T2 - Proceedings of the ACM SIGSOFT 20th International Symposium on the Foundations of Software Engineering
TI - Conditional model checking: A technique to pass information between verifiers
ER -
TY - CONF
AB - Leakage resilient cryptography attempts to incorporate side-channel leakage into the black-box security model and designs cryptographic schemes that are provably secure within it. Informally, a scheme is leakage-resilient if it remains secure even if an adversary learns a bounded amount of arbitrary information about the schemes internal state. Unfortunately, most leakage resilient schemes are unnecessarily complicated in order to achieve strong provable security guarantees. As advocated by Yu et al. [CCS’10], this mostly is an artefact of the security proof and in practice much simpler construction may already suffice to protect against realistic side-channel attacks. In this paper, we show that indeed for simpler constructions leakage-resilience can be obtained when we aim for relaxed security notions where the leakage-functions and/or the inputs to the primitive are chosen non-adaptively. For example, we show that a three round Feistel network instantiated with a leakage resilient PRF yields a leakage resilient PRP if the inputs are chosen non-adaptively (This complements the result of Dodis and Pietrzak [CRYPTO’10] who show that if a adaptive queries are allowed, a superlogarithmic number of rounds is necessary.) We also show that a minor variation of the classical GGM construction gives a leakage resilient PRF if both, the leakage-function and the inputs, are chosen non-adaptively.
AU - Faust, Sebastian
AU - Pietrzak, Krzysztof Z
AU - Schipper, Joachim
ID - 2048
T2 - Conference proceedings CHES 2012
TI - Practical leakage-resilient symmetric cryptography
VL - 7428
ER -
TY - CONF
AB - We propose a new authentication protocol that is provably secure based on a ring variant of the learning parity with noise (LPN) problem. The protocol follows the design principle of the LPN-based protocol from Eurocrypt’11 (Kiltz et al.), and like it, is a two round protocol secure against active attacks. Moreover, our protocol has small communication complexity and a very small footprint which makes it applicable in scenarios that involve low-cost, resource-constrained devices.
Performance-wise, our protocol is more efficient than previous LPN-based schemes, such as the many variants of the Hopper-Blum (HB) protocol and the aforementioned protocol from Eurocrypt’11. Our implementation results show that it is even comparable to the standard challenge-and-response protocols based on the AES block-cipher. Our basic protocol is roughly 20 times slower than AES, but with the advantage of having 10 times smaller code size. Furthermore, if a few hundred bytes of non-volatile memory are available to allow the storage of some off-line pre-computations, then the online phase of our protocols is only twice as slow as AES.
AU - Heyse, Stefan
AU - Kiltz, Eike
AU - Lyubashevsky, Vadim
AU - Paar, Christof
AU - Pietrzak, Krzysztof Z
ID - 2049
T2 - Conference proceedings FSE 2012
TI - Lapin: An efficient authentication protocol based on ring-LPN
VL - 7549
ER -
TY - JOUR
AB - Nestin-cre transgenic mice have been widely used to direct recombination to neural stem cells (NSCs) and intermediate neural progenitor cells (NPCs). Here we report that a readily utilized, and the only commercially available, Nestin-cre line is insufficient for directing recombination in early embryonic NSCs and NPCs. Analysis of recombination efficiency in multiple cre-dependent reporters and a genetic mosaic line revealed consistent temporal and spatial patterns of recombination in NSCs and NPCs. For comparison we utilized a knock-in Emx1cre line and found robust recombination in NSCs and NPCs in ventricular and subventricular zones of the cerebral cortices as early as embryonic day 12.5. In addition we found that the rate of Nestin-cre driven recombination only reaches sufficiently high levels in NSCs and NPCs during late embryonic and early postnatal periods. These findings are important when commercially available cre lines are considered for directing recombination to embryonic NSCs and NPCs.
AU - Liang, Huixuan
AU - Hippenmeyer, Simon
AU - Ghashghaei, H.
ID - 2263
IS - 12
JF - Biology open
TI - A Nestin-cre transgenic mouse is insufficient for recombination in early embryonic neural progenitors
VL - 1
ER -
TY - JOUR
AB - We introduce propagation models (PMs), a formalism able to express several kinds of equations that describe the behavior of biochemical reaction networks. Furthermore, we introduce the propagation abstract data type (PADT), which separates concerns regarding different numerical algorithms for the transient analysis of biochemical reaction networks from concerns regarding their implementation, thus allowing for portable and efficient solutions. The state of a propagation abstract data type is given by a vector that assigns mass values to a set of nodes, and its (next) operator propagates mass values through this set of nodes. We propose an approximate implementation of the (next) operator, based on threshold abstraction, which propagates only "significant" mass values and thus achieves a compromise between efficiency and accuracy. Finally, we give three use cases for propagation models: the chemical master equation (CME), the reaction rate equation (RRE), and a hybrid method that combines these two equations. These three applications use propagation models in order to propagate probabilities and/or expected values and variances of the model's variables.
AU - Henzinger, Thomas A
AU - Mateescu, Maria
ID - 2302
IS - 2
JF - IEEE ACM Transactions on Computational Biology and Bioinformatics
TI - The propagation approach for computing biochemical reaction networks
VL - 10
ER -
TY - JOUR
AB - The kingdom of fungi provides model organisms for biotechnology, cell biology, genetics, and life sciences in general. Only when their phylogenetic relationships are stably resolved, can individual results from fungal research be integrated into a holistic picture of biology. However, and despite recent progress, many deep relationships within the fungi remain unclear. Here, we present the first phylogenomic study of an entire eukaryotic kingdom that uses a consistency criterion to strengthen phylogenetic conclusions. We reason that branches (splits) recovered with independent data and different tree reconstruction methods are likely to reflect true evolutionary relationships. Two complementary phylogenomic data sets based on 99 fungal genomes and 109 fungal expressed sequence tag (EST) sets analyzed with four different tree reconstruction methods shed light from different angles on the fungal tree of life. Eleven additional data sets address specifically the phylogenetic position of Blastocladiomycota, Ustilaginomycotina, and Dothideomycetes, respectively. The combined evidence from the resulting trees supports the deep-level stability of the fungal groups toward a comprehensive natural system of the fungi. In addition, our analysis reveals methodologically interesting aspects. Enrichment for EST encoded data-a common practice in phylogenomic analyses-introduces a strong bias toward slowly evolving and functionally correlated genes. Consequently, the generalization of phylogenomic data sets as collections of randomly selected genes cannot be taken for granted. A thorough characterization of the data to assess possible influences on the tree reconstruction should therefore become a standard in phylogenomic analyses.
