TY - JOUR
AB - The ability to escape apoptosis is a hallmark of cancer-initiating cells and a key factor of resistance to oncolytic therapy. Here, we identify FAM96A as a ubiquitous, evolutionarily conserved apoptosome-activating protein and investigate its potential pro-apoptotic tumor suppressor function in gastrointestinal stromal tumors (GISTs). Interaction between FAM96A and apoptotic peptidase activating factor 1 (APAF1) was identified in yeast two-hybrid screen and further studied by deletion mutants, glutathione-S-transferase pull-down, co-immunoprecipitation and immunofluorescence. Effects of FAM96A overexpression and knock-down on apoptosis sensitivity were examined in cancer cells and zebrafish embryos. Expression of FAM96A in GISTs and histogenetically related cells including interstitial cells of Cajal (ICCs), “fibroblast-like cells” (FLCs) and ICC stem cells (ICC-SCs) was investigated by Northern blotting, reverse transcription—polymerase chain reaction, immunohistochemistry and Western immunoblotting. Tumorigenicity of GIST cells and transformed murine ICC-SCs stably transduced to re-express FAM96A was studied by xeno- and allografting into immunocompromised mice. FAM96A was found to bind APAF1 and to enhance the induction of mitochondrial apoptosis. FAM96A protein or mRNA was dramatically reduced or lost in 106 of 108 GIST samples representing three independent patient cohorts. Whereas ICCs, ICC-SCs and FLCs, the presumed normal counterparts of GIST, were found to robustly express FAM96A protein and mRNA, FAM96A expression was much reduced in tumorigenic ICC-SCs. Re-expression of FAM96A in GIST cells and transformed ICC-SCs increased apoptosis sensitivity and diminished tumorigenicity. Our data suggest FAM96A is a novel pro-apoptotic tumor suppressor that is lost during GIST tumorigenesis.
AU - Schwamb, Bettina
AU - Pick, Robert
AU - Fernández, Sara
AU - Völp, Kirsten
AU - Heering, Jan
AU - Dötsch, Volker
AU - Bösser, Susanne
AU - Jung, Jennifer
AU - Beinoravičiute Kellner, Rasa
AU - Wesely, Josephine
AU - Zörnig, Inka
AU - Hammerschmidt, Matthias
AU - Nowak, Matthias
AU - Penzel, Roland
AU - Zatloukal, Kurt
AU - Joos, Stefan
AU - Rieker, Ralf
AU - Agaimy, Abbas
AU - Söder, Stephan
AU - Reid Lombardo, Kmarie
AU - Kendrick, Michael
AU - Bardsley, Michael
AU - Hayashi, Yujiro
AU - Asuzu, David
AU - Syed, Sabriya
AU - Ördög, Tamás
AU - Zörnig, Martin
ID - 1848
IS - 6
JF - International Journal of Cancer
TI - FAM96A is a novel pro-apoptotic tumor suppressor in gastrointestinal stromal tumors
VL - 137
ER -
TY - JOUR
AB - Cell polarity is a fundamental property of pro- and eukaryotic cells. It is necessary for coordination of cell division, cell morphogenesis and signaling processes. How polarity is generated and maintained is a complex issue governed by interconnected feed-back regulations between small GTPase signaling and membrane tension-based signaling that controls membrane trafficking, and cytoskeleton organization and dynamics. Here, we will review the potential role for calcium as a crucial signal that connects and coordinates the respective processes during polarization processes in plants. This article is part of a Special Issue entitled: 13th European Symposium on Calcium.
