TY - JOUR
AB - Coalescent simulation has become an indispensable tool in population genetics and many complex evolutionary scenarios have been incorporated into the basic algorithm. Despite many years of intense interest in spatial structure, however, there are no available methods to simulate the ancestry of a sample of genes that occupy a spatial continuum. This is mainly due to the severe technical problems encountered by the classical model of isolation
by distance. A recently introduced model solves these technical problems and provides a solid theoretical basis for the study of populations evolving in continuous space. We present a detailed algorithm to simulate the coalescent process in this model, and provide an efficient implementation of a generalised version of this algorithm as a freely available Python module.
AU - Kelleher, Jerome
AU - Barton, Nicholas H
AU - Etheridge, Alison
ID - 2910
IS - 7
JF - Bioinformatics
TI - Coalescent simulation in continuous space
VL - 29
ER -
TY - JOUR
AB - The ability of an organism to distinguish between various stimuli is limited by the structure and noise in the population code of its sensory neurons. Here we infer a distance measure on the stimulus space directly from the recorded activity of 100 neurons in the salamander retina. In contrast to previously used measures of stimulus similarity, this "neural metric" tells us how distinguishable a pair of stimulus clips is to the retina, based on the similarity between the induced distributions of population responses. We show that the retinal distance strongly deviates from Euclidean, or any static metric, yet has a simple structure: we identify the stimulus features that the neural population is jointly sensitive to, and show the support-vector-machine- like kernel function relating the stimulus and neural response spaces. We show that the non-Euclidean nature of the retinal distance has important consequences for neural decoding.
AU - Tkacik, Gasper
AU - Granot Atedgi, Einat
AU - Segev, Ronen
AU - Schneidman, Elad
ID - 2913
IS - 5
JF - Physical Review Letters
TI - Retinal metric: a stimulus distance measure derived from population neural responses
VL - 110
ER -
TY - JOUR
AB - The scale invariance of natural images suggests an analogy to the statistical mechanics of physical systems at a critical point. Here we examine the distribution of pixels in small image patches and show how to construct the corresponding thermodynamics. We find evidence for criticality in a diverging specific heat, which corresponds to large fluctuations in how "surprising" we find individual images, and in the quantitative form of the entropy vs energy. We identify special image configurations as local energy minima and show that average patches within each basin are interpretable as lines and edges in all orientations.
AU - Stephens, Greg
AU - Mora, Thierry
AU - Tkacik, Gasper
AU - Bialek, William
ID - 2914
IS - 1
JF - Physical Review Letters
TI - Statistical thermodynamics of natural images
VL - 110
ER -
TY - JOUR
AB - Oriented mitosis is essential during tissue morphogenesis. The Wnt/planar cell polarity (Wnt/PCP) pathway orients mitosis in a number of developmental systems, including dorsal epiblast cell divisions along the animal-vegetal (A-V) axis during zebrafish gastrulation. How Wnt signalling orients the mitotic plane is, however, unknown. Here we show that, in dorsal epiblast cells, anthrax toxin receptor 2a (Antxr2a) accumulates in a polarized cortical cap, which is aligned with the embryonic A-V axis and forecasts the division plane. Filamentous actin (F-actin) also forms an A-V polarized cap, which depends on Wnt/PCP and its effectors RhoA and Rock2. Antxr2a is recruited to the cap by interacting with actin. Antxr2a also interacts with RhoA and together they activate the diaphanous-related formin zDia2. Mechanistically, Antxr2a functions as a Wnt-dependent polarized determinant, which, through the action of RhoA and zDia2, exerts torque on the spindle to align it with the A-V axis.
AU - Castanon, Irinka
AU - Abrami, Laurence
AU - Holtzer, Laurent
AU - Heisenberg, Carl-Philipp J
AU - Van Der Goot, Françoise
AU - González Gaitán, Marcos
ID - 2918
IS - 1
JF - Nature Cell Biology
TI - Anthrax toxin receptor 2a controls mitotic spindle positioning
VL - 15
ER -
TY - JOUR
AB - The distribution of the phytohormone auxin regulates many aspects of plant development including growth response to gravity. Gravitropic root curvature involves coordinated and asymmetric cell elongation between the lower and upper side of the root, mediated by differential cellular auxin levels. The asymmetry in the auxin distribution is established and maintained by a spatio-temporal regulation of the PIN-FORMED (PIN) auxin transporter activity. We provide novel insights into the complex regulation of PIN abundance and activity during root gravitropism. We show that PIN2 turnover is differentially regulated on the upper and lower side of gravistimulated roots by distinct but partially overlapping auxin feedback mechanisms. In addition to regulating transcription and clathrin-mediated internalization, auxin also controls PIN abundance at the plasma membrane by promoting their vacuolar targeting and degradation. This effect of elevated auxin levels requires the activity of SKP-Cullin-F-box TIR1/AFB (SCF TIR1/AFB)-dependent pathway. Importantly, also suboptimal auxin levels mediate PIN degradation utilizing the same signalling pathway. These feedback mechanisms are functionally important during gravitropic response and ensure fine-tuning of auxin fluxes for maintaining as well as terminating asymmetric growth.
AU - Baster, Pawel
AU - Robert, Stéphanie
AU - Kleine Vehn, Jürgen
AU - Vanneste, Steffen
AU - Kania, Urszula
AU - Grunewald, Wim
AU - De Rybel, Bert
AU - Beeckman, Tom
AU - Friml, Jirí
ID - 2919
IS - 2
JF - EMBO Journal
TI - SCF^TIR1 AFB-auxin signalling regulates PIN vacuolar trafficking and auxin fluxes during root gravitropism
VL - 32
ER -
TY - JOUR
AB - Cell polarisation in development is a common and fundamental process underlying embryo patterning and morphogenesis, and has been extensively studied over the past years. Our current knowledge of cell polarisation in development is predominantly based on studies that have analysed polarisation of single cells, such as eggs, or cellular aggregates with a stable polarising interface, such as cultured epithelial cells (St Johnston and Ahringer, 2010). However, in embryonic development, particularly of vertebrates, cell polarisation processes often encompass large numbers of cells that are placed within moving and proliferating tissues, and undergo mesenchymal-to-epithelial transitions with a highly complex spatiotemporal choreography. How such intricate cell polarisation processes in embryonic development are achieved has only started to be analysed. By using live imaging of neurulation in the transparent zebrafish embryo, Buckley et al (2012) now describe a novel polarisation strategy by which cells assemble an apical domain in the part of their cell body that intersects with the midline of the forming neural rod. This mechanism, along with the previously described mirror-symmetric divisions (Tawk et al, 2007), is thought to trigger formation of both neural rod midline and lumen.
AU - Compagnon, Julien
AU - Heisenberg, Carl-Philipp J
ID - 2920
IS - 1
JF - EMBO Journal
TI - Neurulation coordinating cell polarisation and lumen formation
VL - 32
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 - CONF
AB - A chain rule for an entropy notion H(.) states that the entropy H(X) of a variable X decreases by at most l if conditioned on an l-bit string A, i.e., H(X|A)>= H(X)-l. More generally, it satisfies a chain rule for conditional entropy if H(X|Y,A)>= H(X|Y)-l.
All natural information theoretic entropy notions we are aware of (like Shannon or min-entropy) satisfy some kind of chain rule for conditional entropy. Moreover, many computational entropy notions (like Yao entropy, unpredictability entropy and several variants of HILL entropy) satisfy the chain rule for conditional entropy, though here not only the quantity decreases by l, but also the quality of the entropy decreases exponentially in l. However, for
the standard notion of conditional HILL entropy (the computational equivalent of min-entropy) the existence of such a rule was unknown so far.
In this paper, we prove that for conditional HILL entropy no meaningful chain rule exists, assuming the existence of one-way permutations: there exist distributions X,Y,A, where A is a distribution over a single bit, but $H(X|Y)>>H(X|Y,A)$, even if we simultaneously allow for a massive degradation in the quality of the entropy.
The idea underlying our construction is based on a surprising connection between the chain rule for HILL entropy and deniable encryption.
AU - Krenn, Stephan
AU - Pietrzak, Krzysztof Z
AU - Wadia, Akshay
ED - Sahai, Amit
ID - 2940
TI - A counterexample to the chain rule for conditional HILL entropy, and what deniable encryption has to do with it
VL - 7785
ER -
TY - CONF
AB - Many visual datasets are traditionally used to analyze the performance of different learning techniques. The evaluation is usually done within each dataset, therefore it is questionable if such results are a reliable indicator of true generalization ability. We propose here an algorithm to exploit the existing data resources when learning on a new multiclass problem. Our main idea is to identify an image representation that decomposes orthogonally into two subspaces: a part specific to each dataset, and a part generic to, and therefore shared between, all the considered source sets. This allows us to use the generic representation as un-biased reference knowledge for a novel classification task. By casting the method in the multi-view setting, we also make it possible to use different features for different databases. We call the algorithm MUST, Multitask Unaligned Shared knowledge Transfer. Through extensive experiments on five public datasets, we show that MUST consistently improves the cross-datasets generalization performance.
AU - Tommasi, Tatiana
AU - Quadrianto, Novi
AU - Caputo, Barbara
AU - Lampert, Christoph
ID - 2948
TI - Beyond dataset bias: Multi-task unaligned shared knowledge transfer
VL - 7724
ER -
TY - JOUR
AB - Multithreaded programs coordinate their interaction through synchronization primitives like mutexes and semaphores, which are managed by an OS-provided resource manager. We propose algorithms for the automatic construction of code-aware resource managers for multithreaded embedded applications. Such managers use knowledge about the structure and resource usage (mutex and semaphore usage) of the threads to guarantee deadlock freedom and progress while managing resources in an efficient way. Our algorithms compute managers as winning strategies in certain infinite games, and produce a compact code description of these strategies. We have implemented the algorithms in the tool Cynthesis. Given a multithreaded program in C, the tool produces C code implementing a code-aware resource manager. We show in experiments that Cynthesis produces compact resource managers within a few minutes on a set of embedded benchmarks with up to 6 threads. © 2012 Springer Science+Business Media, LLC.
AU - Chatterjee, Krishnendu
AU - De Alfaro, Luca
AU - Faella, Marco
AU - Majumdar, Ritankar
AU - Raman, Vishwanath
ID - 3116
IS - 2
JF - Formal Methods in System Design
TI - Code aware resource management
VL - 42
ER -
TY - JOUR
AB - Cells in a developing embryo have no direct way of "measuring" their physical position. Through a variety of processes, however, the expression levels of multiple genes come to be correlated with position, and these expression levels thus form a code for "positional information." We show how to measure this information, in bits, using the gap genes in the Drosophila embryo as an example. Individual genes carry nearly two bits of information, twice as much as expected if the expression patterns consisted only of on/off domains separated by sharp boundaries. Taken together, four gap genes carry enough information to define a cell's location with an error bar of ~1% along the anterior-posterior axis of the embryo. This precision is nearly enough for each cell to have a unique identity, which is the maximum information the system can use, and is nearly constant along the length of the embryo. We argue that this constancy is a signature of optimality in the transmission of information from primary morphogen inputs to the output of the gap gene network.
AU - Dubuis, Julien
AU - Tkacik, Gasper
AU - Wieschaus, Eric
AU - Gregor, Thomas
AU - Bialek, William
ID - 3261
IS - 41
JF - PNAS
TI - Positional information, in bits
VL - 110
ER -
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 - 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 - JOUR
AB - Understanding the relative importance of heterosis and outbreeding depression over multiple generations is a key question in evolutionary biology and is essential for identifying appropriate genetic sources for population and ecosystem restoration. Here we use 2455 experimental crosses between 12 population pairs of the rare perennial plant Rutidosis leptorrhynchoides (Asteraceae) to investigate the multi-generational (F1, F2, F3) fitness outcomes of inter-population hybridization. We detected no evidence of outbreeding depression, with inter-population hybrids and backcrosses showing either similar fitness or significant heterosis for fitness components across the three generations. Variation in heterosis among population pairs was best explained by characteristics of the foreign source or home population, and was greatest when the source population was large, with high genetic diversity and low inbreeding, and the home population was small and inbred. Our results indicate that the primary consideration for maximizing progeny fitness following population augmentation or restoration is the use of seed from large, genetically diverse populations.