AU - Ebersberger, Ingo
AU - De Matos Simoes, Ricardo
AU - Kupczok, Anne
AU - Gube, Matthias
AU - Kothe, Erika
AU - Voigt, Kerstin
AU - Von Haeseler, Arndt
ID - 2411
IS - 5
JF - Molecular Biology and Evolution
TI - A consistent phylogenetic backbone for the fungi
VL - 29
ER -
TY - JOUR
AB - We show that bosons interacting via pair potentials with negative scattering length form bound states for a suitable number of particles. In other words, the absence of many-particle bound states of any kind implies the non-negativity of the scattering length of the interaction potential.
AU - Seiringer, Robert
ID - 2318
IS - 3
JF - Journal of Spectral Theory
TI - Absence of bound states implies non-negativity of the scattering length
VL - 2
ER -
TY - CONF
AB - We consider Markov decision processes (MDPs) with specifications given as Büchi (liveness) objectives. We consider the problem of computing the set of almost-sure winning vertices from where the objective can be ensured with probability 1. We study for the first time the average case complexity of the classical algorithm for computing the set of almost-sure winning vertices for MDPs with Büchi objectives. Our contributions are as follows: First, we show that for MDPs with constant out-degree the expected number of iterations is at most logarithmic and the average case running time is linear (as compared to the worst case linear number of iterations and quadratic time complexity). Second, for the average case analysis over all MDPs we show that the expected number of iterations is constant and the average case running time is linear (again as compared to the worst case linear number of iterations and quadratic time complexity). Finally we also show that given that all MDPs are equally likely, the probability that the classical algorithm requires more than constant number of iterations is exponentially small.
AU - Chatterjee, Krishnendu
AU - Joglekar, Manas
AU - Shah, Nisarg
ID - 2715
TI - Average case analysis of the classical algorithm for Markov decision processes with Büchi objectives
VL - 18
ER -
TY - CONF
AB - We study the problem of maximum marginal prediction (MMP) in probabilistic graphical models, a task that occurs, for example, as the Bayes optimal decision rule under a Hamming loss. MMP is typically performed as a two-stage procedure: one estimates each variable's marginal probability and then forms a prediction from the states of maximal probability. In this work we propose a simple yet effective technique for accelerating MMP when inference is sampling-based: instead of the above two-stage procedure we directly estimate the posterior probability of each decision variable. This allows us to identify the point of time when we are sufficiently certain about any individual decision. Whenever this is the case, we dynamically prune the variables we are confident about from the underlying factor graph. Consequently, at any time only samples of variables whose decision is still uncertain need to be created. Experiments in two prototypical scenarios, multi-label classification and image inpainting, show that adaptive sampling can drastically accelerate MMP without sacrificing prediction accuracy.
AU - Lampert, Christoph
ID - 2825
TI - Dynamic pruning of factor graphs for maximum marginal prediction
VL - 1
ER -
TY - JOUR
AB - We study evolutionary game theory in a setting where individuals learn from each other. We extend the traditional approach by assuming that a population contains individuals with different learning abilities. In particular, we explore the situation where individuals have different search spaces, when attempting to learn the strategies of others. The search space of an individual specifies the set of strategies learnable by that individual. The search space is genetically given and does not change under social evolutionary dynamics. We introduce a general framework and study a specific example in the context of direct reciprocity. For this example, we obtain the counter intuitive result that cooperation can only evolve for intermediate benefit-to-cost ratios, while small and large benefit-to-cost ratios favor defection. Our paper is a step toward making a connection between computational learning theory and evolutionary game dynamics.
AU - Chatterjee, Krishnendu
AU - Zufferey, Damien
AU - Nowak, Martin
ID - 2848
JF - Journal of Theoretical Biology
TI - Evolutionary game dynamics in populations with different learners
VL - 301
ER -
TY - JOUR
AU - Edelsbrunner, Herbert
AU - Strelkova, Nataliya
ID - 2849
IS - 6
JF - Russian Mathematical Surveys
TI - On the configuration space of Steiner minimal trees
VL - 67
ER -
TY - CONF
AB - Formal verification aims to improve the quality of hardware and software by detecting errors before they do harm. At the basis of formal verification lies the logical notion of correctness, which purports to capture whether or not a circuit or program behaves as desired. We suggest that the boolean partition into correct and incorrect systems falls short of the practical need to assess the behavior of hardware and software in a more nuanced fashion against multiple criteria.
AU - Henzinger, Thomas A
ID - 2888
T2 - Conference proceedings MODELS 2012
TI - Quantitative reactive models
VL - 7590
ER -
TY - CONF
AB - Systems are often specified using multiple requirements on their behavior. In practice, these requirements can be contradictory. The classical approach to specification, verification, and synthesis demands more detailed specifications that resolve any contradictions in the requirements. These detailed specifications are usually large, cumbersome, and hard to maintain or modify. In contrast, quantitative frameworks allow the formalization of the intuitive idea that what is desired is an implementation that comes "closest" to satisfying the mutually incompatible requirements, according to a measure of fit that can be defined by the requirements engineer. One flexible framework for quantifying how "well" an implementation satisfies a specification is offered by simulation distances that are parameterized by an error model. We introduce this framework, study its properties, and provide an algorithmic solution for the following quantitative synthesis question: given two (or more) behavioral requirements specified by possibly incompatible finite-state machines, and an error model, find the finite-state implementation that minimizes the maximal simulation distance to the given requirements. Furthermore, we generalize the framework to handle infinite alphabets (for example, realvalued domains). We also demonstrate how quantitative specifications based on simulation distances might lead to smaller and easier to modify specifications. Finally, we illustrate our approach using case studies on error correcting codes and scheduler synthesis.
AU - Cerny, Pavol
AU - Gopi, Sivakanth
AU - Henzinger, Thomas A
AU - Radhakrishna, Arjun
AU - Totla, Nishant
ID - 2890
T2 - Proceedings of the tenth ACM international conference on Embedded software
TI - Synthesis from incompatible specifications
ER -
TY - CONF
AB - Quantitative automata are nondeterministic finite automata with edge weights. They value a
run by some function from the sequence of visited weights to the reals, and value a word by its
minimal/maximal run. They generalize boolean automata, and have gained much attention in
recent years. Unfortunately, important automaton classes, such as sum, discounted-sum, and
limit-average automata, cannot be determinized. Yet, the quantitative setting provides the potential
of approximate determinization. We define approximate determinization with respect to
a distance function, and investigate this potential.
We show that sum automata cannot be determinized approximately with respect to any
distance function. However, restricting to nonnegative weights allows for approximate determinization
with respect to some distance functions.
Discounted-sum automata allow for approximate determinization, as the influence of a word’s
suffix is decaying. However, the naive approach, of unfolding the automaton computations up
to a sufficient level, is shown to be doubly exponential in the discount factor. We provide an
alternative construction that is singly exponential in the discount factor, in the precision, and
in the number of states. We prove matching lower bounds, showing exponential dependency on
each of these three parameters.
Average and limit-average automata are shown to prohibit approximate determinization with
respect to any distance function, and this is the case even for two weights, 0 and 1.
