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 - 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 - 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 - Background: Monoclonal antibodies (mAb), such as trastuzumab are a valuable addition to breast cancer therapy.
Data obtained from neoadjuvant settings revealed that antibody-dependent cell-mediated cytotoxicity (ADCC) is a
major mechanism of action for the mAb trastuzumab. Conflicting results still call into question whether disease
progression, prolonged treatment or concomitant chemotherapy influences ADCC and related immunological
phenomena.
Methods: We analyzed the activity of ADCC and antibody-dependent cell-mediated phagocytosis (ADCP) of
peripheral blood mononuclear cells (PBMCs) from human epidermal growth factor receptor 2 (HER2/neu) positive
breast cancer patients receiving trastuzumab therapy either in an adjuvant (n = 13) or metastatic (n = 15) setting as
well as from trastuzumab treatment-naive (t-naive) HER2/neu negative patients (n = 15). PBMCs from healthy volunteers
(n = 24) were used as controls. ADCC and ADCP activity was correlated with the expression of antibody binding
Fc-gamma receptor (FcγR)I (CD64), FcγRII (CD32) and FcγRIII (CD16) on CD14+ (monocytes) and CD56+ (NK) cells, as well as the expression of CD107a+ (LAMP-1) on CD56+ cells and the total amount of CD4+CD25+FOXP3+ (Treg) cells. In metastatic patients, markers were correlated with progression-free survival (PFS).
Results: ADCC activity was significantly down regulated in metastatic, adjuvant and t-naive patient cohorts as compared to healthy controls. Reduced ADCC activity was inversely correlated with the expression of CD107a on CD56+
cells in adjuvant patients. ADCC and ADCP activity of the patient cohorts were similar, regardless of treatment duration
or additional chemotherapy. PFS in metastatic patients inversely correlated with the number of peripheral Treg cells.
Conclusion: The reduction of ADCC in patients as compared to healthy controls calls for adjuvant strategies, such as
immune-enhancing agents, to improve the activity of trastuzumab. However, efficacy of trastuzumab-specific ADCC
and ADCP appears not to be affected by treatment duration, disease progression or concomitant chemotherapy. This
finding supports the application of trastuzumab at any stage of the disease.
AU - Petricevic, Branka
AU - Laengle, Johannes
AU - Singer, Josef
AU - Sachet, Monika
AU - Fazekas, Judit
AU - Steger, Guenther
AU - Bartsch, Rupert
AU - Jensen-Jarolim, Erika
AU - Bergmann, Michael
ID - 8245
JF - Journal of Translational Medicine
SN - 1479-5876
TI - Trastuzumab mediates antibody-dependent cell-mediated cytotoxicity and phagocytosis to the same extent in both adjuvant and metastatic HER2/neu breast cancer patients
VL - 11
ER -
TY - JOUR
AB - As sessile organisms, plants have to be able to adapt to a continuously changing environment. Plants that perceive some of these changes as stress signals activate signaling pathways to modulate their development and to enable them to survive. The complex responses to environmental cues are to a large extent mediated by plant hormones that together orchestrate the final plant response. The phytohormone cytokinin is involved in many plant developmental processes. Recently, it has been established that cytokinin plays an important role in stress responses, but does not act alone. Indeed, the hormonal control of plant development and stress adaptation is the outcome of a complex network of multiple synergistic and antagonistic interactions between various hormones. Here, we review the recent findings on the cytokinin function as part of this hormonal network. We focus on the importance of the crosstalk between cytokinin and other hormones, such as abscisic acid, jasmonate, salicylic acid, ethylene, and auxin in the modulation of plant development and stress adaptation. Finally, the impact of the current research in the biotechnological industry will be discussed.