AU - Pickup, Melinda
AU - Field, David
AU - Rowell, David
AU - Young, Andrew
ID - 450
IS - 1750
JF - Proceedings of the Royal Society of London Series B Biological Sciences
TI - Source population characteristics affect heterosis following genetic rescue of fragmented plant populations
VL - 280
ER -
TY - JOUR
AB - Maternal exposure to infection occurring mid-gestation produces a three-fold increase in the risk of schizophrenia in the offspring. The critical initiating factor appears to be the maternal immune activation (MIA) that follows infection. This process can be induced in rodents by exposure of pregnant dams to the viral mimic Poly I:C, which triggers an immune response that results in structural, functional, behavioral, and electrophysiological phenotypes in the adult offspring that model those seen in schizophrenia. We used this model to explore the role of synchronization in brain neural networks, a process thought to be dysfunctional in schizophrenia and previously associated with positive, negative, and cognitive symptoms of schizophrenia. Exposure of pregnant dams to Poly I:C on GD15 produced an impairment in long-range neural synchrony in adult offspring between two regions implicated in schizophrenia pathology; the hippocampus and the medial prefrontal cortex (mPFC). This reduction in synchrony was ameliorated by acute doses of the antipsychotic clozapine. MIA animals have previously been shown to have impaired pre-pulse inhibition (PPI), a gold-standard measure of schizophrenia-like deficits in animal models. Our data showed that deficits in synchrony were positively correlated with the impairments in PPI. Subsequent analysis of LFP activity during the PPI response also showed that reduced coupling between the mPFC and the hippocampus following processing of the pre-pulse was associated with reduced PPI. The ability of the MIA intervention to model neurodevelopmental aspects of schizophrenia pathology provides a useful platform from which to investigate the ontogeny of aberrant synchronous processes. Further, the way in which the model expresses translatable deficits such as aberrant synchrony and reduced PPI will allow researchers to explore novel intervention strategies targeted to these changes.
AU - Dickerson, Desiree
AU - Bilkey, David
ID - 476
IS - DEC
JF - Frontiers in Behavioral Neuroscience
TI - Aberrant neural synchrony in the maternal immune activation model: Using translatable measures to explore targeted interventions
VL - 7
ER -
TY - JOUR
AB - Exposure of an isogenic bacterial population to a cidal antibiotic typically fails to eliminate a small fraction of refractory cells. Historically, fractional killing has been attributed to infrequently dividing or nondividing "persisters." Using microfluidic cultures and time-lapse microscopy, we found that Mycobacterium smegmatis persists by dividing in the presence of the drug isoniazid (INH). Although persistence in these studies was characterized by stable numbers of cells, this apparent stability was actually a dynamic state of balanced division and death. Single cells expressed catalase-peroxidase (KatG), which activates INH, in stochastic pulses that were negatively correlated with cell survival. These behaviors may reflect epigenetic effects, because KatG pulsing and death were correlated between sibling cells. Selection of lineages characterized by infrequent KatG pulsing could allow nonresponsive adaptation during prolonged drug exposure.
AU - Wakamoto, Yurichi
AU - Dhar, Neraaj
AU - Chait, Remy P
AU - Schneider, Katrin
AU - Signorino Gelo, François
AU - Leibler, Stanislas
AU - Mckinney, John
ID - 499
IS - 6115
JF - Science
TI - Dynamic persistence of antibiotic-stressed mycobacteria
VL - 339
ER -
TY - JOUR
AB - Background: Reassortment between the RNA segments encoding haemagglutinin (HA) and neuraminidase (NA), the major antigenic influenza proteins, produces viruses with novel HA and NA subtype combinations and has preceded the emergence of pandemic strains. It has been suggested that productive viral infection requires a balance in the level of functional activity of HA and NA, arising from their closely interacting roles in the viral life cycle, and that this functional balance could be mediated by genetic changes in the HA and NA. Here, we investigate how the selective pressure varies for H7 avian influenza HA on different NA subtype backgrounds. Results: By extending Bayesian stochastic mutational mapping methods to calculate the ratio of the rate of non-synonymous change to the rate of synonymous change (d N/d S), we found the average d N/d S across the avian influenza H7 HA1 region to be significantly greater on an N2 NA subtype background than on an N1, N3 or N7 background. Observed differences in evolutionary rates of H7 HA on different NA subtype backgrounds could not be attributed to underlying differences between avian host species or virus pathogenicity. Examination of d N/d S values for each subtype on a site-by-site basis indicated that the elevated d N/d S on the N2 NA background was a result of increased selection, rather than a relaxation of selective constraint. Conclusions: Our results are consistent with the hypothesis that reassortment exposes influenza HA to significant changes in selective pressure through genetic interactions with NA. Such epistatic effects might be explicitly accounted for in future models of influenza evolution.
AU - Ward, Melissa
AU - Lycett, Samantha
AU - Avila, Dorita
AU - Bollback, Jonathan P
AU - Leigh Brown, Andrew
ID - 500
IS - 1
JF - BMC Evolutionary Biology
TI - Evolutionary interactions between haemagglutinin and neuraminidase in avian influenza
VL - 13
ER -
TY - JOUR
AB - All known species of extant tapirs are allopatric: 1 in southeastern Asia and 3 in Central and South America. The fossil record for tapirs, however, is much wider in geographical range, including Europe, Asia, and North and South America, going back to the late Oligocene, making the present distribution a relict of the original one. We here describe a new species of living Tapirus from the Amazon rain forest, the 1st since T. bairdii Gill, 1865, and the 1st new Perissodactyla in more than 100 years, from both morphological and molecular characters. It is shorter in stature than T. terrestris (Linnaeus, 1758) and has distinctive skull morphology, and it is basal to the clade formed by T. terrestris and T. pinchaque (Roulin, 1829). This highlights the unrecognized biodiversity in western Amazonia, where the biota faces increasing threats. Local peoples have long recognized our new species, suggesting a key role for traditional knowledge in understanding the biodiversity of the region.
AU - Cozzuol, Mario
AU - Clozato, Camila
AU - Holanda, Elizete
AU - Rodrigues, Flávio
AU - Nienow, Samuel
AU - De Thoisy, Benoit
AU - Fernandes Redondo, Rodrigo A
AU - Santos, Fabrício
ID - 501
IS - 6
JF - Journal of Mammalogy
TI - A new species of tapir from the Amazon
VL - 94
ER -
TY - JOUR
AB - Blind signatures allow users to obtain signatures on messages hidden from the signer; moreover, the signer cannot link the resulting message/signature pair to the signing session. This paper presents blind signature schemes, in which the number of interactions between the user and the signer is minimal and whose blind signatures are short. Our schemes are defined over bilinear groups and are proved secure in the common-reference-string model without random oracles and under standard assumptions: CDH and the decision-linear assumption. (We also give variants over asymmetric groups based on similar assumptions.) The blind signatures are Waters signatures, which consist of 2 group elements. Moreover, we instantiate partially blind signatures, where the message consists of a part hidden from the signer and a commonly known public part, and schemes achieving perfect blindness. We propose new variants of blind signatures, such as signer-friendly partially blind signatures, where the public part can be chosen by the signer without prior agreement, 3-party blind signatures, as well as blind signatures on multiple aggregated messages provided by independent sources. We also extend Waters signatures to non-binary alphabets by proving a new result on the underlying hash function.
AU - Blazy, Olivier
AU - Fuchsbauer, Georg
AU - Pointcheval, David
AU - Vergnaud, Damien
ID - 502
IS - 5
JF - Journal of Computer Security
TI - Short blind signatures
VL - 21
ER -
TY - JOUR
AB - Alkyd resins are polyesters containing unsaturated fatty acids that are used as binding agents in paints and coatings. Chemical drying of these polyesters is based on heavy metal catalyzed cross-linking of the unsaturated fatty acid moieties. Among the heavy-metal catalysts, cobalt complexes are the most effective, yet they have been proven to be carcinogenic. Therefore, strategies to replace the cobalt-based catalyst by environmentally friendlier and less toxic alternatives are under development. Here, we demonstrate for the first time that a laccase-mediator system can effectively replace the heavy-metal catalyst and cross-link alkyd resins. Interestingly, the biocatalytic reaction does not only work in aqueous media, but also in a solid film, where enzyme diffusion is limited. Within the catalytic cycle, the mediator oxidizes the alkyd resin and is regenerated by the laccase, which is uniformly distributed within the drying film as evidenced by confocal laser scanning microscopy. During gradual build-up of molecular weight, there is a concomitant decrease of the oxygen content in the film. A new optical sensor to follow oxygen consumption during the cross-linking reaction was developed and validated with state of the art techniques. A remarkable feature is the low sample amount required, which allows faster screening of new catalysts.
AU - Greimel, Katrin
AU - Perz, Veronika
AU - Koren, Klaus
AU - Feola, Roland
AU - Temel, Armin
AU - Sohar, Christian
AU - Herrero Acero, Enrique
AU - Klimant, Ingo
AU - Guebitz, Georg
ID - 505
IS - 2
JF - Green Chemistry
TI - Banning toxic heavy-metal catalysts from paints: Enzymatic cross-linking of alkyd resins
VL - 15
ER -
TY - JOUR
AB - Fertilization in flowering plants requires the temporal and spatial coordination of many developmental processes, including pollen production, anther dehiscence, ovule production, and pollen tube elongation. However, it remains elusive as to how this coordination occurs during reproduction. Here, we present evidence that endocytosis, involving heterotetrameric adaptor protein complex 2 (AP-2), plays a crucial role in fertilization. An Arabidopsis thaliana mutant ap2m displays multiple defects in pollen production and viability, as well as elongation of staminal filaments and pollen tubes, all of which are pivotal processes needed for fertilization. Of these abnormalities, the defects in elongation of staminal filaments and pollen tubes were partially rescued by exogenous auxin. Moreover, DR5rev:GFP (for green fluorescent protein) expression was greatly reduced in filaments and anthers in ap2m mutant plants. At the cellular level, ap2m mutants displayed defects in both endocytosis of N-(3-triethylammonium-propyl)-4- (4-diethylaminophenylhexatrienyl) pyridinium dibromide, a lypophilic dye used as an endocytosis marker, and polar localization of auxin-efflux carrier PIN FORMED2 (PIN2) in the stamen filaments. Moreover, these defects were phenocopied by treatment with Tyrphostin A23, an inhibitor of endocytosis. Based on these results, we propose that AP-2-dependent endocytosis plays a crucial role in coordinating the multiple developmental aspects of male reproductive organs by modulating cellular auxin level through the regulation of the amount and polarity of PINs.
AU - Kim, Soo
AU - Xu, Zheng
AU - Song, Kyungyoung
AU - Kim, Dae
AU - Kang, Hyangju
AU - Reichardt, Ilka
AU - Sohn, Eun
AU - Friml, Jirí
AU - Juergens, Gerd
AU - Hwang, Inhwan
ID - 507
IS - 8
JF - Plant Cell
TI - Adaptor protein complex 2-mediated endocytosis is crucial for male reproductive organ development in arabidopsis
VL - 25
ER -
TY - JOUR
AB - The phagocyte NADPH oxidase catalyzes the reduction of O2 to reactive oxygen species with microbicidal activity. It is composed of two membrane-spanning subunits, gp91-phox and p22-phox (encoded by CYBB and CYBA, respectively), and three cytoplasmic subunits, p40-phox, p47-phox, and p67-phox (encoded by NCF4, NCF1, and NCF2, respectively). Mutations in any of these genes can result in chronic granulomatous disease, a primary immunodeficiency characterized by recurrent infections. Using evolutionary mapping, we determined that episodes of adaptive natural selection have shaped the extracellular portion of gp91-phox during the evolution of mammals, which suggests that this region may have a function in host-pathogen interactions. On the basis of a resequencing analysis of approximately 35 kb of CYBB, CYBA, NCF2, and NCF4 in 102 ethnically diverse individuals (24 of African ancestry, 31 of European ancestry, 24 of Asian/Oceanians, and 23 US Hispanics), we show that the pattern of CYBA diversity is compatible with balancing natural selection, perhaps mediated by catalase-positive pathogens. NCF2 in Asian populations shows a pattern of diversity characterized by a differentiated haplotype structure. Our study provides insight into the role of pathogen-driven natural selection in an innate immune pathway and sheds light on the role of CYBA in endothelial, nonphagocytic NADPH oxidases, which are relevant in the pathogenesis of cardiovascular and other complex diseases.