AU - Boker, Udi
AU - Henzinger, Thomas A
ID - 2891
T2 - Leibniz International Proceedings in Informatics
TI - Approximate determinization of quantitative automata
VL - 18
ER -
TY - JOUR
AB - We present an algorithm for simplifying linear cartographic objects and results obtained with a computer program implementing this algorithm.
AU - Edelsbrunner, Herbert
AU - Musin, Oleg
AU - Ukhalov, Alexey
AU - Yakimova, Olga
AU - Alexeev, Vladislav
AU - Bogaevskaya, Victoriya
AU - Gorohov, Andrey
AU - Preobrazhenskaya, Margarita
ID - 2902
IS - 6
JF - Modeling and Analysis of Information Systems
TI - Fractal and computational geometry for generalizing cartographic objects
VL - 19
ER -
TY - CONF
AB - In order to enjoy a digital version of the Jordan Curve Theorem, it is common to use the closed topology for the foreground and the open topology for the background of a 2-dimensional binary image. In this paper, we introduce a single topology that enjoys this theorem for all thresholds decomposing a real-valued image into foreground and background. This topology is easy to construct and it generalizes to n-dimensional images.
AU - Edelsbrunner, Herbert
AU - Symonova, Olga
ID - 2903
TI - The adaptive topology of a digital image
ER -
TY - JOUR
AB - Generalized van der Corput sequences are onedimensional, infinite sequences in the unit interval. They are generated from permutations in integer base b and are the building blocks of the multi-dimensional Halton sequences. Motivated by recent progress of Atanassov on the uniform distribution behavior of Halton sequences, we study, among others, permutations of the form P(i) = ai (mod b) for coprime integers a and b. We show that multipliers a that either divide b - 1 or b + 1 generate van der Corput sequences with weak distribution properties. We give explicit lower bounds for the asymptotic distribution behavior of these sequences and relate them to sequences generated from the identity permutation in smaller bases, which are, due to Faure, the weakest distributed generalized van der Corput sequences.
AU - Pausinger, Florian
ID - 2904
IS - 3
JF - Journal de Theorie des Nombres des Bordeaux
SN - 2118-8572
TI - Weak multipliers for generalized van der Corput sequences
VL - 24
ER -
TY - JOUR
AU - Edelsbrunner, Herbert
AU - Strelkova, Nataliya
ID - 2912
IS - 6
JF - Uspekhi Mat. Nauk
TI - Configuration space for shortest networks
VL - 67
ER -
TY - CONF
AU - Kroemer, Oliver
AU - Lampert, Christoph
AU - Peters, Jan
ID - 2915
TI - Multi-modal learning for dynamic tactile sensing
ER -
TY - GEN
AB - This paper addresses the problem of approximate MAP-MRF inference in general graphical models. Following [36], we consider a family of linear programming relaxations of the problem where each relaxation is specified by a set of nested pairs of factors for which the marginalization constraint needs to be enforced. We develop a generalization of the TRW-S algorithm [9] for this problem, where we use a decomposition into junction chains, monotonic w.r.t. some ordering on the nodes. This generalizes the monotonic chains in [9] in a natural way. We also show how to deal with nested factors in an efficient way. Experiments show an improvement over min-sum diffusion, MPLP and subgradient ascent algorithms on a number of computer vision and natural language processing problems.
AU - Kolmogorov, Vladimir
AU - Schoenemann, Thomas
ID - 2928
T2 - arXiv
TI - Generalized sequential tree-reweighted message passing
ER -
TY - CONF
AB - In this paper we investigate k-submodular functions. This natural family of discrete functions includes submodular and bisubmodular functions as the special cases k = 1 and k = 2 respectively.
In particular we generalize the known Min-Max-Theorem for submodular and bisubmodular functions. This theorem asserts that the minimum of the (bi)submodular function can be found by solving a maximization problem over a (bi)submodular polyhedron. We define a k-submodular polyhedron, prove a Min-Max-Theorem for k-submodular functions, and give a greedy algorithm to construct the vertices of the polyhedron.
AU - Huber, Anna
AU - Kolmogorov, Vladimir
ID - 2930
TI - Towards minimizing k-submodular functions
VL - 7422
ER -
TY - JOUR
AB - In this paper, we present a new approach for establishing correspondences between sparse image features related by an unknown nonrigid mapping and corrupted by clutter and occlusion, such as points extracted from images of different instances of the same object category. We formulate this matching task as an energy minimization problem by defining an elaborate objective function of the appearance and the spatial arrangement of the features. Optimization of this energy is an instance of graph matching, which is in general an NP-hard problem. We describe a novel graph matching optimization technique, which we refer to as dual decomposition (DD), and demonstrate on a variety of examples that this method outperforms existing graph matching algorithms. In the majority of our examples, DD is able to find the global minimum within a minute. The ability to globally optimize the objective allows us to accurately learn the parameters of our matching model from training examples. We show on several matching tasks that our learned model yields results superior to those of state-of-the-art methods.
AU - Torresani, Lorenzo
AU - Kolmogorov, Vladimir
AU - Rother, Carsten
ID - 2931
IS - 2
JF - IEEE Transactions on Pattern Analysis and Machine Intelligence
TI - A dual decomposition approach to feature correspondence
VL - 35
ER -
TY - CONF
AB - The classical (boolean) notion of refinement for behavioral interfaces of system components is the alternating refinement preorder. In this paper, we define a quantitative measure for interfaces, called interface simulation distance. It makes the alternating refinement preorder quantitative by, intu- itively, tolerating errors (while counting them) in the alternating simulation game. We show that the interface simulation distance satisfies the triangle inequality, that the distance between two interfaces does not increase under parallel composition with a third interface, and that the distance between two interfaces can be bounded from above and below by distances between abstractions of the two interfaces. We illustrate the framework, and the properties of the distances under composition of interfaces, with two case studies.
AU - Cerny, Pavol
AU - Chmelik, Martin
AU - Henzinger, Thomas A
AU - Radhakrishna, Arjun
ID - 2916
T2 - Electronic Proceedings in Theoretical Computer Science
TI - Interface Simulation Distances
VL - 96
ER -
TY - JOUR
AB - The search for extra-terrestrial intelligence (SETI) has been performed principally as a one-way survey, listening of radio frequencies across the Milky Way and other galaxies. However, scientists have engaged in an active messaging only rarely. This suggests the simple rationale that if other civilizations exist and take a similar approach to ours, namely listening but not broadcasting, the result is a silent universe. A simple game theoretical model, the prisoner's dilemma, explains this situation: each player (civilization) can passively search (defect), or actively search and broadcast (cooperate). In order to maximize the payoff (or, equivalently, minimize the risks) the best strategy is not to broadcast. In fact, the active search has been opposed on the basis that it might be dangerous to expose ourselves. However, most of these ideas have not been based on objective arguments, and ignore accounting of the possible gains and losses. Thus, the question stands: should we perform an active search? I develop a game-theoretical framework where civilizations can be of different types, and explicitly apply it to a situation where societies are either interested in establishing a two-way communication or belligerent and in urge to exploit ours. The framework gives a quantitative solution (a mixed-strategy), which is how frequent we should perform the active SETI. This frequency is roughly proportional to the inverse of the risk, and can be extremely small. However, given the immense amount of stars being scanned, it supports active SETI. The model is compared with simulations, and the possible actions are evaluated through the San Marino scale, measuring the risks of messaging.