AU - Himschoot, Ellie
AU - Beeckman, Tom
AU - Friml, Jiřĺ
AU - Vanneste, Steffen
ID - 1849
IS - 9
JF - Biochimica et Biophysica Acta - Molecular Cell Research
TI - Calcium is an organizer of cell polarity in plants
VL - 1853
ER -
TY - JOUR
AB - Entomopathogenic fungi are potent biocontrol agents that are widely used against insect pests, many of which are social insects. Nevertheless, theoretical investigations of their particular life history are scarce. We develop a model that takes into account the main distinguishing features between traditionally studied diseases and obligate killing pathogens, like the (biocontrol-relevant) insect-pathogenic fungi Metarhizium and Beauveria. First, obligate killing entomopathogenic fungi produce new infectious particles (conidiospores) only after host death and not yet on the living host. Second, the killing rates of entomopathogenic fungi depend strongly on the initial exposure dosage, thus we explicitly consider the pathogen load of individual hosts. Further, we make the model applicable not only to solitary host species, but also to group living species by incorporating social interactions between hosts, like the collective disease defences of insect societies. Our results identify the optimal killing rate for the pathogen that minimises its invasion threshold. Furthermore, we find that the rate of contact between hosts has an ambivalent effect: dense interaction networks between individuals are considered to facilitate disease outbreaks because of increased pathogen transmission. In social insects, this is compensated by their collective disease defences, i.e., social immunity. For the type of pathogens considered here, we show that even without social immunity, high contact rates between live individuals dilute the pathogen in the host colony and hence can reduce individual pathogen loads below disease-causing levels.
AU - Novak, Sebastian
AU - Cremer, Sylvia
ID - 1850
IS - 5
JF - Journal of Theoretical Biology
TI - Fungal disease dynamics in insect societies: Optimal killing rates and the ambivalent effect of high social interaction rates
VL - 372
ER -
TY - JOUR
AB - We consider mating strategies for females who search for males sequentially during a season of limited length. We show that the best strategy rejects a given male type if encountered before a time-threshold but accepts him after. For frequency-independent benefits, we obtain the optimal time-thresholds explicitly for both discrete and continuous distributions of males, and allow for mistakes being made in assessing the correct male type. When the benefits are indirect (genes for the offspring) and the population is under frequency-dependent ecological selection, the benefits depend on the mating strategy of other females as well. This case is particularly relevant to speciation models that seek to explore the stability of reproductive isolation by assortative mating under frequency-dependent ecological selection. We show that the indirect benefits are to be quantified by the reproductive values of couples, and describe how the evolutionarily stable time-thresholds can be found. We conclude with an example based on the Levene model, in which we analyze the evolutionarily stable assortative mating strategies and the strength of reproductive isolation provided by them.
AU - Priklopil, Tadeas
AU - Kisdi, Eva
AU - Gyllenberg, Mats
ID - 1851
IS - 4
JF - Evolution
TI - Evolutionarily stable mating decisions for sequentially searching females and the stability of reproductive isolation by assortative mating
VL - 69
ER -
TY - JOUR
AB - Summary: Declining populations of bee pollinators are a cause of concern, with major repercussions for biodiversity loss and food security. RNA viruses associated with honeybees represent a potential threat to other insect pollinators, but the extent of this threat is poorly understood. This study aims to attain a detailed understanding of the current and ongoing risk of emerging infectious disease (EID) transmission between managed and wild pollinator species across a wide range of RNA viruses. Within a structured large-scale national survey across 26 independent sites, we quantify the prevalence and pathogen loads of multiple RNA viruses in co-occurring managed honeybee (Apis mellifera) and wild bumblebee (Bombus spp.) populations. We then construct models that compare virus prevalence between wild and managed pollinators. Multiple RNA viruses associated with honeybees are widespread in sympatric wild bumblebee populations. Virus prevalence in honeybees is a significant predictor of virus prevalence in bumblebees, but we remain cautious in speculating over the principle direction of pathogen transmission. We demonstrate species-specific differences in prevalence, indicating significant variation in disease susceptibility or tolerance. Pathogen loads within individual bumblebees may be high and in the case of at least one RNA virus, prevalence is higher in wild bumblebees than in managed honeybee populations. Our findings indicate widespread transmission of RNA viruses between managed and wild bee pollinators, pointing to an interconnected network of potential disease pressures within and among pollinator species. In the context of the biodiversity crisis, our study emphasizes the importance of targeting a wide range of pathogens and defining host associations when considering potential drivers of population decline.