AU - Tarazona Santos, Eduardo
AU - Machado, Moara
AU - Magalhães, Wagner
AU - Chen, Renee
AU - Lyon, Fernanda
AU - Burdett, Laurie
AU - Crenshaw, Andrew
AU - Fabbri, Cristina
AU - Pereira, Latife
AU - Pinto, Laelia
AU - Fernandes Redondo, Rodrigo A
AU - Sestanovich, Ben
AU - Yeager, Meredith
AU - Chanock, Stephen
ID - 508
IS - 9
JF - Molecular Biology and Evolution
TI - Evolutionary dynamics of the human NADPH oxidase genes CYBB, CYBA, NCF2, and NCF4: Functional implications
VL - 30
ER -
TY - JOUR
AB - Clathrin-mediated endocytosis (CME) regulates many aspects of plant development, including hormone signaling and responses to environmental stresses. Despite the importance of this process, the machinery that regulates CME in plants is largely unknown. In mammals, the heterotetrameric ADAPTOR PROTEIN COMPLEX-2 (AP-2) is required for the formation of clathrin-coated vesicles at the plasma membrane (PM). Although the existence of AP-2 has been predicted in Arabidopsis thaliana, the biochemistry and functionality of the complex is still uncharacterized. Here, we identified all the subunits of the Arabidopsis AP-2 by tandem affinity purification and found that one of the large AP-2 subunits, AP2A1, localized at the PM and interacted with clathrin. Furthermore, endocytosis of the leucine-rich repeat receptor kinase, BRASSINOSTEROID INSENSITIVE1 (BRI1), was shown to depend on AP-2. Knockdown of the two Arabidopsis AP2A genes or overexpression of a dominant-negative version of the medium AP-2 subunit, AP2M, impaired BRI1 endocytosis and enhanced the brassinosteroid signaling. Our data reveal that the CME machinery in Arabidopsis is evolutionarily conserved and that AP-2 functions in receptormediated endocytosis.
AU - Di Rubbo, Simone
AU - Irani, Niloufer
AU - Kim, Soo
AU - Xu, Zheng
AU - Gadeyne, Astrid
AU - Dejonghe, Wim
AU - Vanhoutte, Isabelle
AU - Persiau, Geert
AU - Eeckhout, Dominique
AU - Simon, Sibu
AU - Song, Kyungyoung
AU - Kleine Vehn, Jürgen
AU - Friml, Jirí
AU - De Jaeger, Geert
AU - Van Damme, Daniël
AU - Hwang, Inhwan
AU - Russinova, Eugenia
ID - 509
IS - 8
JF - Plant Cell
TI - The clathrin adaptor complex AP-2 mediates endocytosis of brassinosteroid INSENSITIVE1 in arabidopsis
VL - 25
ER -
TY - JOUR
AB - The native auxin, indole-3-acetic acid (IAA), is a major regulator of plant growth and development. Its nonuniform distribution between cells and tissues underlies the spatiotemporal coordination of many developmental events and responses to environmental stimuli. The regulation of auxin gradients and the formation of auxin maxima/minima most likely involve the regulation of both metabolic and transport processes. In this article, we have demonstrated that 2-oxindole-3-acetic acid (oxIAA) is a major primary IAA catabolite formed in Arabidopsis thaliana root tissues. OxIAA had little biological activity and was formed rapidly and irreversibly in response to increases in auxin levels. We further showed that there is cell type-specific regulation of oxIAA levels in the Arabidopsis root apex. We propose that oxIAA is an important element in the regulation of output from auxin gradients and, therefore, in the regulation of auxin homeostasis and response mechanisms.
AU - Pěnčík, Aleš
AU - Simonovik, Biljana
AU - Petersson, Sara
AU - Henyková, Eva
AU - Simon, Sibu
AU - Greenham, Kathleen
AU - Zhang, Yi
AU - Kowalczyk, Mariusz
AU - Estelle, Mark
AU - Zažímalová, Eva
AU - Novák, Ondřej
AU - Sandberg, Göran
AU - Ljung, Karin
ID - 511
IS - 10
JF - Plant Cell
TI - Regulation of auxin homeostasis and gradients in Arabidopsis roots through the formation of the indole-3-acetic acid catabolite 2-oxindole-3-acetic acid
VL - 25
ER -
TY - JOUR
AB - In plants, changes in local auxin concentrations can trigger a range of developmental processes as distinct tissues respond differently to the same auxin stimulus. However, little is known about how auxin is interpreted by individual cell types. We performed a transcriptomic analysis of responses to auxin within four distinct tissues of the Arabidopsis thaliana root and demonstrate that different cell types show competence for discrete responses. The majority of auxin‐responsive genes displayed a spatial bias in their induction or repression. The novel data set was used to examine how auxin influences tissue‐specific transcriptional regulation of cell‐identity markers. Additionally, the data were used in combination with spatial expression maps of the root to plot a transcriptomic auxin‐response gradient across the apical and basal meristem. The readout revealed a strong correlation for thousands of genes between the relative response to auxin and expression along the longitudinal axis of the root. This data set and comparative analysis provide a transcriptome‐level spatial breakdown of the response to auxin within an organ where this hormone mediates many aspects of development.
AU - Bargmann, Bastiaan
AU - Vanneste, Steffen
AU - Krouk, Gabriel
AU - Nawy, Tal
AU - Efroni, Idan
AU - Shani, Eilon
AU - Choe, Goh
AU - Friml, Jirí
AU - Bergmann, Dominique
AU - Estelle, Mark
AU - Birnbaum, Kenneth
ID - 516
IS - 1
JF - Molecular Systems Biology
TI - A map of cell type‐specific auxin responses
VL - 9
ER -
TY - JOUR
AB - Podoplanin, a mucin-like plasma membrane protein, is expressed by lymphatic endothelial cells and responsible for separation of blood and lymphatic circulation through activation of platelets. Here we show that podoplanin is also expressed by thymic fibroblastic reticular cells (tFRC), a novel thymic medulla stroma cell type associated with thymic conduits, and involved in development of natural regulatory T cells (nTreg). Young mice deficient in podoplanin lack nTreg owing to retardation of CD4+CD25+ thymocytes in the cortex and missing differentiation of Foxp3+ thymocytes in the medulla. This might be due to CCL21 that delocalizes upon deletion of the CCL21-binding podoplanin from medullar tFRC to cortex areas. The animals do not remain devoid of nTreg but generate them delayed within the first month resulting in Th2-biased hypergammaglobulinemia but not in the death-causing autoimmune phenotype of Foxp3-deficient Scurfy mice.
AU - Fuertbauer, Elke
AU - Zaujec, Jan
AU - Uhrin, Pavel
AU - Raab, Ingrid
AU - Weber, Michele
AU - Schachner, Helga
AU - Bauer, Miroslav
AU - Schütz, Gerhard
AU - Binder, Bernd
AU - Sixt, Michael K
AU - Kerjaschki, Dontscho
AU - Stockinger, Hannes
ID - 522
IS - 1-2
JF - Immunology Letters
TI - Thymic medullar conduits-associated podoplanin promotes natural regulatory T cells
VL - 154
ER -
TY - JOUR
AB - The apical-basal axis of the early plant embryo determines the body plan of the adult organism. To establish a polarized embryonic axis, plants evolved a unique mechanism that involves directional, cell-to-cell transport of the growth regulator auxin. Auxin transport relies on PIN auxin transporters [1], whose polar subcellular localization determines the flow directionality. PIN-mediated auxin transport mediates the spatial and temporal activity of the auxin response machinery [2-7] that contributes to embryo patterning processes, including establishment of the apical (shoot) and basal (root) embryo poles [8]. However, little is known of upstream mechanisms guiding the (re)polarization of auxin fluxes during embryogenesis [9]. Here, we developed a model of plant embryogenesis that correctly generates emergent cell polarities and auxin-mediated sequential initiation of apical-basal axis of plant embryo. The model relies on two precisely localized auxin sources and a feedback between auxin and the polar, subcellular PIN transporter localization. Simulations reproduced PIN polarity and auxin distribution, as well as previously unknown polarization events during early embryogenesis. The spectrum of validated model predictions suggests that our model corresponds to a minimal mechanistic framework for initiation and orientation of the apical-basal axis to guide both embryonic and postembryonic plant development.
AU - Wabnik, Krzysztof T
AU - Robert, Hélène
AU - Smith, Richard
AU - Friml, Jirí
ID - 527
IS - 24
JF - Current Biology
TI - Modeling framework for the establishment of the apical-basal embryonic axis in plants
VL - 23
ER -
TY - JOUR
AB - Establishment of the embryonic axis foreshadows the main body axis of adults both in plants and in animals, but underlying mechanisms are considered distinct. Plants utilize directional, cell-to-cell transport of the growth hormone auxin [1, 2] to generate an asymmetric auxin response that specifies the embryonic apical-basal axis [3-6]. The auxin flow directionality depends on the polarized subcellular localization of PIN-FORMED (PIN) auxin transporters [7, 8]. It remains unknown which mechanisms and spatial cues guide cell polarization and axis orientation in early embryos. Herein, we provide conceptually novel insights into the formation of embryonic axis in Arabidopsis by identifying a crucial role of localized tryptophan-dependent auxin biosynthesis [9-12]. Local auxin production at the base of young embryos and the accompanying PIN7-mediated auxin flow toward the proembryo are required for the apical auxin response maximum and the specification of apical embryonic structures. Later in embryogenesis, the precisely timed onset of localized apical auxin biosynthesis mediates PIN1 polarization, basal auxin response maximum, and specification of the root pole. Thus, the tight spatiotemporal control of distinct local auxin sources provides a necessary, non-cell-autonomous trigger for the coordinated cell polarization and subsequent apical-basal axis orientation during embryogenesis and, presumably, also for other polarization events during postembryonic plant life [13, 14].
AU - Robert, Hélène
AU - Grones, Peter
AU - Stepanova, Anna
AU - Robles, Linda
AU - Lokerse, Annemarie
AU - Alonso, Jose
AU - Weijers, Dolf
AU - Friml, Jirí
ID - 528
IS - 24
JF - Current Biology
TI - Local auxin sources orient the apical basal axis in arabidopsis embryos
VL - 23
ER -
TY - GEN
AB - In this work we present a flexible tool for tumor progression, which simulates the evolutionary dynamics of cancer. Tumor progression implements a multi-type branching process where the key parameters are the fitness landscape, the mutation rate, and the average time of cell division. The fitness of a cancer cell depends on the mutations it has accumulated. The input to our tool could be any fitness landscape, mutation rate, and cell division time, and the tool produces the growth dynamics and all relevant statistics.
AU - Reiter, Johannes
AU - Bozic, Ivana
AU - Chatterjee, Krishnendu
AU - Nowak, Martin
ID - 5399
SN - 2664-1690
TI - TTP: Tool for Tumor Progression
ER -
TY - GEN
AB - We consider partially observable Markov decision processes (POMDPs) with ω-regular conditions specified as parity objectives. The class of ω-regular languages extends regular languages to infinite strings and provides a robust specification language to express all properties used in verification, and parity objectives are canonical forms to express ω-regular conditions. The qualitative analysis problem given a POMDP and a parity objective asks whether there is a strategy to ensure that the objective is satis- fied with probability 1 (resp. positive probability). While the qualitative analysis problems are known to be undecidable even for very special cases of parity objectives, we establish decidability (with optimal complexity) of the qualitative analysis problems for POMDPs with all parity objectives under finite- memory strategies. We establish asymptotically optimal (exponential) memory bounds and EXPTIME- completeness of the qualitative analysis problems under finite-memory strategies for POMDPs with parity objectives.
AU - Chatterjee, Krishnendu
AU - Chmelik, Martin
AU - Tracol, Mathieu
ID - 5400
SN - 2664-1690
TI - What is decidable about partially observable Markov decision processes with ω-regular objectives
ER -
TY - GEN
AB - This document is created as a part of the project “Repository for Research Data at IST Austria”. It summarises the actual initiatives, projects and standards related to the project. It supports the preparation of standards and specifications for the project, which should be considered and followed to ensure interoperability and visibility of the uploaded data.
AU - Porsche, Jana
ID - 5401
TI - Initiatives and projects related to RD
ER -
TY - GEN
AB - Linearizability requires that the outcome of calls by competing threads to a concurrent data structure is the same as some sequential execution where each thread has exclusive access to the data structure. In an ordered data structure, such as a queue or a stack, linearizability is ensured by requiring threads commit in the order dictated by the sequential semantics of the data structure; e.g., in a concurrent queue implementation a dequeue can only remove the oldest element.
In this paper, we investigate the impact of this strict ordering, by comparing what linearizability allows to what existing implementations do. We first give an operational definition for linearizability which allows us to build the most general linearizable implementation as a transition system for any given sequential specification. We then use this operational definition to categorize linearizable implementations based on whether they are bound or free. In a bound implementation, whenever all threads observe the same logical state, the updates to the logical state and the temporal order of commits coincide. All existing queue implementations we know of are bound. We then proceed to present, to the best of our knowledge, the first ever free queue implementation. Our experiments show that free implementations have the potential for better performance by suffering less from contention.
AU - Henzinger, Thomas A
AU - Sezgin, Ali
ID - 5402
SN - 2664-1690
TI - How free is your linearizable concurrent data structure?