AU - Vladar, Harold
ID - 2917
IS - 1
JF - International Journal of Astrobiology
TI - The game of active search for extra terrestrial intelligence Breaking the Great Silence
VL - 12
ER -
TY - CONF
AB - The notion of delays arises naturally in many computational models, such as, in the design of circuits, control systems, and dataflow languages. In this work, we introduce automata with delay blocks (ADBs), extending finite state automata with variable time delay blocks, for deferring individual transition output symbols, in a discrete-time setting. We show that the ADB languages strictly subsume the regular languages, and are incomparable in expressive power to the context-free languages. We show that ADBs are closed under union, concatenation and Kleene star, and under intersection with regular languages, but not closed under complementation and intersection with other ADB languages. We show that the emptiness and the membership problems are decidable in polynomial time for ADBs, whereas the universality problem is undecidable. Finally we consider the linear-time model checking problem, i.e., whether the language of an ADB is contained in a regular language, and show that the model checking problem is PSPACE-complete. Copyright 2012 ACM.
AU - Chatterjee, Krishnendu
AU - Henzinger, Thomas A
AU - Prabhu, Vinayak
ID - 2936
T2 - roceedings of the tenth ACM international conference on Embedded software
TI - Finite automata with time delay blocks
ER -
TY - CONF
AB - Developers building cryptography into security-sensitive applications face a daunting task. Not only must they understand the security guarantees delivered by the constructions they choose, they must also implement and combine them correctly and efficiently. Cryptographic compilers free developers from this task by turning high-level specifications of security goals into efficient implementations. Yet, trusting such tools is hard as they rely on complex mathematical machinery and claim security properties that are subtle and difficult to verify. In this paper we present ZKCrypt, an optimizing cryptographic compiler achieving an unprecedented level of assurance without sacrificing practicality for a comprehensive class of cryptographic protocols, known as Zero-Knowledge Proofs of Knowledge. The pipeline of ZKCrypt integrates purpose-built verified compilers and verifying compilers producing formal proofs in the CertiCrypt framework. By combining the guarantees delivered by each stage, ZKCrypt provides assurance that the output implementation securely realizes the abstract proof goal given as input. We report on the main characteristics of ZKCrypt, highlight new definitions and concepts at its foundations, and illustrate its applicability through a representative example of an anonymous credential system.
AU - Almeida, José
AU - Barbosa, Manuel
AU - Bangerter, Endre
AU - Barthe, Gilles
AU - Krenn, Stephan
AU - Béguelin, Santiago
ID - 2937
T2 - Proceedings of the 2012 ACM conference on Computer and communications security
TI - Full proof cryptography: Verifiable compilation of efficient zero-knowledge protocols
ER -
TY - JOUR
AB - Social insects have a very high potential to become invasive pest species. Here, we explore how their social lifestyle and their interaction with parasites may contribute to this invasive success. Similar to solitary species, parasite release followed by the evolution of increased competitive ability can promote establishment of introduced social insect hosts in their introduced range. Genetic bottlenecks during introduction of low numbers of founder individuals decrease the genetic diversity at three levels: the population, the colony and the individual, with the colony level being specific to social insects. Reduced genetic diversity can affect both the individual immune system and the collective colony-level disease defences (social immunity). Still, the dual immune system is likely to make social insects more robust to parasite attack. Changes in social structure from small, family-based, territorially aggressive societies in native populations towards huge networks of cooperating nests (unicoloniality) occur in some invasive social insects, for example, most invasive ants and some termites. Unicoloniality is likely to affect disease dynamics in multiple ways. The free exchange of individuals within the population leads to an increased genetic heterogeneity among individuals of a single nest, thereby decreasing disease transmission. However, the multitude of reproductively active queens per colony buffers the effect of individual diseased queens and their offspring, which may result in a higher level of vertical disease transmission in unicolonial societies. Lastly, unicoloniality provides a competitive advantage over native species, allowing them to quickly become the dominant species in the habitat, which in turn selects for parasite adaptation to this common host genotype and thus eventually a high parasite pressure. Overall, invasions by insect societies are characterized by general features applying to all introduced species, as well as idiosyncrasies that emerge from their social lifestyle. It is important to study these effects in concert to be able to develop efficient management and biocontrol strategies. © 2012 British Ecological Society.
AU - Ugelvig, Line V
AU - Cremer, Sylvia
ID - 2938
IS - 6
JF - Functional Ecology
TI - Effects of social immunity and unicoloniality on host parasite interactions in invasive insect societies
VL - 26
ER -
TY - JOUR
AU - Dolbilin, Nikolai
AU - Edelsbrunner, Herbert
AU - Musin, Oleg
ID - 2941
IS - 4
JF - Russian Mathematical Surveys
TI - On the optimality of functionals over triangulations of Delaunay sets
VL - 67
ER -
TY - CONF
AB - Interface theories provide a formal framework for component-based development of software and hardware which supports the incremental design of systems and the independent implementability of components. These capabilities are ensured through mathematical properties of the parallel composition operator and the refinement relation for components. More recently, a conjunction operation was added to interface theories in order to provide support for handling multiple viewpoints, requirements engineering, and component reuse. Unfortunately, the conjunction operator does not allow independent implementability in general. In this paper, we study conditions that need to be imposed on interface models in order to enforce independent implementability with respect to conjunction. We focus on multiple viewpoint specifications and propose a new compatibility criterion between two interfaces, which we call orthogonality. We show that orthogonal interfaces can be refined separately, while preserving both orthogonality and composability with other interfaces. We illustrate the independent implementability of different viewpoints with a FIFO buffer example.
AU - Henzinger, Thomas A
AU - Nickovic, Dejan
ID - 2942
T2 - Conference proceedings Monterey Workshop 2012
TI - Independent implementability of viewpoints
VL - 7539
ER -
TY - JOUR
AB - We examine whether the Escherichia coli chromosome is folded into a self-adherent nucleoprotein complex, or alternately is a confined but otherwise unconstrained self-avoiding polymer. We address this through in vivo visualization, using an inducible GFP fusion to the nucleoid-associated protein Fis to non-specifically decorate the entire chromosome. For a range of different growth conditions, the chromosome is a compact structure that does not fill the volume of the cell, and which moves from the new pole to the cell centre. During rapid growth, chromosome segregation occurs well before cell division, with daughter chromosomes coupled by a thin inter-daughter filament before complete segregation, whereas during slow growth chromosomes stay adjacent until cell division occurs. Image correlation analysis indicates that sub-nucleoid structure is stable on a 1min timescale, comparable to the timescale for redistribution time measured for GFP-Fis after photobleaching. Optical deconvolution and writhe calculation analysis indicate that the nucleoid has a large-scale coiled organization rather than being an amorphous mass. Our observations are consistent with the chromosome having a self-adherent filament organization.