AU - Mcmahon, Dino
AU - Fürst, Matthias
AU - Caspar, Jesicca
AU - Theodorou, Panagiotis
AU - Brown, Mark
AU - Paxton, Robert
ID - 1855
IS - 3
JF - Journal of Animal Ecology
TI - A sting in the spit: Widespread cross-infection of multiple RNA viruses across wild and managed bees
VL - 84
ER -
TY - JOUR
AB - The traditional synthesis question given a specification asks for the automatic construction of a system that satisfies the specification, whereas often there exists a preference order among the different systems that satisfy the given specification. Under a probabilistic assumption about the possible inputs, such a preference order is naturally expressed by a weighted automaton, which assigns to each word a value, such that a system is preferred if it generates a higher expected value. We solve the following optimal synthesis problem: given an omega-regular specification, a Markov chain that describes the distribution of inputs, and a weighted automaton that measures how well a system satisfies the given specification under the input assumption, synthesize a system that optimizes the measured value. For safety specifications and quantitative measures that are defined by mean-payoff automata, the optimal synthesis problem reduces to finding a strategy in a Markov decision process (MDP) that is optimal for a long-run average reward objective, which can be achieved in polynomial time. For general omega-regular specifications along with mean-payoff automata, the solution rests on a new, polynomial-time algorithm for computing optimal strategies in MDPs with mean-payoff parity objectives. Our algorithm constructs optimal strategies that consist of two memoryless strategies and a counter. The counter is in general not bounded. To obtain a finite-state system, we show how to construct an ε-optimal strategy with a bounded counter, for all ε > 0. Furthermore, we show how to decide in polynomial time if it is possible to construct an optimal finite-state system (i.e., a system without a counter) for a given specification. We have implemented our approach and the underlying algorithms in a tool that takes qualitative and quantitative specifications and automatically constructs a system that satisfies the qualitative specification and optimizes the quantitative specification, if such a system exists. We present some experimental results showing optimal systems that were automatically generated in this way.
AU - Chatterjee, Krishnendu
AU - Henzinger, Thomas A
AU - Jobstmann, Barbara
AU - Singh, Rohit
ID - 1856
IS - 1
JF - Journal of the ACM
TI - Measuring and synthesizing systems in probabilistic environments
VL - 62
ER -
TY - CONF
AB - Sharing information between multiple tasks enables algorithms to achieve good generalization performance even from small amounts of training data. However, in a realistic scenario of multi-task learning not all tasks are equally related to each other, hence it could be advantageous to transfer information only between the most related tasks. In this work we propose an approach that processes multiple tasks in a sequence with sharing between subsequent tasks instead of solving all tasks jointly. Subsequently, we address the question of curriculum learning of tasks, i.e. finding the best order of tasks to be learned. Our approach is based on a generalization bound criterion for choosing the task order that optimizes the average expected classification performance over all tasks. Our experimental results show that learning multiple related tasks sequentially can be more effective than learning them jointly, the order in which tasks are being solved affects the overall performance, and that our model is able to automatically discover the favourable order of tasks.
AU - Pentina, Anastasia
AU - Sharmanska, Viktoriia
AU - Lampert, Christoph
ID - 1857
TI - Curriculum learning of multiple tasks
ER -
TY - CONF
AB - We study the problem of predicting the future, though only in the probabilistic sense of estimating a future state of a time-varying probability distribution. This is not only an interesting academic problem, but solving this extrapolation problem also has many practical application, e.g. for training classifiers that have to operate under time-varying conditions. Our main contribution is a method for predicting the next step of the time-varying distribution from a given sequence of sample sets from earlier time steps. For this we rely on two recent machine learning techniques: embedding probability distributions into a reproducing kernel Hilbert space, and learning operators by vector-valued regression. We illustrate the working principles and the practical usefulness of our method by experiments on synthetic and real data. We also highlight an exemplary application: training a classifier in a domain adaptation setting without having access to examples from the test time distribution at training time.
AU - Lampert, Christoph
ID - 1858
TI - Predicting the future behavior of a time-varying probability distribution
ER -
TY - CONF
AB - Structural support vector machines (SSVMs) are amongst the best performing models for structured computer vision tasks, such as semantic image segmentation or human pose estimation. Training SSVMs, however, is computationally costly, because it requires repeated calls to a structured prediction subroutine (called \emph{max-oracle}), which has to solve an optimization problem itself, e.g. a graph cut.