ER -
TY - GEN
AB - We consider concurrent games played by two-players on a finite state graph, where in every round the players simultaneously choose a move, and the current state along with the joint moves determine the successor state. We study the most fundamental objective for concurrent games, namely, mean-payoff or limit-average objective, where a reward is associated to every transition, and the goal of player 1 is to maximize the long-run average of the rewards, and the objective of player 2 is strictly the opposite (i.e., the games are zero-sum). The path constraint for player 1 could be qualitative, i.e., the mean-payoff is the maximal reward, or arbitrarily close to it; or quantitative, i.e., a given threshold between the minimal and maximal reward. We consider the computation of the almost-sure (resp. positive) winning sets, where player 1 can ensure that the path constraint is satisfied with probability 1 (resp. positive probability). Almost-sure winning with qualitative constraint exactly corresponds to the question whether there exists a strategy to ensure that the payoff is the maximal reward of the game. Our main results for qualitative path constraints are as follows: (1) we establish qualitative determinacy results that show for every state either player 1 has a strategy to ensure almost-sure (resp. positive) winning against all player-2 strategies or player 2 has a spoiling strategy to falsify almost-sure (resp. positive) winning against all player-1 strategies; (2) we present optimal strategy complexity results that precisely characterize the classes of strategies required for almost-sure and positive winning for both players; and (3) we present quadratic time algorithms to compute the almost-sure and the positive winning sets, matching the best known bound of the algorithms for much simpler problems (such as reachability objectives). For quantitative constraints we show that a polynomial time solution for the almost-sure or the positive winning set would imply a solution to a long-standing open problem (of solving the value problem of mean-payoff games) that is not known to be in polynomial time.
AU - Chatterjee, Krishnendu
AU - Ibsen-Jensen, Rasmus
ID - 5403
SN - 2664-1690
TI - Qualitative analysis of concurrent mean-payoff games
ER -
TY - GEN
AB - We study finite-state two-player (zero-sum) concurrent mean-payoff games played on a graph. We focus on the important sub-class of ergodic games where all states are visited infinitely often with probability 1. The algorithmic study of ergodic games was initiated in a seminal work of Hoffman and Karp in 1966, but all basic complexity questions have remained unresolved. Our main results for ergodic games are as follows: We establish (1) an optimal exponential bound on the patience of stationary strategies (where patience of a distribution is the inverse of the smallest positive probability and represents a complexity measure of a stationary strategy); (2) the approximation problem lie in FNP; (3) the approximation problem is at least as hard as the decision problem for simple stochastic games (for which NP and coNP is the long-standing best known bound). We show that the exact value can be expressed in the existential theory of the reals, and also establish square-root sum hardness for a related class of games.
AU - Chatterjee, Krishnendu
AU - Ibsen-Jensen, Rasmus
ID - 5404
SN - 2664-1690
TI - The complexity of ergodic games
ER -
TY - GEN
AB - The theory of graph games is the foundation for modeling and synthesizing reactive processes. In the synthesis of stochastic processes, we use 2-1/2-player games where some transitions of the game graph are controlled by two adversarial players, the System and the Environment, and the other transitions are determined probabilistically. We consider 2-1/2-player games where the objective of the System is the conjunction of a qualitative objective (specified as a parity condition) and a quantitative objective (specified as a mean-payoff condition). We establish that the problem of deciding whether the System can ensure that the probability to satisfy the mean-payoff parity objective is at least a given threshold is in NP ∩ coNP, matching the best known bound in the special case of 2-player games (where all transitions are deterministic) with only parity objectives, or with only mean-payoff objectives. We present an algorithm running
in time O(d · n^{2d}·MeanGame) to compute the set of almost-sure winning states from which the objective
can be ensured with probability 1, where n is the number of states of the game, d the number of priorities
of the parity objective, and MeanGame is the complexity to compute the set of almost-sure winning states
in 2-1/2-player mean-payoff games. Our results are useful in the synthesis of stochastic reactive systems
with both functional requirement (given as a qualitative objective) and performance requirement (given
as a quantitative objective).
AU - Chatterjee, Krishnendu
AU - Doyen, Laurent
AU - Gimbert, Hugo
AU - Oualhadj, Youssouf
ID - 5405
SN - 2664-1690
TI - Perfect-information stochastic mean-payoff parity games
ER -
TY - GEN
AB - We consider the distributed synthesis problem fortemporal logic specifications. Traditionally, the problem has been studied for LTL, and the previous results show that the problem is decidable iff there is no information fork in the architecture. We consider the problem for fragments of LTLand our main results are as follows: (1) We show that the problem is undecidable for architectures with information forks even for the fragment of LTL with temporal operators restricted to next and eventually. (2) For specifications restricted to globally along with non-nested next operators, we establish decidability (in EXPSPACE) for star architectures where the processes receive disjoint inputs, whereas we establish undecidability for architectures containing an information fork-meet structure. (3)Finally, we consider LTL without the next operator, and establish decidability (NEXPTIME-complete) for all architectures for a fragment that consists of a set of safety assumptions, and a set of guarantees where each guarantee is a safety, reachability, or liveness condition.
AU - Chatterjee, Krishnendu
AU - Henzinger, Thomas A
AU - Otop, Jan
AU - Pavlogiannis, Andreas
ID - 5406
SN - 2664-1690
TI - Distributed synthesis for LTL Fragments
ER -
TY - GEN
AB - This document is created as a part of the project “Repository for Research Data at IST Austria”. It summarises the mandatory features, which need to be fulfilled to provide an institutional repository as a platform and also a service to the scientists at the institute. It also includes optional features, which would be of strong benefit for the scientists and would increase the usage of the repository, and hence the visibility of research at IST Austria.
AU - Porsche, Jana
ID - 5407
TI - Technical requirements and features
ER -
TY - GEN
AB - We consider two-player partial-observation stochastic games where player 1 has partial observation and player 2 has perfect observation. The winning condition we study are omega-regular conditions specified as parity objectives. The qualitative analysis problem given a partial-observation stochastic game and a parity objective asks whether there is a strategy to ensure that the objective is satisfied with probability 1 (resp. positive probability). While the qualitative analysis problems are known to be undecidable even for very special cases of parity objectives, they were shown to be decidable in 2EXPTIME under finite-memory strategies. We improve the complexity and show that the qualitative analysis problems for partial-observation stochastic parity games under finite-memory strategies are
EXPTIME-complete; and also establish optimal (exponential) memory bounds for finite-memory strategies required for qualitative analysis.
AU - Chatterjee, Krishnendu
AU - Doyen, Laurent
AU - Nain, Sumit
AU - Vardi, Moshe
ID - 5408
SN - 2664-1690
TI - The complexity of partial-observation stochastic parity games with finite-memory strategies
ER -
TY - GEN
AB - The edit distance between two (untimed) traces is the minimum cost of a sequence of edit operations (insertion, deletion, or substitution) needed to transform one trace to the other. Edit distances have been extensively studied in the untimed setting, and form the basis for approximate matching of sequences in different domains such as coding theory, parsing, and speech recognition.
In this paper, we lift the study of edit distances from untimed languages to the timed setting. We define an edit distance between timed words which incorporates both the edit distance between the untimed words and the absolute difference in timestamps. Our edit distance between two timed words is computable in polynomial time. Further, we show that the edit distance between a timed word and a timed language generated by a timed automaton, defined as the edit distance between the word and the closest word in the language, is PSPACE-complete. While computing the edit distance between two timed automata is undecidable, we show that the approximate version, where we decide if the edit distance between two timed automata is either less than a given parameter or more than delta away from the parameter, for delta>0, can be solved in exponential space and is EXPSPACE-hard. Our definitions and techniques can be generalized to the setting of hybrid systems, and we show analogous decidability results for rectangular automata.
AU - Chatterjee, Krishnendu
AU - Ibsen-Jensen, Rasmus
AU - Majumdar, Rupak
ID - 5409
SN - 2664-1690
TI - Edit distance for timed automata
ER -
TY - GEN
AB - Board games, like Tic-Tac-Toe and CONNECT-4, play an important role not only in development of mathematical and logical skills, but also in emotional and social development. In this paper, we address the problem of generating targeted starting positions for such games. This can facilitate new approaches for bringing novice players to mastery, and also leads to discovery of interesting game variants.
Our approach generates starting states of varying hardness levels for player 1 in a two-player board game, given rules of the board game, the desired number of steps required for player 1 to win, and the expertise levels of the two players. Our approach leverages symbolic methods and iterative simulation to efficiently search the extremely large state space. We present experimental results that include discovery of states of varying hardness levels for several simple grid-based board games. Also, the presence of such states for standard game variants like Tic-Tac-Toe on board size 4x4 opens up new games to be played that have not been played for ages since the default start state is heavily biased.
AU - Ahmed, Umair
AU - Chatterjee, Krishnendu
AU - Gulwani, Sumit
ID - 5410
SN - 2664-1690
TI - Automatic generation of alternative starting positions for traditional board games
ER -
TY - CHAP
AU - Dragoi, Cezara
AU - Gupta, Ashutosh
AU - Henzinger, Thomas A
ID - 5747
SN - 0302-9743
T2 - Computer Aided Verification
TI - Automatic Linearizability Proofs of Concurrent Objects with Cooperating Updates
VL - 8044
ER -
TY - JOUR
AB - Due to their sessile lifestyles, plants need to deal with the limitations and stresses imposed by the changing environment. Plants cope with these by a remarkable developmental flexibility, which is embedded in their strategy to survive. Plants can adjust their size, shape and number of organs, bend according to gravity and light, and regenerate tissues that were damaged, utilizing a coordinating, intercellular signal, the plant hormone, auxin. Another versatile signal is the cation, Ca2+, which is a crucial second messenger for many rapid cellular processes during responses to a wide range of endogenous and environmental signals, such as hormones, light, drought stress and others. Auxin is a good candidate for one of these Ca2+-activating signals. However, the role of auxin-induced Ca2+ signaling is poorly understood. Here, we will provide an overview of possible developmental and physiological roles, as well as mechanisms underlying the interconnection of Ca2+ and auxin signaling.
AU - Vanneste, Steffen
AU - Friml, Jiří
ID - 10895
IS - 4
JF - Plants
KW - Plant Science
KW - Ecology
KW - Ecology
KW - Evolution
KW - Behavior and Systematics
SN - 2223-7747
TI - Calcium: The missing link in auxin action
VL - 2
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 - We study two-player zero-sum games over infinite-state graphs equipped with ωB and finitary conditions. Our first contribution is about the strategy complexity, i.e the memory required for winning strategies: we prove that over general infinite-state graphs, memoryless strategies are sufficient for finitary Büchi, and finite-memory suffices for finitary parity games. We then study pushdown games with boundedness conditions, with two contributions. First we prove a collapse result for pushdown games with ωB-conditions, implying the decidability of solving these games. Second we consider pushdown games with finitary parity along with stack boundedness conditions, and show that solving these games is EXPTIME-complete.
AU - Chatterjee, Krishnendu
AU - Fijalkow, Nathanaël
ID - 1374
T2 - 22nd EACSL Annual Conference on Computer Science Logic
TI - Infinite-state games with finitary conditions
VL - 23
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 - CONF
AB - It is often difficult to correctly implement a Boolean controller for a complex system, especially when concurrency is involved. Yet, it may be easy to formally specify a controller. For instance, for a pipelined processor it suffices to state that the visible behavior of the pipelined system should be identical to a non-pipelined reference system (Burch-Dill paradigm). We present a novel procedure to efficiently synthesize multiple Boolean control signals from a specification given as a quantified first-order formula (with a specific quantifier structure). Our approach uses uninterpreted functions to abstract details of the design. We construct an unsatisfiable SMT formula from the given specification. Then, from just one proof of unsatisfiability, we use a variant of Craig interpolation to compute multiple coordinated interpolants that implement the Boolean control signals. Our method avoids iterative learning and back-substitution of the control functions. We applied our approach to synthesize a controller for a simple two-stage pipelined processor, and present first experimental results.
AU - Hofferek, Georg
AU - Gupta, Ashutosh
AU - Könighofer, Bettina
AU - Jiang, Jie
AU - Bloem, Roderick
ID - 1385
T2 - 2013 Formal Methods in Computer-Aided Design
TI - Synthesizing multiple boolean functions using interpolation on a single proof
ER -
TY - CONF
AB - Choices made by nondeterministic word automata depend on both the past (the prefix of the word read so far) and the future (the suffix yet to be read). In several applications, most notably synthesis, the future is diverse or unknown, leading to algorithms that are based on deterministic automata. Hoping to retain some of the advantages of nondeterministic automata, researchers have studied restricted classes of nondeterministic automata. Three such classes are nondeterministic automata that are good for trees (GFT; i.e., ones that can be expanded to tree automata accepting the derived tree languages, thus whose choices should satisfy diverse futures), good for games (GFG; i.e., ones whose choices depend only on the past), and determinizable by pruning (DBP; i.e., ones that embody equivalent deterministic automata). The theoretical properties and relative merits of the different classes are still open, having vagueness on whether they really differ from deterministic automata. In particular, while DBP ⊆ GFG ⊆ GFT, it is not known whether every GFT automaton is GFG and whether every GFG automaton is DBP. Also open is the possible succinctness of GFG and GFT automata compared to deterministic automata. We study these problems for ω-regular automata with all common acceptance conditions. We show that GFT=GFG⊃DBP, and describe a determinization construction for GFG automata.