AU - Hadizadeh Yazdi, Nastaran
AU - Guet, Calin C
AU - Johnson, Reid
AU - Marko, John
ID - 2943
IS - 6
JF - Molecular Microbiology
TI - Variation of the folding and dynamics of the Escherichia coli chromosome with growth conditions
VL - 86
ER -
TY - JOUR
AB - In search of foreign antigens, lymphocytes recirculate from the blood, through lymph nodes, into lymphatics and back to the blood. Dendritic cells also migrate to lymph nodes for optimal interaction with lymphocytes. This continuous trafficking of immune cells into and out of lymph nodes is essential for immune surveillance of foreign invaders. In this article, we review our current understanding of the functions of high endothelial venules (HEVs), stroma and lymphatics in the entry, positioning and exit of immune cells in lymph nodes during homeostasis, and we highlight the unexpected role of dendritic cells in the control of lymphocyte homing through HEVs.
AU - Girard, Jean
AU - Moussion, Christine
AU - Förster, Reinhold
ID - 2945
IS - 11
JF - Nature Reviews Immunology
TI - HEVs, lymphatics and homeostatic immune cell trafficking in lymph nodes
VL - 12
ER -
TY - JOUR
AB - MicroRNAs (miRNAs) are small noncoding RNAs that function in literally all cellular processes. miRNAs interact with Argonaute (Ago) proteins and guide them to specific target sites located in the 3′-untranslated region (3′-UTR) of target mRNAs leading to translational repression and deadenylation-induced mRNA degradation. Most miRNAs are processed from hairpin-structured precursors by the consecutive action of the RNase III enzymes Drosha and Dicer. However, processing of miR-451 is Dicer independent and cleavage is mediated by the endonuclease Ago2. Here we have characterized miR-451 sequence and structure requirements for processing as well as sorting of miRNAs into different Ago proteins. Pre-miR-451 appears to be optimized for Ago2 cleavage and changes result in reduced processing. In addition, we show that the mature miR-451 only associates with Ago2 suggesting that mature miRNAs are not exchanged between different members of the Ago protein family. Based on cloning and deep sequencing of endogenous miRNAs associated with Ago1-3, we do not find evidence for miRNA sorting in human cells. However, Ago identity appears to influence the length of some miRNAs, while others remain unaffected.
AU - Dueck, Anne
AU - Ziegler, Christian
AU - Eichner, Alexander
AU - Berezikov, Eugène
AU - Meister, Gunter
ID - 2946
IS - 19
JF - Nucleic Acids Research
TI - MicroRNAs associated with the different human Argonaute proteins
VL - 40
ER -
TY - CONF
AB - We introduce games with probabilistic uncertainty, a model for controller synthesis in which the controller observes the state through imprecise sensors that provide correct information about the current state with a fixed probability. That is, in each step, the sensors return an observed state, and given the observed state, there is a probability distribution (due to the estimation error) over the actual current state. The controller must base its decision on the observed state (rather than the actual current state, which it does not know). On the other hand, we assume that the environment can perfectly observe the current state. We show that controller synthesis for qualitative ω-regular objectives in our model can be reduced in polynomial time to standard partial-observation stochastic games, and vice-versa. As a consequence we establish the precise decidability frontier for the new class of games, and establish optimal complexity results for all the decidable problems.
AU - Chatterjee, Krishnendu
AU - Chmelik, Martin
AU - Majumdar, Ritankar
ID - 2947
TI - Equivalence of games with probabilistic uncertainty and partial observation games
VL - 7561
ER -
TY - JOUR
AU - Dupret, David
AU - Csicsvari, Jozsef L
ID - 2949
IS - 11
JF - Nature Neuroscience
TI - The medial entorhinal cortex keeps Up
VL - 15
ER -
TY - JOUR
AB - Contractile actomyosin rings drive various fundamental morphogenetic processes ranging from cytokinesis to wound healing. Actomyosin rings are generally thought to function by circumferential contraction. Here, we show that the spreading of the enveloping cell layer (EVL) over the yolk cell during zebrafish gastrulation is driven by a contractile actomyosin ring. In contrast to previous suggestions, we find that this ring functions not only by circumferential contraction but also by a flow-friction mechanism. This generates a pulling force through resistance against retrograde actomyosin flow. EVL spreading proceeds normally in situations where circumferential contraction is unproductive, indicating that the flow-friction mechanism is sufficient. Thus, actomyosin rings can function in epithelial morphogenesis through a combination of cable-constriction and flow-friction mechanisms.
AU - Behrndt, Martin
AU - Salbreux, Guillaume
AU - Campinho, Pedro
AU - Hauschild, Robert
AU - Oswald, Felix
AU - Roensch, Julia
AU - Grill, Stephan
AU - Heisenberg, Carl-Philipp J
ID - 2950
IS - 6104
JF - Science
TI - Forces driving epithelial spreading in zebrafish gastrulation
VL - 338
ER -
TY - JOUR
AB - Differential cell adhesion and cortex tension are thought to drive cell sorting by controlling cell-cell contact formation. Here, we show that cell adhesion and cortex tension have different mechanical functions in controlling progenitor cell-cell contact formation and sorting during zebrafish gastrulation. Cortex tension controls cell-cell contact expansion by modulating interfacial tension at the contact. By contrast, adhesion has little direct function in contact expansion, but instead is needed to mechanically couple the cortices of adhering cells at their contacts, allowing cortex tension to control contact expansion. The coupling function of adhesion is mediated by E-cadherin and limited by the mechanical anchoring of E-cadherin to the cortex. Thus, cell adhesion provides the mechanical scaffold for cell cortex tension to drive cell sorting during gastrulation.
AU - Maître, Jean-Léon
AU - Berthoumieux, Hélène
AU - Krens, Gabriel
AU - Salbreux, Guillaume
AU - Julicher, Frank
AU - Paluch, Ewa
AU - Heisenberg, Carl-Philipp J
ID - 2951
IS - 6104
JF - Science
TI - Adhesion functions in cell sorting by mechanically coupling the cortices of adhering cells
VL - 338
ER -
TY - JOUR
AB - Body axis elongation represents a common and fundamental morphogenetic process in development. A key mechanism triggering body axis elongation without additional growth is convergent extension (CE), whereby a tissue undergoes simultaneous narrowing and extension. Both collective cell migration and cell intercalation are thought to drive CE and are used to different degrees in various species as they elongate their body axis. Here, we provide an overview of CE as a general strategy for body axis elongation and discuss conserved and divergent mechanisms underlying CE among different species.