In this work, we introduce a new algorithm for SSVM training that is more efficient than earlier techniques when the max-oracle is computationally expensive, as it is frequently the case in computer vision tasks. The main idea is to (i) combine the recent stochastic Block-Coordinate Frank-Wolfe algorithm with efficient hyperplane caching, and (ii) use an automatic selection rule for deciding whether to call the exact max-oracle or to rely on an approximate one based on the cached hyperplanes.
We show experimentally that this strategy leads to faster convergence to the optimum with respect to the number of requires oracle calls, and that this translates into faster convergence with respect to the total runtime when the max-oracle is slow compared to the other steps of the algorithm.
AU - Shah, Neel
AU - Kolmogorov, Vladimir
AU - Lampert, Christoph
ID - 1859
TI - A multi-plane block-coordinate Frank-Wolfe algorithm for training structural SVMs with a costly max-oracle
ER -
TY - CONF
AB - Classifiers for object categorization are usually evaluated by their accuracy on a set of i.i.d. test examples. This provides us with an estimate of the expected error when applying the classifiers to a single new image. In real application, however, classifiers are rarely only used for a single image and then discarded. Instead, they are applied sequentially to many images, and these are typically not i.i.d. samples from a fixed data distribution, but they carry dependencies and their class distribution varies over time. In this work, we argue that the phenomenon of correlated data at prediction time is not a nuisance, but a blessing in disguise. We describe a probabilistic method for adapting classifiers at prediction time without having to retrain them. We also introduce a framework for creating realistically distributed image sequences, which offers a way to benchmark classifier adaptation methods, such as the one we propose. Experiments on the ILSVRC2010 and ILSVRC2012 datasets show that adapting object classification systems at prediction time can significantly reduce their error rate, even with no additional human feedback.
AU - Royer, Amélie
AU - Lampert, Christoph
ID - 1860
TI - Classifier adaptation at prediction time
ER -
TY - JOUR
AB - Continuous-time Markov chains are commonly used in practice for modeling biochemical reaction networks in which the inherent randomness of themolecular interactions cannot be ignored. This has motivated recent research effort into methods for parameter inference and experiment design for such models. The major difficulty is that such methods usually require one to iteratively solve the chemical master equation that governs the time evolution of the probability distribution of the system. This, however, is rarely possible, and even approximation techniques remain limited to relatively small and simple systems. An alternative explored in this article is to base methods on only some low-order moments of the entire probability distribution. We summarize the theory behind such moment-based methods for parameter inference and experiment design and provide new case studies where we investigate their performance.
AU - Ruess, Jakob
AU - Lygeros, John
ID - 1861
IS - 2
JF - ACM Transactions on Modeling and Computer Simulation
TI - Moment-based methods for parameter inference and experiment design for stochastic biochemical reaction networks
VL - 25
ER -
TY - JOUR
AB - The Altshuler–Shklovskii formulas (Altshuler and Shklovskii, BZh Eksp Teor Fiz 91:200, 1986) predict, for any disordered quantum system in the diffusive regime, a universal power law behaviour for the correlation functions of the mesoscopic eigenvalue density. In this paper and its companion (Erdős and Knowles, The Altshuler–Shklovskii formulas for random band matrices I: the unimodular case, 2013), we prove these formulas for random band matrices. In (Erdős and Knowles, The Altshuler–Shklovskii formulas for random band matrices I: the unimodular case, 2013) we introduced a diagrammatic approach and presented robust estimates on general diagrams under certain simplifying assumptions. In this paper, we remove these assumptions by giving a general estimate of the subleading diagrams. We also give a precise analysis of the leading diagrams which give rise to the Altschuler–Shklovskii power laws. Moreover, we introduce a family of general random band matrices which interpolates between real symmetric (β = 1) and complex Hermitian (β = 2) models, and track the transition for the mesoscopic density–density correlation. Finally, we address the higher-order correlation functions by proving that they behave asymptotically according to a Gaussian process whose covariance is given by the Altshuler–Shklovskii formulas.