AU - Boker, Udi
AU - Kuperberg, Denis
AU - Kupferman, Orna
AU - Skrzypczak, Michał
ID - 1387
IS - PART 2
TI - Nondeterminism in the presence of a diverse or unknown future
VL - 7966
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 - THES
AB - Epithelial spreading is a critical part of various developmental and wound repair processes. Here we use zebrafish epiboly as a model system to study the cellular and molecular mechanisms underlying the spreading of epithelial sheets. During zebrafish epiboly the enveloping cell layer (EVL), a simple squamous epithelium, spreads over the embryo to eventually cover the entire yolk cell by the end of gastrulation. The EVL leading edge is anchored through tight junctions to the yolk syncytial layer (YSL), where directly adjacent to the EVL margin a contractile actomyosin ring is formed that is thought to drive EVL epiboly. The prevalent view in the field was that the contractile ring exerts a pulling force on the EVL margin, which pulls the EVL towards the vegetal pole. However, how this force is generated and how it affects EVL morphology still remains elusive. Moreover, the cellular mechanisms mediating the increase in EVL surface area, while maintaining tissue integrity and function are still unclear. Here we show that the YSL actomyosin ring pulls on the EVL margin by two distinct force-generating mechanisms. One mechanism is based on contraction of the ring around its circumference, as previously proposed. The second mechanism is based on actomyosin retrogade flows, generating force through resistance against the substrate. The latter can function at any epiboly stage even in situations where the contraction-based mechanism is unproductive. Additionally, we demonstrate that during epiboly the EVL is subjected to anisotropic tension, which guides the orientation of EVL cell division along the main axis (animal-vegetal) of tension. The influence of tension in cell division orientation involves cell elongation and requires myosin-2 activity for proper spindle alignment. Strikingly, we reveal that tension-oriented cell divisions release anisotropic tension within the EVL and that in the absence of such divisions, EVL cells undergo ectopic fusions. We conclude that forces applied to the EVL by the action of the YSL actomyosin ring generate a tension anisotropy in the EVL that orients cell divisions, which in turn limit tissue tension increase thereby facilitating tissue spreading.
AU - Campinho, Pedro
ID - 1406
TI - Mechanics of zebrafish epiboly: Tension-oriented cell divisions limit anisotropic tissue tension in epithelial spreading
ER -
TY - JOUR
AB - Stimfit is a free cross-platform software package for viewing and analyzing electrophysiological data. It supports most standard file types for cellular neurophysiology and other biomedical formats. Its analysis algorithms have been used and validated in several experimental laboratories. Its embedded Python scripting interface makes Stimfit highly extensible and customizable.
AU - Schlögl, Alois
AU - Jonas, Peter M
AU - Schmidt-Hieber, C.
AU - Guzman, S. J.
ID - 10396
IS - SI-1-Track-G
JF - Biomedical Engineering / Biomedizinische Technik
KW - biomedical engineering
KW - data analysis
KW - free software
SN - 0013-5585
TI - Stimfit: A fast visualization and analysis environment for cellular neurophysiology
VL - 58
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 - JOUR
AB - Traditional statistical methods for confidentiality protection of statistical databases do not scale well to deal with GWAS databases especially in terms of guarantees regarding protection from linkage to external information. The more recent concept of differential privacy, introduced by the cryptographic community, is an approach which provides a rigorous definition of privacy with meaningful privacy guarantees in the presence of arbitrary external information, although the guarantees may come at a serious price in terms of data utility. Building on such notions, we propose new methods to release aggregate GWAS data without compromising an individual’s privacy. We present methods for releasing differentially private minor allele frequencies, chi-square statistics and p-values. We compare these approaches on simulated data and on a GWAS study of canine hair length involving 685 dogs. We also propose a privacy-preserving method for finding genome-wide associations based on a differentially-private approach to penalized logistic regression.
AU - Uhler, Caroline
AU - Slavkovic, Aleksandra
AU - Fienberg, Stephen
ID - 2009
IS - 1
JF - Journal of Privacy and Confidentiality
TI - Privacy-preserving data sharing for genome-wide association studies
VL - 5
ER -
TY - JOUR
AB - Many algorithms for inferring causality rely heavily on the faithfulness assumption. The main justification for imposing this assumption is that the set of unfaithful distributions has Lebesgue measure zero, since it can be seen as a collection of hypersurfaces in a hypercube. However, due to sampling error the faithfulness condition alone is not sufficient for statistical estimation, and strong-faithfulness has been proposed and assumed to achieve uniform or high-dimensional consistency. In contrast to the plain faithfulness assumption, the set of distributions that is not strong-faithful has nonzero Lebesgue measure and in fact, can be surprisingly large as we show in this paper. We study the strong-faithfulness condition from a geometric and combinatorial point of view and give upper and lower bounds on the Lebesgue measure of strong-faithful distributions for various classes of directed acyclic graphs. Our results imply fundamental limitations for the PC-algorithm and potentially also for other algorithms based on partial correlation testing in the Gaussian case.
AU - Uhler, Caroline
AU - Raskutti, Garvesh
AU - Bühlmann, Peter
AU - Yu, Bin
ID - 2010
IS - 2
JF - The Annals of Statistics
TI - Geometry of the faithfulness assumption in causal inference
VL - 41
ER -
TY - CONF
AB - There is a trade-off between performance and correctness in implementing concurrent data structures. Better performance may be achieved at the expense of relaxing correctness, by redefining the semantics of data structures. We address such a redefinition of data structure semantics and present a systematic and formal framework for obtaining new data structures by quantitatively relaxing existing ones. We view a data structure as a sequential specification S containing all "legal" sequences over an alphabet of method calls. Relaxing the data structure corresponds to defining a distance from any sequence over the alphabet to the sequential specification: the k-relaxed sequential specification contains all sequences over the alphabet within distance k from the original specification. In contrast to other existing work, our relaxations are semantic (distance in terms of data structure states). As an instantiation of our framework, we present two simple yet generic relaxation schemes, called out-of-order and stuttering relaxation, along with several ways of computing distances. We show that the out-of-order relaxation, when further instantiated to stacks, queues, and priority queues, amounts to tolerating bounded out-of-order behavior, which cannot be captured by a purely syntactic relaxation (distance in terms of sequence manipulation, e.g. edit distance). We give concurrent implementations of relaxed data structures and demonstrate that bounded relaxations provide the means for trading correctness for performance in a controlled way. The relaxations are monotonic which further highlights the trade-off: increasing k increases the number of permitted sequences, which as we demonstrate can lead to better performance. Finally, since a relaxed stack or queue also implements a pool, we actually have new concurrent pool implementations that outperform the state-of-the-art ones.
AU - Henzinger, Thomas A
AU - Kirsch, Christoph
AU - Payer, Hannes
AU - Sezgin, Ali
AU - Sokolova, Ana
ID - 2181
SN - 978-1-4503-1832-7
T2 - Proceedings of the 40th annual ACM SIGPLAN-SIGACT symposium on Principles of programming language
TI - Quantitative relaxation of concurrent data structures
ER -
TY - CONF
AB - We propose a general framework for abstraction with respect to quantitative properties, such as worst-case execution time, or power consumption. Our framework provides a systematic way for counter-example guided abstraction refinement for quantitative properties. The salient aspect of the framework is that it allows anytime verification, that is, verification algorithms that can be stopped at any time (for example, due to exhaustion of memory), and report approximations that improve monotonically when the algorithms are given more time. We instantiate the framework with a number of quantitative abstractions and refinement schemes, which differ in terms of how much quantitative information they keep from the original system. We introduce both state-based and trace-based quantitative abstractions, and we describe conditions that define classes of quantitative properties for which the abstractions provide over-approximations. We give algorithms for evaluating the quantitative properties on the abstract systems. We present algorithms for counter-example based refinements for quantitative properties for both state-based and segment-based abstractions. We perform a case study on worst-case execution time of executables to evaluate the anytime verification aspect and the quantitative abstractions we proposed.
AU - Cerny, Pavol
AU - Henzinger, Thomas A
AU - Radhakrishna, Arjun
ID - 2182
T2 - Proceedings of the 40th annual ACM SIGPLAN-SIGACT symposium on Principles of programming language
TI - Quantitative abstraction refinement
ER -
TY - CONF
AB - A straight skeleton is a well-known geometric structure, and several algorithms exist to construct the straight skeleton for a given polygon or planar straight-line graph. In this paper, we ask the reverse question: Given the straight skeleton (in form of a planar straight-line graph, with some rays to infinity), can we reconstruct a planar straight-line graph for which this was the straight skeleton? We show how to reduce this problem to the problem of finding a line that intersects a set of convex polygons. We can find these convex polygons and all such lines in $O(nlog n)$ time in the Real RAM computer model, where $n$ denotes the number of edges of the input graph. We also explain how our approach can be used for recognizing Voronoi diagrams of points, thereby completing a partial solution provided by Ash and Bolker in 1985.
AU - Biedl, Therese
AU - Held, Martin
AU - Huber, Stefan
ID - 2209
TI - Recognizing straight skeletons and Voronoi diagrams and reconstructing their input
ER -
TY - CONF
AB - A straight skeleton is a well-known geometric structure, and several algorithms exist to construct the straight skeleton for a given polygon. In this paper, we ask the reverse question: Given the straight skeleton (in form of a tree with a drawing in the plane, but with the exact position of the leaves unspecified), can we reconstruct the polygon? We show that in most cases there exists at most one polygon; in the remaining case there is an infinite number of polygons determined by one angle that can range in an interval. We can find this (set of) polygon(s) in linear time in the Real RAM computer model.
AU - Biedl, Therese
AU - Held, Martin
AU - Huber, Stefan
ID - 2210
T2 - 29th European Workshop on Computational Geometry
TI - Reconstructing polygons from embedded straight skeletons
ER -
TY - CONF
AB - We describe new extensions of the Vampire theorem prover for computing tree interpolants. These extensions generalize Craig interpolation in Vampire, and can also be used to derive sequence interpolants. We evaluated our implementation on a large number of examples over the theory of linear integer arithmetic and integer-indexed arrays, with and without quantifiers. When compared to other methods, our experiments show that some examples could only be solved by our implementation.
AU - Blanc, Régis
AU - Gupta, Ashutosh
AU - Kovács, Laura
AU - Kragl, Bernhard
ID - 2237
TI - Tree interpolation in Vampire
VL - 8312
ER -
TY - CONF
AB - We study the problem of achieving a given value in Markov decision processes (MDPs) with several independent discounted reward objectives. We consider a generalised version of discounted reward objectives, in which the amount of discounting depends on the states visited and on the objective. This definition extends the usual definition of discounted reward, and allows to capture the systems in which the value of different commodities diminish at different and variable rates.
We establish results for two prominent subclasses of the problem, namely state-discount models where the discount factors are only dependent on the state of the MDP (and independent of the objective), and reward-discount models where they are only dependent on the objective (but not on the state of the MDP). For the state-discount models we use a straightforward reduction to expected total reward and show that the problem whether a value is achievable can be solved in polynomial time. For the reward-discount model we show that memory and randomisation of the strategies are required, but nevertheless that the problem is decidable and it is sufficient to consider strategies which after a certain number of steps behave in a memoryless way.
For the general case, we show that when restricted to graphs (i.e. MDPs with no randomisation), pure strategies and discount factors of the form 1/n where n is an integer, the problem is in PSPACE and finite memory suffices for achieving a given value. We also show that when the discount factors are not of the form 1/n, the memory required by a strategy can be infinite.
AU - Chatterjee, Krishnendu
AU - Forejt, Vojtěch
AU - Wojtczak, Dominik
ID - 2238
TI - Multi-objective discounted reward verification in graphs and MDPs
VL - 8312
ER -
TY - CONF
AB - We show that modal logic over universally first-order definable classes of transitive frames is decidable. More precisely, let K be an arbitrary class of transitive Kripke frames definable by a universal first-order sentence. We show that the global and finite global satisfiability problems of modal logic over K are decidable in NP, regardless of choice of K. We also show that the local satisfiability and the finite local satisfiability problems of modal logic over K are decidable in NEXPTIME.