AU - Tada, Masazumi
AU - Heisenberg, Carl-Philipp J
ID - 2952
IS - 21
JF - Development
TI - Convergent extension Using collective cell migration and cell intercalation to shape embryos
VL - 139
ER -
TY - JOUR
AU - Heisenberg, Carl-Philipp J
AU - Fässler, Reinhard
ID - 2953
IS - 5
JF - Current Opinion in Cell Biology
TI - Cell-cell adhesion and extracellular matrix diversity counts
VL - 24
ER -
TY - JOUR
AB - Spontaneous postsynaptic currents (PSCs) provide key information about the mechanisms of synaptic transmission and the activity modes of neuronal networks. However, detecting spontaneous PSCs in vitro and in vivo has been challenging, because of the small amplitude, the variable kinetics, and the undefined time of generation of these events. Here, we describe a, to our knowledge, new method for detecting spontaneous synaptic events by deconvolution, using a template that approximates the average time course of spontaneous PSCs. A recorded PSC trace is deconvolved from the template, resulting in a series of delta-like functions. The maxima of these delta-like events are reliably detected, revealing the precise onset times of the spontaneous PSCs. Among all detection methods, the deconvolution-based method has a unique temporal resolution, allowing the detection of individual events in high-frequency bursts. Furthermore, the deconvolution-based method has a high amplitude resolution, because deconvolution can substantially increase the signal/noise ratio. When tested against previously published methods using experimental data, the deconvolution-based method was superior for spontaneous PSCs recorded in vivo. Using the high-resolution deconvolution-based detection algorithm, we show that the frequency of spontaneous excitatory postsynaptic currents in dentate gyrus granule cells is 4.5 times higher in vivo than in vitro.
AU - Pernia-Andrade, Alejandro
AU - Goswami, Sarit
AU - Stickler, Yvonne
AU - Fröbe, Ulrich
AU - Schlögl, Alois
AU - Jonas, Peter M
ID - 2954
IS - 7
JF - Biophysical Journal
TI - A deconvolution based method with high sensitivity and temporal resolution for detection of spontaneous synaptic currents in vitro and in vivo
VL - 103
ER -
TY - CONF
AB - We construct a perfectly binding string commitment scheme whose security is based on the learning parity with noise (LPN) assumption, or equivalently, the hardness of decoding random linear codes. Our scheme not only allows for a simple and efficient zero-knowledge proof of knowledge for committed values (essentially a Σ-protocol), but also for such proofs showing any kind of relation amongst committed values, i.e. proving that messages m_0,...,m_u, are such that m_0=C(m_1,...,m_u) for any circuit C.
To get soundness which is exponentially small in a security parameter t, and when the zero-knowledge property relies on the LPN problem with secrets of length l, our 3 round protocol has communication complexity O(t|C|l log(l)) and computational complexity of O(t|C|l) bit operations. The hidden constants are small, and the computation consists mostly of computing inner products of bit-vectors.
AU - Jain, Abhishek
AU - Krenn, Stephan
AU - Pietrzak, Krzysztof Z
AU - Tentes, Aris
ED - Wang, Xiaoyun
ED - Sako, Kazue
ID - 2974
TI - Commitments and efficient zero knowledge proofs from learning parity with noise
VL - 7658
ER -
TY - JOUR
AB - The activity of hippocampal pyramidal cells reflects both the current position of the animal and information related to its current behavior. Here we investigated whether single hippocampal neurons can encode several independent features defining trials during a memory task. We also tested whether task-related information is represented by partial remapping of the place cell population or, instead, via firing rate modulation of spatially stable place cells. To address these two questions, the activity of hippocampal neurons was recorded in rats performing a conditional discrimination task on a modified T-maze in which the identity of a food reward guided behavior. When the rat was on the central arm of the maze, the firing rate of pyramidal cells changed depending on two independent factors: (1) the identity of the food reward given to the animal and (2) the previous location of the animal on the maze. Importantly, some pyramidal cells encoded information relative to both factors. This trial-type specific and retrospective coding did not interfere with the spatial representation of the maze: hippocampal cells had stable place fields and their theta-phase precession profiles were unaltered during the task, indicating that trial-related information was encoded via rate remapping. During error trials, encoding of both trial-related information and spatial location was impaired. Finally, we found that pyramidal cells also encode trial-related information via rate remapping during the continuous version of the rewarded alternation task without delays. These results suggest that hippocampal neurons can encode several task-related cognitive aspects via rate remapping.
AU - Allen, Kevin
AU - Rawlins, J Nick
AU - Bannerman, David
AU - Csicsvari, Jozsef L
ID - 2958
IS - 42
JF - Journal of Neuroscience
TI - Hippocampal place cells can encode multiple trial-dependent features through rate remapping
VL - 32
ER -
TY - JOUR
AB - We study maximum likelihood estimation in Gaussian graphical models from a geometric point of view. An algebraic elimination criterion allows us to find exact lower bounds on the number of observations needed to ensure that the maximum likelihood estimator (MLE) exists with probability one. This is applied to bipartite graphs, grids and colored graphs. We also study the ML degree, and we present the first instance of a graph for which the MLE exists with probability one, even when the number of observations equals the treewidth.
AU - Uhler, Caroline
ID - 2959
IS - 1
JF - Annals of Statistics
TI - Geometry of maximum likelihood estimation in Gaussian graphical models
VL - 40
ER -
TY - JOUR
AB - The choice of summary statistics is a crucial step in approximate Bayesian computation (ABC). Since statistics are often not sufficient, this choice involves a trade-off between loss of information and reduction of dimensionality. The latter may increase the efficiency of ABC. Here, we propose an approach for choosing summary statistics based on boosting, a technique from the machine learning literature. We consider different types of boosting and compare them to partial least squares regression as an alternative. To mitigate the lack of sufficiency, we also propose an approach for choosing summary statistics locally, in the putative neighborhood of the true parameter value. We study a demographic model motivated by the re-introduction of Alpine ibex (Capra ibex) into the Swiss Alps. The parameters of interest are the mean and standard deviation across microsatellites of the scaled ancestral mutation rate (θanc = 4 Ne u), and the proportion of males obtaining access to matings per breeding season (ω). By simulation, we assess the properties of the posterior distribution obtained with the various methods. According to our criteria, ABC with summary statistics chosen locally via boosting with the L2-loss performs best. Applying that method to the ibex data, we estimate θanc ≈ 1.288, and find that most of the variation across loci of the ancestral mutation rate u is between 7.7×10−4 and 3.5×10−3 per locus per generation. The proportion of males with access to matings is estimated to ω ≈ 0.21, which is in good agreement with recent independent estimates.