AU - O'Brien, José
AU - Benková, Eva
ID - 827
JF - Frontiers in Plant Science
TI - Cytokinin cross talking during biotic and abiotic stress responses
VL - 4
ER -
TY - JOUR
AB - The plant root system is essential for providing anchorage to the soil, supplying minerals and water, and synthesizing metabolites. It is a dynamic organ modulated by external cues such as environmental signals, water and nutrients availability, salinity and others. Lateral roots (LRs) are initiated from the primary root post-embryonically, after which they progress through discrete developmental stages which can be independently controlled, providing a high level of plasticity during root system formation. Within this review, main contributions are presented, from the classical forward genetic screens to the more recent high-throughput approaches, combined with computer model predictions, dissecting how LRs and thereby root system architecture is established and developed.
AU - Cuesta, Candela
AU - Wabnik, Krzysztof T
AU - Benková, Eva
ID - 828
JF - Frontiers in Plant Science
TI - Systems approaches to study root architecture dynamics
VL - 4
ER -
TY - CONF
AB - 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 - 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 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 - 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 - JOUR
AB - Maternal exposure to infection occurring mid-gestation produces a three-fold increase in the risk of schizophrenia in the offspring. The critical initiating factor appears to be the maternal immune activation (MIA) that follows infection. This process can be induced in rodents by exposure of pregnant dams to the viral mimic Poly I:C, which triggers an immune response that results in structural, functional, behavioral, and electrophysiological phenotypes in the adult offspring that model those seen in schizophrenia. We used this model to explore the role of synchronization in brain neural networks, a process thought to be dysfunctional in schizophrenia and previously associated with positive, negative, and cognitive symptoms of schizophrenia. Exposure of pregnant dams to Poly I:C on GD15 produced an impairment in long-range neural synchrony in adult offspring between two regions implicated in schizophrenia pathology; the hippocampus and the medial prefrontal cortex (mPFC). This reduction in synchrony was ameliorated by acute doses of the antipsychotic clozapine. MIA animals have previously been shown to have impaired pre-pulse inhibition (PPI), a gold-standard measure of schizophrenia-like deficits in animal models. Our data showed that deficits in synchrony were positively correlated with the impairments in PPI. Subsequent analysis of LFP activity during the PPI response also showed that reduced coupling between the mPFC and the hippocampus following processing of the pre-pulse was associated with reduced PPI. The ability of the MIA intervention to model neurodevelopmental aspects of schizophrenia pathology provides a useful platform from which to investigate the ontogeny of aberrant synchronous processes. Further, the way in which the model expresses translatable deficits such as aberrant synchrony and reduced PPI will allow researchers to explore novel intervention strategies targeted to these changes.
AU - Dickerson, Desiree
AU - Bilkey, David
ID - 476
IS - DEC
JF - Frontiers in Behavioral Neuroscience
TI - Aberrant neural synchrony in the maternal immune activation model: Using translatable measures to explore targeted interventions
VL - 7
ER -
TY - JOUR
AB - Background: Reassortment between the RNA segments encoding haemagglutinin (HA) and neuraminidase (NA), the major antigenic influenza proteins, produces viruses with novel HA and NA subtype combinations and has preceded the emergence of pandemic strains. It has been suggested that productive viral infection requires a balance in the level of functional activity of HA and NA, arising from their closely interacting roles in the viral life cycle, and that this functional balance could be mediated by genetic changes in the HA and NA. Here, we investigate how the selective pressure varies for H7 avian influenza HA on different NA subtype backgrounds. Results: By extending Bayesian stochastic mutational mapping methods to calculate the ratio of the rate of non-synonymous change to the rate of synonymous change (d N/d S), we found the average d N/d S across the avian influenza H7 HA1 region to be significantly greater on an N2 NA subtype background than on an N1, N3 or N7 background. Observed differences in evolutionary rates of H7 HA on different NA subtype backgrounds could not be attributed to underlying differences between avian host species or virus pathogenicity. Examination of d N/d S values for each subtype on a site-by-site basis indicated that the elevated d N/d S on the N2 NA background was a result of increased selection, rather than a relaxation of selective constraint. Conclusions: Our results are consistent with the hypothesis that reassortment exposes influenza HA to significant changes in selective pressure through genetic interactions with NA. Such epistatic effects might be explicitly accounted for in future models of influenza evolution.