AU - Michaliszyn, Jakub
AU - Otop, Jan
ID - 2243
TI - Elementary modal logics over transitive structures
VL - 23
ER -
TY - CONF
AB - We consider two systems (α1,...,αm) and (β1,...,βn) of curves drawn on a compact two-dimensional surface ℳ with boundary. Each αi and each βj is either an arc meeting the boundary of ℳ at its two endpoints, or a closed curve. The αi are pairwise disjoint except for possibly sharing endpoints, and similarly for the βj. We want to "untangle" the βj from the αi by a self-homeomorphism of ℳ; more precisely, we seek an homeomorphism φ: ℳ → ℳ fixing the boundary of ℳ pointwise such that the total number of crossings of the αi with the φ(βj) is as small as possible. This problem is motivated by an application in the algorithmic theory of embeddings and 3-manifolds. We prove that if ℳ is planar, i.e., a sphere with h ≥ 0 boundary components ("holes"), then O(mn) crossings can be achieved (independently of h), which is asymptotically tight, as an easy lower bound shows. In general, for an arbitrary (orientable or nonorientable) surface ℳ with h holes and of (orientable or nonorientable) genus g ≥ 0, we obtain an O((m + n)4) upper bound, again independent of h and g.
AU - Matoušek, Jiří
AU - Sedgwick, Eric
AU - Tancer, Martin
AU - Wagner, Uli
ID - 2244
TI - Untangling two systems of noncrossing curves
VL - 8242
ER -
TY - JOUR
AB - Cooperative behavior, where one individual incurs a cost to help another, is a wide spread phenomenon. Here we study direct reciprocity in the context of the alternating Prisoner's Dilemma. We consider all strategies that can be implemented by one and two-state automata. We calculate the payoff matrix of all pairwise encounters in the presence of noise. We explore deterministic selection dynamics with and without mutation. Using different error rates and payoff values, we observe convergence to a small number of distinct equilibria. Two of them are uncooperative strict Nash equilibria representing always-defect (ALLD) and Grim. The third equilibrium is mixed and represents a cooperative alliance of several strategies, dominated by a strategy which we call Forgiver. Forgiver cooperates whenever the opponent has cooperated; it defects once when the opponent has defected, but subsequently Forgiver attempts to re-establish cooperation even if the opponent has defected again. Forgiver is not an evolutionarily stable strategy, but the alliance, which it rules, is asymptotically stable. For a wide range of parameter values the most commonly observed outcome is convergence to the mixed equilibrium, dominated by Forgiver. Our results show that although forgiving might incur a short-term loss it can lead to a long-term gain. Forgiveness facilitates stable cooperation in the presence of exploitation and noise.
AU - Zagorsky, Benjamin
AU - Reiter, Johannes
AU - Chatterjee, Krishnendu
AU - Nowak, Martin
ID - 2247
IS - 12
JF - PLoS One
TI - Forgiver triumphs in alternating prisoner's dilemma
VL - 8
ER -
TY - JOUR
AB - Linked (Open) Data - bibliographic data on the Semantic Web. Report of the Working Group on Linked Data to the plenary assembly of the Austrian Library Network (translation of the title). Linked Data stands for a certain approach to publishing data on the Web. The underlying idea is to harmonise heterogeneous data sources of different origin in order to improve their accessibility and interoperability, effectively making them queryable as a big distributed database. This report summarises relevant developments in Europe as well as the Linked Data Working Group‘s strategic and technical considerations regarding the publishing of the Austrian Library Network’s (OBV’s) bibliographic datasets. It concludes with the mutual agreement that the implementation of Linked Data principles within the OBV can only be taken into consideration accompanied by a discussion about the provision of the datasets under a free license.
AU - Danowski, Patrick
AU - Goldfarb, Doron
AU - Schaffner, Verena
AU - Seidler, Wolfram
ID - 2256
IS - 3/4
JF - VÖB Mitteilungen
TI - Linked (Open) Data - Bibliographische Daten im Semantic Web
VL - 66
ER -
TY - CONF
AB - In a digital signature scheme with message recovery, rather than transmitting the message m and its signature σ, a single enhanced signature τ is transmitted. The verifier is able to recover m from τ and at the same time verify its authenticity. The two most important parameters of such a scheme are its security and overhead |τ| − |m|. A simple argument shows that for any scheme with “n bits security” |τ| − |m| ≥ n, i.e., the overhead is lower bounded by the security parameter n. Currently, the best known constructions in the random oracle model are far from this lower bound requiring an overhead of n + logq h , where q h is the number of queries to the random oracle. In this paper we give a construction which basically matches the n bit lower bound. We propose a simple digital signature scheme with n + o(logq h ) bits overhead, where q h denotes the number of random oracle queries.
Our construction works in two steps. First, we propose a signature scheme with message recovery having optimal overhead in a new ideal model, the random invertible function model. Second, we show that a four-round Feistel network with random oracles as round functions is tightly “public-indifferentiable” from a random invertible function. At the core of our indifferentiability proof is an almost tight upper bound for the expected number of edges of the densest “small” subgraph of a random Cayley graph, which may be of independent interest.
AU - Kiltz, Eike
AU - Pietrzak, Krzysztof Z
AU - Szegedy, Mario
ID - 2258
TI - Digital signatures with minimal overhead from indifferentiable random invertible functions
VL - 8042
ER -
TY - CONF
AB - The learning with rounding (LWR) problem, introduced by Banerjee, Peikert and Rosen at EUROCRYPT ’12, is a variant of learning with errors (LWE), where one replaces random errors with deterministic rounding. The LWR problem was shown to be as hard as LWE for a setting of parameters where the modulus and modulus-to-error ratio are super-polynomial. In this work we resolve the main open problem and give a new reduction that works for a larger range of parameters, allowing for a polynomial modulus and modulus-to-error ratio. In particular, a smaller modulus gives us greater efficiency, and a smaller modulus-to-error ratio gives us greater security, which now follows from the worst-case hardness of GapSVP with polynomial (rather than super-polynomial) approximation factors.
As a tool in the reduction, we show that there is a “lossy mode” for the LWR problem, in which LWR samples only reveal partial information about the secret. This property gives us several interesting new applications, including a proof that LWR remains secure with weakly random secrets of sufficient min-entropy, and very simple constructions of deterministic encryption, lossy trapdoor functions and reusable extractors.
Our approach is inspired by a technique of Goldwasser et al. from ICS ’10, which implicitly showed the existence of a “lossy mode” for LWE. By refining this technique, we also improve on the parameters of that work to only requiring a polynomial (instead of super-polynomial) modulus and modulus-to-error ratio.
AU - Alwen, Joel F
AU - Krenn, Stephan
AU - Pietrzak, Krzysztof Z
AU - Wichs, Daniel
ID - 2259
IS - 1
TI - Learning with rounding, revisited: New reduction properties and applications
VL - 8042
ER -
TY - CONF
AB - Direct Anonymous Attestation (DAA) is one of the most complex cryptographic protocols deployed in practice. It allows an embedded secure processor known as a Trusted Platform Module (TPM) to attest to the configuration of its host computer without violating the owner’s privacy. DAA has been standardized by the Trusted Computing Group and ISO/IEC.
The security of the DAA standard and all existing schemes is analyzed in the random-oracle model. We provide the first constructions of DAA in the standard model, that is, without relying on random oracles. Our constructions use new building blocks, including the first efficient signatures of knowledge in the standard model, which have many applications beyond DAA.
AU - Bernhard, David
AU - Fuchsbauer, Georg
AU - Ghadafi, Essam
ID - 2260
TI - Efficient signatures of knowledge and DAA in the standard model
VL - 7954
ER -
TY - JOUR
AB - Faithful progression through the cell cycle is crucial to the maintenance and developmental potential of stem cells. Here, we demonstrate that neural stem cells (NSCs) and intermediate neural progenitor cells (NPCs) employ a zinc-finger transcription factor specificity protein 2 (Sp2) as a cell cycle regulator in two temporally and spatially distinct progenitor domains. Differential conditional deletion of Sp2 in early embryonic cerebral cortical progenitors, and perinatal olfactory bulb progenitors disrupted transitions through G1, G2 and M phases, whereas DNA synthesis appeared intact. Cell-autonomous function of Sp2 was identified by deletion of Sp2 using mosaic analysis with double markers, which clearly established that conditional Sp2-null NSCs and NPCs are M phase arrested in vivo. Importantly, conditional deletion of Sp2 led to a decline in the generation of NPCs and neurons in the developing and postnatal brains. Our findings implicate Sp2-dependent mechanisms as novel regulators of cell cycle progression, the absence of which disrupts neurogenesis in the embryonic and postnatal brain.
AU - Liang, Huixuan
AU - Xiao, Guanxi
AU - Yin, Haifeng
AU - Hippenmeyer, Simon
AU - Horowitz, Jonathan
AU - Ghashghaei, Troy
ID - 2264
IS - 3
JF - Development
TI - Neural development is dependent on the function of specificity protein 2 in cell cycle progression
VL - 140
ER -
TY - CONF
AB - Representation languages for coalitional games are a key research area in algorithmic game theory. There is an inher-
ent tradeoff between how general a language is, allowing it to capture more elaborate games, and how hard it is computationally to optimize and solve such games. One prominent such language is the simple yet expressive
Weighted Graph Games (WGGs) representation (Deng and Papadimitriou 1994), which maintains knowledge about synergies between agents in the form of an edge weighted graph. We consider the problem of finding the optimal coalition structure in WGGs. The agents in such games are vertices in a graph, and the value of a coalition is the sum of the weights of the edges present between coalition members. The optimal coalition structure is a partition of the agents to coalitions, that maximizes the sum of utilities obtained by the coalitions. We show that finding the optimal coalition structure is not only hard for general graphs, but is also intractable for restricted families such as planar graphs which are amenable for many other combinatorial problems. We then provide algorithms with constant factor approximations for planar, minorfree and bounded degree graphs.
AU - Bachrach, Yoram
AU - Kohli, Pushmeet
AU - Kolmogorov, Vladimir
AU - Zadimoghaddam, Morteza
ID - 2270
TI - Optimal Coalition Structures in Cooperative Graph Games
ER -
TY - CONF
AB - We consider Conditional Random Fields (CRFs) with pattern-based potentials defined on a chain. In this model the energy of a string (labeling) x1...xn is the sum of terms over intervals [i,j] where each term is non-zero only if the substring xi...xj equals a prespecified pattern α. Such CRFs can be naturally applied to many sequence tagging problems.
We present efficient algorithms for the three standard inference tasks in a CRF, namely computing (i) the partition function, (ii) marginals, and (iii) computing the MAP. Their complexities are respectively O(nL), O(nLℓmax) and O(nLmin{|D|,log(ℓmax+1)}) where L is the combined length of input patterns, ℓmax is the maximum length of a pattern, and D is the input alphabet. This improves on the previous algorithms of (Ye et al., 2009) whose complexities are respectively O(nL|D|), O(n|Γ|L2ℓ2max) and O(nL|D|), where |Γ| is the number of input patterns.
In addition, we give an efficient algorithm for sampling. Finally, we consider the case of non-positive weights. (Komodakis & Paragios, 2009) gave an O(nL) algorithm for computing the MAP. We present a modification that has the same worst-case complexity but can beat it in the best case.
AU - Takhanov, Rustem
AU - Kolmogorov, Vladimir
ID - 2272
IS - 3
T2 - ICML'13 Proceedings of the 30th International Conference on International
TI - Inference algorithms for pattern-based CRFs on sequence data
VL - 28
ER -
TY - GEN
AB - We propose a new family of message passing techniques for MAP estimation in graphical models which we call Sequential Reweighted Message Passing (SRMP). Special cases include well-known techniques such as Min-Sum Diusion (MSD) and a faster Sequential Tree-Reweighted Message Passing (TRW-S). Importantly, our derivation is simpler than the original derivation of TRW-S, and does not involve a decomposition into trees. This allows easy generalizations. We present such a generalization for the case of higher-order graphical models, and test it on several real-world problems with promising results.
AU - Vladimir Kolmogorov
ID - 2273
TI - Reweighted message passing revisited
ER -
TY - GEN
AB - Proofs of work (PoW) have been suggested by Dwork and Naor (Crypto'92) as protection to a shared resource. The basic idea is to ask the service requestor to dedicate some non-trivial amount of computational work to every request. The original applications included prevention of spam and protection against denial of service attacks. More recently, PoWs have been used to prevent double spending in the Bitcoin digital currency system.
In this work, we put forward an alternative concept for PoWs -- so-called proofs of space (PoS), where a service requestor must dedicate a significant amount of disk space as opposed to computation. We construct secure PoS schemes in the random oracle model, using graphs with high "pebbling complexity" and Merkle hash-trees.