AU - Aeschbacher, Simon
AU - Beaumont, Mark
AU - Futschik, Andreas
ID - 2962
IS - 3
JF - Genetics
TI - A novel approach for choosing summary statistics in approximate Bayesian computation
VL - 192
ER -
TY - JOUR
AB - Zebra finches are an ubiquitous model system for the study of vocal learning in animal communication. Their song has been well described, but its possible function(s) in social communication are only partly understood. The so-called ‘directed song’ is a high-intensity, high-performance song given during courtship in close proximity to the female, which is known to mediate mate choice and mating. However, this singing mode constitutes only a fraction of zebra finch males’ prolific song output. Potential communicative functions of their second, ‘undirected’ singing mode remain unresolved in the face of contradicting reports of both facilitating and inhibiting effects of social company on singing. We addressed this issue by experimentally manipulating social contexts in a within-subject design, comparing a solo versus male or female only company condition, each lasting for 24 hours. Males’ total song output was significantly higher when a conspecific was in audible and visible distance than when they were alone. Male and female company had an equally facilitating effect on song output. Our findings thus indicate that singing motivation is facilitated rather than inhibited by social company, suggesting that singing in zebra finches might function both in inter- and intrasexual communication.
AU - Jesse, Fabienne
AU - Riebel, Katharina
ID - 2963
IS - 3
JF - Behavioural Processes
TI - Social facilitation of male song by male and female conspecifics in the zebra finch, Taeniopygia guttata
VL - 91
ER -
TY - JOUR
AB - Little is known about the stability of trophic relationships in complex natural communities over evolutionary timescales. Here, we use sequence data from 18 nuclear loci to reconstruct and compare the intraspecific histories of major Pleistocene refugial populations in the Middle East, the Balkans and Iberia in a guild of four Chalcid parasitoids (Cecidostiba fungosa, Cecidostiba semifascia, Hobbya stenonota and Mesopolobus amaenus) all attacking Cynipid oak galls. We develop a likelihood method to numerically estimate models of divergence between three populations from multilocus data. We investigate the power of this framework on simulated data, and-using triplet alignments of intronic loci-quantify the support for all possible divergence relationships between refugial populations in the four parasitoids. Although an East to West order of population divergence has highest support in all but one species, we cannot rule out alternative population tree topologies. Comparing the estimated times of population splits between species, we find that one species, M. amaenus, has a significantly older history than the rest of the guild and must have arrived in central Europe at least one glacial cycle prior to other guild members. This suggests that although all four species may share a common origin in the East, they expanded westwards into Europe at different times. © 2012 Blackwell Publishing Ltd.
AU - Lohse, Konrad
AU - Barton, Nicholas H
AU - Melika, George
AU - Stone, Graham
ID - 2968
IS - 18
JF - Molecular Ecology
TI - A likelihood based comparison of population histories in a parasitoid guild
VL - 21
ER -
TY - JOUR
AB - The coupling between presynaptic Ca^(2+) channels and Ca^(2+) sensors of exocytosis is a key determinant of synaptic transmission. Evoked release from parvalbumin (PV)-expressing interneurons is triggered by nanodomain coupling of P/Q-type Ca^(2+) channels, whereas release from cholecystokinin (CCK)-containing interneurons is generated by microdomain coupling of N-type channels. Nanodomain coupling has several functional advantages, including speed and efficacy of transmission. One potential disadvantage is that stochastic
opening of presynaptic Ca^(2+) channels may trigger spontaneous transmitter release. We addressed this possibility in rat hippocampal
granule cells, which receive converging inputs from different inhibitory sources. Both reduction of extracellular Ca^(2+) concentration and the unselective Ca^(2+) channel blocker Cd^(2+) reduced the frequency of miniature IPSCs (mIPSCs) in granule cells by ~50%, suggesting that the opening of presynaptic Ca^(2+) channels contributes to spontaneous release. Application of the selective P/Q-type Ca^(2+) channel blocker
ω-agatoxin IVa had no detectable effects, whereas both the N-type blocker ω-conotoxin GVIa and the L-type blocker nimodipine reduced
mIPSC frequency. Furthermore, both the fast Ca^(2+) chelator BAPTA-AM and the slow chelator EGTA-AM reduced the mIPSC frequency,
suggesting that Ca^(2+)-dependent spontaneous release is triggered by microdomain rather than nanodomain coupling. The CB_(1) receptor
agonist WIN 55212-2 also decreased spontaneous release; this effect was occluded by prior application of ω-conotoxin GVIa, suggesting that a major fraction of Ca^(2+)-dependent spontaneous release was generated at the terminals of CCK-expressing interneurons. Tonic inhibition generated by spontaneous opening of presynaptic N- and L-type Ca^(2+) channels may be important for hippocampal information processing.
AU - Goswami, Sarit
AU - Bucurenciu, Iancu
AU - Jonas, Peter M
ID - 2969
IS - 41
JF - Journal of Neuroscience
TI - Miniature IPSCs in hippocampal granule cells are triggered by voltage-gated Ca^(2+) channels via microdomain coupling
VL - 32
ER -
TY - JOUR
AB - Morphogen gradients regulate the patterning and growth of many tissues, hence a key question is how they are established and maintained during development. Theoretical descriptions have helped to explain how gradient shape is controlled by the rates of morphogen production, spreading and degradation. These effective rates have been measured using fluorescence recovery after photobleaching (FRAP) and photoactivation. To unravel which molecular events determine the effective rates, such tissue-level assays have been combined with genetic analysis, high-resolution assays, and models that take into account interactions with receptors, extracellular components and trafficking. Nevertheless, because of the natural and experimental data variability, and the underlying assumptions of transport models, it remains challenging to conclusively distinguish between cellular mechanisms.
AU - Kicheva, Anna
AU - Bollenbach, Mark Tobias
AU - Wartlick, Ortrud
AU - Julicher, Frank
AU - Gonzalez Gaitan, Marcos
ID - 2970
IS - 6
JF - Current Opinion in Genetics & Development
TI - Investigating the principles of morphogen gradient formation: from tissues to cells
VL - 22
ER -
TY - CONF
AB - We study the task of interactive semantic labeling of a segmentation hierarchy. To this end we propose a framework interleaving two components: an automatic labeling step, based on a Conditional Random Field whose dependencies are defined by the inclusion tree of the segmentation hierarchy, and an interaction step that integrates incremental input from a human user. Evaluated on two distinct datasets, the proposed interactive approach efficiently integrates human interventions and illustrates the advantages of structured prediction in an interactive framework.
AU - Zankl, Georg
AU - Haxhimusa, Yll
AU - Ion, Adrian
ID - 2971
TI - Interactive labeling of image segmentation hierarchies
VL - 7476
ER -
TY - JOUR
AB - Dieser Artikel soll die sechs verschiedenen Creative Commons Lizenzen erläutern und ihre Bedeutung im Rahmen des wissenschaftlichen Publizierens und des Open Access erklären (CC-BY, CC-BY-SA, CC-BY-NC, CC-BY-ND, CC-BYNC-SA, CC-BY-NC-ND).