AU - Ward, Melissa
AU - Lycett, Samantha
AU - Avila, Dorita
AU - Bollback, Jonathan P
AU - Leigh Brown, Andrew
ID - 500
IS - 1
JF - BMC Evolutionary Biology
TI - Evolutionary interactions between haemagglutinin and neuraminidase in avian influenza
VL - 13
ER -
TY - JOUR
AB - All known species of extant tapirs are allopatric: 1 in southeastern Asia and 3 in Central and South America. The fossil record for tapirs, however, is much wider in geographical range, including Europe, Asia, and North and South America, going back to the late Oligocene, making the present distribution a relict of the original one. We here describe a new species of living Tapirus from the Amazon rain forest, the 1st since T. bairdii Gill, 1865, and the 1st new Perissodactyla in more than 100 years, from both morphological and molecular characters. It is shorter in stature than T. terrestris (Linnaeus, 1758) and has distinctive skull morphology, and it is basal to the clade formed by T. terrestris and T. pinchaque (Roulin, 1829). This highlights the unrecognized biodiversity in western Amazonia, where the biota faces increasing threats. Local peoples have long recognized our new species, suggesting a key role for traditional knowledge in understanding the biodiversity of the region.
AU - Cozzuol, Mario
AU - Clozato, Camila
AU - Holanda, Elizete
AU - Rodrigues, Flávio
AU - Nienow, Samuel
AU - De Thoisy, Benoit
AU - Fernandes Redondo, Rodrigo A
AU - Santos, Fabrício
ID - 501
IS - 6
JF - Journal of Mammalogy
TI - A new species of tapir from the Amazon
VL - 94
ER -
TY - JOUR
AB - 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 - 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 - 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 - 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 - 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 - 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 - 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 - CONF
AB - Depth-Bounded Systems form an expressive class of well-structured transition systems. They can model a wide range of concurrent infinite-state systems including those with dynamic thread creation, dynamically changing communication topology, and complex shared heap structures. We present the first method to automatically prove fair termination of depth-bounded systems. Our method uses a numerical abstraction of the system, which we obtain by systematically augmenting an over-approximation of the system’s reachable states with a finite set of counters. This numerical abstraction can be analyzed with existing termination provers. What makes our approach unique is the way in which it exploits the well-structuredness of the analyzed system. We have implemented our work in a prototype tool and used it to automatically prove liveness properties of complex concurrent systems, including nonblocking algorithms such as Treiber’s stack and several distributed processes. Many of these examples are beyond the scope of termination analyses that are based on traditional counter abstractions.
AU - Bansal, Kshitij
AU - Koskinen, Eric
AU - Wies, Thomas
AU - Zufferey, Damien
ED - Piterman, Nir
ED - Smolka, Scott
ID - 2847
TI - Structural Counter Abstraction
VL - 7795
ER -
TY - CONF
AB - We develop program synthesis techniques that can help programmers fix concurrency-related bugs. We make two new contributions to synthesis for concurrency, the first improving the efficiency of the synthesized code, and the second improving the efficiency of the synthesis procedure itself. The first contribution is to have the synthesis procedure explore a variety of (sequential) semantics-preserving program transformations. Classically, only one such transformation has been considered, namely, the insertion of synchronization primitives (such as locks). Based on common manual bug-fixing techniques used by Linux device-driver developers, we explore additional, more efficient transformations, such as the reordering of independent instructions. The second contribution is to speed up the counterexample-guided removal of concurrency bugs within the synthesis procedure by considering partial-order traces (instead of linear traces) as counterexamples. A partial-order error trace represents a set of linear (interleaved) traces of a concurrent program all of which lead to the same error. By eliminating a partial-order error trace, we eliminate in a single iteration of the synthesis procedure all linearizations of the partial-order trace. We evaluated our techniques on several simplified examples of real concurrency bugs that occurred in Linux device drivers.
AU - Cerny, Pavol
AU - Henzinger, Thomas A
AU - Radhakrishna, Arjun
AU - Ryzhyk, Leonid
AU - Tarrach, Thorsten
ID - 2445
TI - Efficient synthesis for concurrency by semantics-preserving transformations
VL - 8044
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 -