AU - Dziembowski, Stefan
AU - Faust, Sebastian
AU - Kolmogorov, Vladimir
AU - Pietrzak, Krzysztof Z
ID - 2274
TI - Proofs of Space
ER -
TY - CONF
AB - The problem of minimizing the Potts energy function frequently occurs in computer vision applications. One way to tackle this NP-hard problem was proposed by Kovtun [19, 20]. It identifies a part of an optimal solution by running k maxflow computations, where k is the number of labels. The number of “labeled” pixels can be significant in some applications, e.g. 50-93% in our tests for stereo. We show how to reduce the runtime to O (log k) maxflow computations (or one parametric maxflow computation). Furthermore, the output of our algorithm allows to speed-up the subsequent alpha expansion for the unlabeled part, or can be used as it is for time-critical applications. To derive our technique, we generalize the algorithm of Felzenszwalb et al. [7] for Tree Metrics . We also show a connection to k-submodular functions from combinatorial optimization, and discuss k-submodular relaxations for general energy functions.
AU - Gridchyn, Igor
AU - Kolmogorov, Vladimir
ID - 2276
TI - Potts model, parametric maxflow and k-submodular functions
ER -
TY - JOUR
AB - It is firmly established that interactions between neurons and glia are fundamental across species for the correct establishment of a functional brain. Here, we found that the glia of the Drosophila larval brain display an essential non-autonomous role during the development of the optic lobe. The optic lobe develops from neuroepithelial cells that proliferate by dividing symmetrically until they switch to asymmetric/differentiative divisions that generate neuroblasts. The proneural gene lethal of scute (l9sc) is transiently activated by the epidermal growth factor receptor (EGFR)-Ras signal transduction pathway at the leading edge of a proneural wave that sweeps from medial to lateral neuroepithelium, promoting this switch. This process is tightly regulated by the tissue-autonomous function within the neuroepithelium of multiple signaling pathways, including EGFR-Ras and Notch. This study shows that the Notch ligand Serrate (Ser) is expressed in the glia and it forms a complex in vivo with Notch and Canoe, which colocalize at the adherens junctions of neuroepithelial cells. This complex is crucial for interactions between glia and neuroepithelial cells during optic lobe development. Ser is tissue-autonomously required in the glia where it activates Notch to regulate its proliferation, and non-autonomously in the neuroepithelium where Ser induces Notch signaling to avoid the premature activation of the EGFR-Ras pathway and hence of L9sc. Interestingly, different Notch activity reporters showed very different expression patterns in the glia and in the neuroepithelium, suggesting the existence of tissue-specific factors that promote the expression of particular Notch target genes or/and a reporter response dependent on different thresholds of Notch signaling.
AU - Pérez Gómez, Raquel
AU - Slovakova, Jana
AU - Rives Quinto, Noemí
AU - Krejčí, Alena
AU - Carmena, Ana
ID - 2278
IS - 21
JF - Journal of Cell Science
TI - A serrate-notch-canoe complex mediates essential interactions between glia and neuroepithelial cells during Drosophila optic lobe development
VL - 126
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 - JOUR
AB - The problem of packing ellipsoids of different sizes and shapes into an ellipsoidal container so as to minimize a measure of overlap between ellipsoids is considered. A bilevel optimization formulation is given, together with an algorithm for the general case and a simpler algorithm for the special case in which all ellipsoids are in fact spheres. Convergence results are proved and computational experience is described and illustrated. The motivating application-chromosome organization in the human cell nucleus-is discussed briefly, and some illustrative results are presented.
AU - Uhler, Caroline
AU - Wright, Stephen
ID - 2280
IS - 4
JF - SIAM Review
TI - Packing ellipsoids with overlap
VL - 55
ER -
TY - JOUR
AB - Epithelial spreading is a common and fundamental aspect of various developmental and disease-related processes such as epithelial closure and wound healing. A key challenge for epithelial tissues undergoing spreading is to increase their surface area without disrupting epithelial integrity. Here we show that orienting cell divisions by tension constitutes an efficient mechanism by which the enveloping cell layer (EVL) releases anisotropic tension while undergoing spreading during zebrafish epiboly. The control of EVL cell-division orientation by tension involves cell elongation and requires myosin II activity to align the mitotic spindle with the main tension axis. We also found that in the absence of tension-oriented cell divisions and in the presence of increased tissue tension, EVL cells undergo ectopic fusions, suggesting that the reduction of tension anisotropy by oriented cell divisions is required to prevent EVL cells from fusing. We conclude that cell-division orientation by tension constitutes a key mechanism for limiting tension anisotropy and thus promoting tissue spreading during EVL epiboly.
AU - Campinho, Pedro
AU - Behrndt, Martin
AU - Ranft, Jonas
AU - Risler, Thomas
AU - Minc, Nicolas
AU - Heisenberg, Carl-Philipp J
ID - 2282
JF - Nature Cell Biology
TI - Tension-oriented cell divisions limit anisotropic tissue tension in epithelial spreading during zebrafish epiboly
VL - 15
ER -
TY - JOUR
AB - Pathogens exert a strong selection pressure on organisms to evolve effective immune defences. In addition to individual immunity, social organisms can act cooperatively to produce collective defences. In many ant species, queens have the option to found a colony alone or in groups with other, often unrelated, conspecifics. These associations are transient, usually lasting only as long as each queen benefits from the presence of others. In fact, once the first workers emerge, queens fight to the death for dominance. One potential advantage of co-founding may be that queens benefit from collective disease defences, such as mutual grooming, that act against common soil pathogens. We test this hypothesis by exposing single and co-founding queens to a fungal parasite, in order to assess whether queens in co-founding associations have improved survival. Surprisingly, co-foundresses exposed to the entomopathogenic fungus Metarhizium did not engage in cooperative disease defences, and consequently, we find no direct benefit of multiple queens on survival. However, an indirect benefit was observed, with parasite-exposed queens producing more brood when they co-founded, than when they were alone. We suggest this is due to a trade-off between reproduction and immunity. Additionally, we report an extraordinary ability of the queens to tolerate an infection for long periods after parasite exposure. Our study suggests that there are no social immunity benefits for co-founding ant queens, but that in parasite-rich environments, the presence of additional queens may nevertheless improve the chances of colony founding success.
AU - Pull, Christopher
AU - Hughes, William
AU - Brown, Markus
ID - 2283
IS - 12
JF - Naturwissenschaften
TI - Tolerating an infection: an indirect benefit of co-founding queen associations in the ant Lasius niger
VL - 100
ER -
TY - JOUR
AB - The spatiotemporal control of cell divisions is a key factor in epithelial morphogenesis and patterning. Mao et al (2013) now describe how differential rates of proliferation within the Drosophila wing disc epithelium give rise to anisotropic tissue tension in peripheral/proximal regions of the disc. Such global tissue tension anisotropy in turn determines the orientation of cell divisions by controlling epithelial cell elongation.
AU - Campinho, Pedro
AU - Heisenberg, Carl-Philipp J
ID - 2286
IS - 21
JF - EMBO Journal
TI - The force and effect of cell proliferation
VL - 32
ER -
TY - JOUR
AB - Negative frequency-dependent selection should result in equal sex ratios in large populations of dioecious flowering plants, but deviations from equality are commonly reported. A variety of ecological and genetic factors can explain biased sex ratios, although the mechanisms involved are not well understood. Most dioecious species are long-lived and/or clonal complicating efforts to identify stages during the life cycle when biases develop. We investigated the demographic correlates of sex-ratio variation in two chromosome races of Rumex hastatulus, an annual, wind-pollinated colonizer of open habitats from the southern USA. We examined sex ratios in 46 populations and evaluated the hypothesis that the proximity of males in the local mating environment, through its influence on gametophytic selection, is the primary cause of female-biased sex ratios. Female-biased sex ratios characterized most populations of R. hastatulus (mean sex ratio = 0.62), with significant female bias in 89% of populations. Large, high-density populations had the highest proportion of females, whereas smaller, low-density populations had sex ratios closer to equality. Progeny sex ratios were more female biased when males were in closer proximity to females, a result consistent with the gametophytic selection hypothesis. Our results suggest that interactions between demographic and genetic factors are probably the main cause of female-biased sex ratios in R. hastatulus. The annual life cycle of this species may limit the scope for selection against males and may account for the weaker degree of bias in comparison with perennial Rumex species.
AU - Pickup, Melinda
AU - Barrett, Spencer
ID - 2287
IS - 3
JF - Ecology and Evolution
TI - The influence of demography and local mating environment on sex ratios in a wind-pollinated dioecious plant
VL - 3
ER -
TY - GEN
AB - This book constitutes the proceedings of the 11th International Conference on Computational Methods in Systems Biology, CMSB 2013, held in Klosterneuburg, Austria, in September 2013. The 15 regular papers included in this volume were carefully reviewed and selected from 27 submissions. They deal with computational models for all levels, from molecular and cellular, to organs and entire organisms.
ED - Gupta, Ashutosh
ED - Henzinger, Thomas A
ID - 2288
SN - 978-3-642-40707-9
TI - Computational Methods in Systems Biology
VL - 8130
ER -
TY - JOUR
AB - Formal verification aims to improve the quality of software by detecting errors before they do harm. At the basis of formal verification is the logical notion of correctness, which purports to capture whether or not a program behaves as desired. We suggest that the boolean partition of software into correct and incorrect programs falls short of the practical need to assess the behavior of software in a more nuanced fashion against multiple criteria. We therefore propose to introduce quantitative fitness measures for programs, specifically for measuring the function, performance, and robustness of reactive programs such as concurrent processes. This article describes the goals of the ERC Advanced Investigator Project QUAREM. The project aims to build and evaluate a theory of quantitative fitness measures for reactive models. Such a theory must strive to obtain quantitative generalizations of the paradigms that have been success stories in qualitative reactive modeling, such as compositionality, property-preserving abstraction and abstraction refinement, model checking, and synthesis. The theory will be evaluated not only in the context of software and hardware engineering, but also in the context of systems biology. In particular, we will use the quantitative reactive models and fitness measures developed in this project for testing hypotheses about the mechanisms behind data from biological experiments.
AU - Henzinger, Thomas A
ID - 2289
IS - 4
JF - Computer Science Research and Development
TI - Quantitative reactive modeling and verification
VL - 28
ER -
TY - JOUR
AB - The plant hormone indole-acetic acid (auxin) is essential for many aspects of plant development. Auxin-mediated growth regulation typically involves the establishment of an auxin concentration gradient mediated by polarly localized auxin transporters. The localization of auxin carriers and their amount at the plasma membrane are controlled by membrane trafficking processes such as secretion, endocytosis, and recycling. In contrast to endocytosis or recycling, how the secretory pathway mediates the localization of auxin carriers is not well understood. In this study we have used the differential cell elongation process during apical hook development to elucidate the mechanisms underlying the post-Golgi trafficking of auxin carriers in Arabidopsis. We show that differential cell elongation during apical hook development is defective in Arabidopsis mutant echidna (ech). ECH protein is required for the trans-Golgi network (TGN)-mediated trafficking of the auxin influx carrier AUX1 to the plasma membrane. In contrast, ech mutation only marginally perturbs the trafficking of the highly related auxin influx carrier LIKE-AUX1-3 or the auxin efflux carrier PIN-FORMED-3, both also involved in hook development. Electron tomography reveals that the trafficking defects in ech mutant are associated with the perturbation of secretory vesicle genesis from the TGN. Our results identify differential mechanisms for the post-Golgi trafficking of de novo-synthesized auxin carriers to plasma membrane from the TGN and reveal how trafficking of auxin influx carriers mediates the control of differential cell elongation in apical hook development.
AU - Boutté, Yohann
AU - Jonsson, Kristoffer
AU - Mcfarlane, Heather
AU - Johnson, Errin
AU - Gendre, Delphine
AU - Swarup, Ranjan
AU - Friml, Jirí
AU - Samuels, Lacey
AU - Robert, Stéphanie
AU - Bhalerao, Rishikesh
ID - 2290
IS - 40
JF - PNAS
TI - ECHIDNA mediated post Golgi trafficking of auxin carriers for differential cell elongation
VL - 110
ER -
TY - CONF
AB - Cryptographic access control promises to offer easily distributed trust and broader applicability, while reducing reliance on low-level online monitors. Traditional implementations of cryptographic access control rely on simple cryptographic primitives whereas recent endeavors employ primitives with richer functionality and security guarantees. Worryingly, few of the existing cryptographic access-control schemes come with precise guarantees, the gap between the policy specification and the implementation being analyzed only informally, if at all. In this paper we begin addressing this shortcoming. Unlike prior work that targeted ad-hoc policy specification, we look at the well-established Role-Based Access Control (RBAC) model, as used in a typical file system. In short, we provide a precise syntax for a computational version of RBAC, offer rigorous definitions for cryptographic policy enforcement of a large class of RBAC security policies, and demonstrate that an implementation based on attribute-based encryption meets our security notions. We view our main contribution as being at the conceptual level. Although we work with RBAC for concreteness, our general methodology could guide future research for uses of cryptography in other access-control models.