AU - Danowski, Patrick
ID - 2965
IS - 2
JF - Mitteilungen der Vereinigung Österreichischer Bibliothekarinnen & Bibliothekare
TI - Kontext Open Access: Creative Commons
VL - 65
ER -
TY - JOUR
AB - Background: The outcome of male-male competition can be predicted from the relative fighting qualities of the opponents, which often depend on their age. In insects, freshly emerged and still sexually inactive males are morphologically indistinct from older, sexually active males. These young inactive males may thus be easy targets for older males if they cannot conceal themselves from their attacks. The ant Cardiocondyla obscurior is characterised by lethal fighting between wingless (" ergatoid" ) males. Here, we analyse for how long young males are defenceless after eclosion, and how early adult males can detect the presence of rival males.Results: We found that old ergatoid males consistently won fights against ergatoid males younger than two days. Old males did not differentiate between different types of unpigmented pupae several days before emergence, but had more frequent contact to ready-to-eclose pupae of female sexuals and winged males than of workers and ergatoid males. In rare cases, old ergatoid males displayed alleviated biting of pigmented ergatoid male pupae shortly before adult eclosion, as well as copulation attempts to dark pupae of female sexuals and winged males. Ergatoid male behaviour may be promoted by a closer similarity of the chemical profile of ready-to-eclose pupae to the profile of adults than that of young pupae several days prior to emergence.Conclusion: Young ergatoid males of C. obscurior would benefit greatly by hiding their identity from older, resident males, as they are highly vulnerable during the first two days of their adult lives. In contrast to the winged males of the same species, which are able to prevent ergatoid male attacks by chemical female mimicry, young ergatoids do not seem to be able to produce a protective chemical profile. Conflicts in male-male competition between ergatoid males of different age thus seem to be resolved in favour of the older males. This might represent selection at the colony level rather than the individual level. © 2012 Cremer et al.; licensee BioMed Central Ltd.
AU - Cremer, Sylvia
AU - Suefuji, Masaki
AU - Schrempf, Alexandra
AU - Heinze, Jürgen
ID - 2966
JF - BMC Ecology
TI - The dynamics of male-male competition in Cardiocondyla obscurior ants
VL - 12
ER -
TY - JOUR
AB - We consider the problem of minimizing a function represented as a sum of submodular terms. We assume each term allows an efficient computation of exchange capacities. This holds, for example, for terms depending on a small number of variables, or for certain cardinality-dependent terms. A naive application of submodular minimization algorithms would not exploit the existence of specialized exchange capacity subroutines for individual terms. To overcome this, we cast the problem as a submodular flow (SF) problem in an auxiliary graph in such a way that applying most existing SF algorithms would rely only on these subroutines. We then explore in more detail Iwata's capacity scaling approach for submodular flows (Iwata 1997 [19]). In particular, we show how to improve its complexity in the case when the function contains cardinality-dependent terms.
AU - Kolmogorov, Vladimir
ID - 3117
IS - 15
JF - Discrete Applied Mathematics
TI - Minimizing a sum of submodular functions
VL - 160
ER -
TY - JOUR
AB - We present a method for recovering a temporally coherent, deforming triangle mesh with arbitrarily changing topology from an incoherent sequence of static closed surfaces. We solve this problem using the surface geometry alone, without any prior information like surface templates or velocity fields. Our system combines a proven strategy for triangle mesh improvement, a robust multi-resolution non-rigid registration routine, and a reliable technique for changing surface mesh topology. We also introduce a novel topological constraint enforcement algorithm to ensure that the output and input always have similar topology. We apply our technique to a series of diverse input data from video reconstructions, physics simulations, and artistic morphs. The structured output of our algorithm allows us to efficiently track information like colors and displacement maps, recover velocity information, and solve PDEs on the mesh as a post process.
AU - Bojsen-Hansen, Morten
AU - Li, Hao
AU - Wojtan, Christopher J
ID - 3118
IS - 4
JF - ACM Transactions on Graphics
TI - Tracking surfaces with evolving topology
VL - 31
ER -
TY - CONF
AB - We present an approach for artist-directed animation of liquids using multiple levels of control over the simulation, ranging from the overall tracking of desired shapes to highly detailed secondary effects such as dripping streams, separating sheets of fluid, surface waves and ripples. The first portion of our technique is a volume preserving morph that allows the animator to produce a plausible fluid-like motion from a sparse set of control meshes. By rasterizing the resulting control meshes onto the simulation grid, the mesh velocities act as boundary conditions during the projection step of the fluid simulation. We can then blend this motion together with uncontrolled fluid velocities to achieve a more relaxed control over the fluid that captures natural inertial effects. Our method can produce highly detailed liquid surfaces with control over sub-grid details by using a mesh-based surface tracker on top of a coarse grid-based fluid simulation. We can create ripples and waves on the fluid surface attracting the surface mesh to the control mesh with spring-like forces and also by running a wave simulation over the surface mesh. Our video results demonstrate how our control scheme can be used to create animated characters and shapes that are made of water.
AU - Raveendran, Karthik
AU - Thuerey, Nils
AU - Wojtan, Christopher J
AU - Turk, Greg
ID - 3119
T2 - Proceedings of the ACM SIGGRAPH/Eurographics Symposium on Computer Animation
TI - Controlling liquids using meshes
ER -
TY - JOUR
AB - We introduce a strategy based on Kustin-Miller unprojection that allows us to construct many hundreds of Gorenstein codimension 4 ideals with 9 × 16 resolutions (that is, nine equations and sixteen first syzygies). Our two basic games are called Tom and Jerry; the main application is the biregular construction of most of the anticanonically polarised Mori Fano 3-folds of Altinok's thesis. There are 115 cases whose numerical data (in effect, the Hilbert series) allow a Type I projection. In every case, at least one Tom and one Jerry construction works, providing at least two deformation families of quasismooth Fano 3-folds having the same numerics but different topology. © 2012 Copyright Foundation Compositio Mathematica.
AU - Brown, Gavin
AU - Kerber, Michael
AU - Reid, Miles
ID - 3120
IS - 4
JF - Compositio Mathematica
TI - Fano 3 folds in codimension 4 Tom and Jerry Part I
VL - 148
ER -
TY - JOUR
AB - Voltage-activated Ca(2+) channels (VACCs) mediate Ca(2+) influx to trigger action potential-evoked neurotransmitter release, but the mechanism by which Ca(2+) regulates spontaneous transmission is unclear. We found that VACCs are the major physiological triggers for spontaneous release at mouse neocortical inhibitory synapses. Moreover, despite the absence of a synchronizing action potential, we found that spontaneous fusion of a GABA-containing vesicle required the activation of multiple tightly coupled VACCs of variable type.
AU - Williams, Courtney
AU - Chen, Wenyan
AU - Lee, Chia
AU - Yaeger, Daniel
AU - Vyleta, Nicholas
AU - Smith, Stephen
ID - 3121
IS - 9
JF - Nature Neuroscience
TI - Coactivation of multiple tightly coupled calcium channels triggers spontaneous release of GABA
VL - 15
ER -