AU - Ferrara, Anna
AU - Fuchsbauer, Georg
AU - Warinschi, Bogdan
ID - 2291
TI - Cryptographically enforced RBAC
ER -
TY - GEN
AB - This book constitutes the thoroughly refereed conference proceedings of the 38th International Symposium on Mathematical Foundations of Computer Science, MFCS 2013, held in Klosterneuburg, Austria, in August 2013. The 67 revised full papers presented together with six invited talks were carefully selected from 191 submissions. Topics covered include algorithmic game theory, algorithmic learning theory, algorithms and data structures, automata, formal languages, bioinformatics, complexity, computational geometry, computer-assisted reasoning, concurrency theory, databases and knowledge-based systems, foundations of computing, logic in computer science, models of computation, semantics and verification of programs, and theoretical issues in artificial intelligence.
ED - Chatterjee, Krishnendu
ED - Sgall, Jiri
ID - 2292
SN - 978-3-642-40312-5
TI - Mathematical Foundations of Computer Science 2013
VL - 8087
ER -
TY - CONF
AB - Many computer vision problems have an asymmetric distribution of information between training and test time. In this work, we study the case where we are given additional information about the training data, which however will not be available at test time. This situation is called learning using privileged information (LUPI). We introduce two maximum-margin techniques that are able to make use of this additional source of information, and we show that the framework is applicable to several scenarios that have been studied in computer vision before. Experiments with attributes, bounding boxes, image tags and rationales as additional information in object classification show promising results.
AU - Sharmanska, Viktoriia
AU - Quadrianto, Novi
AU - Lampert, Christoph
ID - 2293
TI - Learning to rank using privileged information
ER -
TY - CONF
AB - In this work we propose a system for automatic classification of Drosophila embryos into developmental stages.
While the system is designed to solve an actual problem in biological research, we believe that the principle underly-
ing it is interesting not only for biologists, but also for researchers in computer vision. The main idea is to combine two orthogonal sources of information: one is a classifier trained on strongly invariant features, which makes it applicable to images of very different conditions, but also leads to rather noisy predictions. The other is a label propagation step based on a more powerful similarity measure that however is only consistent within specific subsets of the data at a time.
In our biological setup, the information sources are the shape and the staining patterns of embryo images. We show
experimentally that while neither of the methods can be used by itself to achieve satisfactory results, their combina-
tion achieves prediction quality comparable to human performance.
AU - Kazmar, Tomas
AU - Kvon, Evgeny
AU - Stark, Alexander
AU - Lampert, Christoph
ID - 2294
TI - Drosophila Embryo Stage Annotation using Label Propagation
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 - JOUR
AB - We present an overview of mathematical results on the low temperature properties of dilute quantum gases, which have been obtained in the past few years. The presentation includes a discussion of Bose-Einstein condensation, the excitation spectrum for trapped gases and its relation to superfluidity, as well as the appearance of quantized vortices in rotating systems. All these properties are intensely being studied in current experiments on cold atomic gases. We will give a description of the mathematics involved in understanding these phenomena, starting from the underlying many-body Schrödinger equation.
AU - Seiringer, Robert
ID - 2297
IS - 2
JF - Japanese Journal of Mathematics
TI - Hot topics in cold gases: A mathematical physics perspective
VL - 8
ER -
TY - CONF
AB - We present a shape analysis for programs that manipulate overlaid data structures which share sets of objects. The abstract domain contains Separation Logic formulas that (1) combine a per-object separating conjunction with a per-field separating conjunction and (2) constrain a set of variables interpreted as sets of objects. The definition of the abstract domain operators is based on a notion of homomorphism between formulas, viewed as graphs, used recently to define optimal decision procedures for fragments of the Separation Logic. Based on a Frame Rule that supports the two versions of the separating conjunction, the analysis is able to reason in a modular manner about non-overlaid data structures and then, compose information only at a few program points, e.g., procedure returns. We have implemented this analysis in a prototype tool and applied it on several interesting case studies that manipulate overlaid and nested linked lists.
AU - Dragoi, Cezara
AU - Enea, Constantin
AU - Sighireanu, Mihaela
ID - 2298
TI - Local shape analysis for overlaid data structures
VL - 7935
ER -
TY - JOUR
AB - The standard hardware design flow involves: (a) design of an integrated circuit using a hardware description language, (b) extensive functional and formal verification, and (c) logical synthesis. However, the above-mentioned processes consume significant effort and time. An alternative approach is to use a formal specification language as a high-level hardware description language and synthesize hardware from formal specifications. Our work is a case study of the synthesis of the widely and industrially used AMBA AHB protocol from formal specifications. Bloem et al. presented the first formal specifications for the AMBA AHB Arbiter and synthesized the AHB Arbiter circuit. However, in the first formal specification some important assumptions were missing. Our contributions are as follows: (a) We present detailed formal specifications for the AHB Arbiter incorporating the missing details, and obtain significant improvements in the synthesis results (both with respect to the number of gates in the synthesized circuit and with respect to the time taken to synthesize the circuit), and (b) we present formal specifications to generate compact circuits for the remaining two main components of AMBA AHB, namely, AHB Master and AHB Slave. Thus with systematic description we are able to automatically and completely synthesize an important and widely used industrial protocol.
AU - Godhal, Yashdeep
AU - Chatterjee, Krishnendu
AU - Henzinger, Thomas A
ID - 2299
IS - 5-6
JF - International Journal on Software Tools for Technology Transfer
TI - Synthesis of AMBA AHB from formal specification: A case study
VL - 15
ER -
TY - JOUR
AB - We consider Ising models in two and three dimensions with nearest neighbor ferromagnetic interactions and long-range, power law decaying, antiferromagnetic interactions. If the strength of the ferromagnetic coupling J is larger than a critical value Jc, then the ground state is homogeneous and ferromagnetic. As the critical value is approached from smaller values of J, it is believed that the ground state consists of a periodic array of stripes (d=2) or slabs (d=3), all of the same size and alternating magnetization. Here we prove rigorously that the ground state energy per site converges to that of the optimal periodic striped or slabbed state, in the limit that J tends to the ferromagnetic transition point. While this theorem does not prove rigorously that the ground state is precisely striped or slabbed, it does prove that in any suitably large box the ground state is striped or slabbed with high probability.
AU - Giuliani, Alessandro
AU - Lieb, Élliott
AU - Seiringer, Robert
ID - 2300
IS - 6
JF - Physical Review B
TI - Realization of stripes and slabs in two and three dimensions
VL - 88
ER -
TY - CONF
AB - We describe the design and implementation of P, a domain-specific language to write asynchronous event driven code. P allows the programmer to specify the system as a collection of interacting state machines, which communicate with each other using events. P unifies modeling and programming into one activity for the programmer. Not only can a P program be compiled into executable code, but it can also be tested using model checking techniques. P allows the programmer to specify the environment, used to "close" the system during testing, as nondeterministic ghost machines. Ghost machines are erased during compilation to executable code; a type system ensures that the erasure is semantics preserving. The P language is designed so that a P program can be checked for responsiveness-the ability to handle every event in a timely manner. By default, a machine needs to handle every event that arrives in every state. But handling every event in every state is impractical. The language provides a notion of deferred events where the programmer can annotate when she wants to delay processing an event. The default safety checker looks for presence of unhan-dled events. The language also provides default liveness checks that an event cannot be potentially deferred forever. P was used to implement and verify the core of the USB device driver stack that ships with Microsoft Windows 8. The resulting driver is more reliable and performs better than its prior incarnation (which did not use P); we have more confidence in the robustness of its design due to the language abstractions and verification provided by P.
AU - Desai, Ankush
AU - Gupta, Vivek
AU - Jackson, Ethan
AU - Qadeer, Shaz
AU - Rajamani, Sriram
AU - Zufferey, Damien
ID - 2301
T2 - Proceedings of the 34th ACM SIGPLAN Conference on Programming Language Design and Implementation
TI - P: Safe asynchronous event-driven programming
ER -
TY - JOUR
AB - MADM (Mosaic Analysis with Double Markers) technology offers a genetic approach in mice to visualize and concomitantly manipulate genetically defined cells at clonal level and single cell resolution. MADM employs Cre recombinase/loxP-dependent interchromosomal mitotic recombination to reconstitute two split marker genes—green GFP and red tdTomato—and can label sparse clones of homozygous mutant cells in one color and wild-type cells in the other color in an otherwise unlabeled background. At present, major MADM applications include lineage tracing, single cell labeling, conditional knockouts in small populations of cells and induction of uniparental chromosome disomy to assess effects of genomic imprinting. MADM can be applied universally in the mouse with the sole limitation being the specificity of the promoter controlling Cre recombinase expression. Here I review recent developments and extensions of the MADM technique and give an overview of the major discoveries and progresses enabled by the implementation of the novel genetic MADM tools.
AU - Hippenmeyer, Simon
ID - 2303
IS - 6
JF - Frontiers in Biology
TI - Dissection of gene function at clonal level using mosaic analysis with double markers
VL - 8
ER -
TY - JOUR
AB - This extended abstract is concerned with the irregularities of distribution of one-dimensional permuted van der Corput sequences that are generated from linear permutations. We show how to obtain upper bounds for the discrepancy and diaphony of these sequences, by relating them to Kronecker sequences and applying earlier results of Faure and Niederreiter.
AU - Pausinger, Florian
ID - 2304
JF - Electronic Notes in Discrete Mathematics
TI - Van der Corput sequences and linear permutations
VL - 43
ER -
TY - CONF
AB - We study the complexity of central controller synthesis problems for finite-state Markov decision processes, where the objective is to optimize both the expected mean-payoff performance of the system and its stability. e argue that the basic theoretical notion of expressing the stability in terms of the variance of the mean-payoff (called global variance in our paper) is not always sufficient, since it ignores possible instabilities on respective runs. For this reason we propose alernative definitions of stability, which we call local and hybrid variance, and which express how rewards on each run deviate from the run's own mean-payoff and from the expected mean-payoff, respectively. We show that a strategy ensuring both the expected mean-payoff and the variance below given bounds requires randomization and memory, under all the above semantics of variance. We then look at the problem of determining whether there is a such a strategy. For the global variance, we show that the problem is in PSPACE, and that the answer can be approximated in pseudo-polynomial time. For the hybrid variance, the analogous decision problem is in NP, and a polynomial-time approximating algorithm also exists. For local variance, we show that the decision problem is in NP. Since the overall performance can be traded for stability (and vice versa), we also present algorithms for approximating the associated Pareto curve in all the three cases. Finally, we study a special case of the decision problems, where we require a given expected mean-payoff together with zero variance. Here we show that the problems can be all solved in polynomial time.
AU - Brázdil, Tomáš
AU - Chatterjee, Krishnendu
AU - Forejt, Vojtěch
AU - Kučera, Antonín
ID - 2305
T2 - 28th Annual ACM/IEEE Symposium
TI - Trading performance for stability in Markov decision processes
ER -
TY - BOOK
AB - Das Buch ist sowohl eine Einführung in die Themen Linked Data, Open Data und Open Linked Data als es auch den konkreten Bezug auf Bibliotheken behandelt. Hierzu werden konkrete Anwendungsprojekte beschrieben. Der Band wendet sich dabei sowohl an Personen aus der Bibliothekspraxis als auch an Personen aus dem Bibliotheksmanagement, die noch nicht mit dem Thema vertraut sind.
AU - Danowski, Patrick
AU - Pohl, Adrian
ID - 2306
SN - 2191-3587
TI - (Open) Linked Data in Bibliotheken
VL - 50
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 - CONF
AB - Linearizability of concurrent data structures is usually proved by monolithic simulation arguments relying on identifying the so-called linearization points. Regrettably, such proofs, whether manual or automatic, are often complicated and scale poorly to advanced non-blocking concurrency patterns, such as helping and optimistic updates.
In response, we propose a more modular way of checking linearizability of concurrent queue algorithms that does not involve identifying linearization points. We reduce the task of proving linearizability with respect to the queue specification to establishing four basic properties, each of which can be proved independently by simpler arguments. As a demonstration of our approach, we verify the Herlihy and Wing queue, an algorithm that is challenging to verify by a simulation proof.
AU - Henzinger, Thomas A
AU - Sezgin, Ali
AU - Vafeiadis, Viktor
ID - 2328
TI - Aspect-oriented linearizability proofs
VL - 8052
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 -