AU - Erdös, László
AU - Knowles, Antti
ID - 1864
IS - 3
JF - Annales Henri Poincare
TI - The Altshuler–Shklovskii formulas for random band matrices II: The general case
VL - 16
ER -
TY - JOUR
AB - The plant hormone auxin and its directional transport are known to play a crucial role in defining the embryonic axis and subsequent development of the body plan. Although the role of PIN auxin efflux transporters has been clearly assigned during embryonic shoot and root specification, the role of the auxin influx carriers AUX1 and LIKE-AUX1 (LAX) proteins is not well established. Here, we used chemical and genetic tools on Brassica napus microspore-derived embryos and Arabidopsis thaliana zygotic embryos, and demonstrate that AUX1, LAX1 and LAX2 are required for both shoot and root pole formation, in concert with PIN efflux carriers. Furthermore, we uncovered a positive-feedback loop betweenMONOPTEROS(ARF5)-dependent auxin signalling and auxin transport. ThisMONOPTEROSdependent transcriptional regulation of auxin influx (AUX1, LAX1 and LAX2) and auxin efflux (PIN1 and PIN4) carriers by MONOPTEROS helps to maintain proper auxin transport to the root tip. These results indicate that auxin-dependent cell specification during embryo development requires balanced auxin transport involving both influx and efflux mechanisms, and that this transport is maintained by a positive transcriptional feedback on auxin signalling.
AU - Robert, Hélène
AU - Grunewald, Wim
AU - Sauer, Michael
AU - Cannoot, Bernard
AU - Soriano, Mercedes
AU - Swarup, Ranjan
AU - Weijers, Dolf
AU - Bennett, Malcolm
AU - Boutilier, Kim
AU - Friml, Jirí
ID - 1865
IS - 4
JF - Development
TI - Plant embryogenesis requires AUX/LAX-mediated auxin influx
VL - 142
ER -
TY - JOUR
AU - Henzinger, Thomas A
AU - Raskin, Jean
ID - 1866
IS - 2
JF - Communications of the ACM
TI - The equivalence problem for finite automata: Technical perspective
VL - 58
ER -
TY - JOUR
AB - Cultured mammalian cells essential are model systems in basic biology research, production platforms of proteins for medical use, and testbeds in synthetic biology. Flavin cofactors, in particular flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), are critical for cellular redox reactions and sense light in naturally occurring photoreceptors and optogenetic tools. Here, we quantified flavin contents of commonly used mammalian cell lines. We first compared three procedures for extraction of free and noncovalently protein-bound flavins and verified extraction using fluorescence spectroscopy. For separation, two CE methods with different BGEs were established, and detection was performed by LED-induced fluorescence with limit of detections (LODs 0.5-3.8 nM). We found that riboflavin (RF), FMN, and FAD contents varied significantly between cell lines. RF (3.1-14 amol/cell) and FAD (2.2-17.0 amol/cell) were the predominant flavins, while FMN (0.46-3.4 amol/cell) was found at markedly lower levels. Observed flavin contents agree with those previously extracted from mammalian tissues, yet reduced forms of RF were detected that were not described previously. Quantification of flavins in mammalian cell lines will allow a better understanding of cellular redox reactions and optogenetic tools.
AU - Hühner, Jens
AU - Inglés Prieto, Álvaro
AU - Neusüß, Christian
AU - Lämmerhofer, Michael
AU - Janovjak, Harald L
ID - 1867
IS - 4
JF - Electrophoresis
TI - Quantification of riboflavin, flavin mononucleotide, and flavin adenine dinucleotide in mammalian model cells by CE with LED-induced fluorescence detection
VL - 36
ER -
TY - JOUR
AB - We investigate high-dimensional nonlinear dynamical systems exhibiting multiple resonances under adiabatic parameter variations. Our motivations come from experimental considerations where time-dependent sweeping of parameters is a practical approach to probing and characterizing the bifurcations of the system. The question is whether bifurcations so detected are faithful representations of the bifurcations intrinsic to the original stationary system. Utilizing a harmonically forced, closed fluid flow system that possesses multiple resonances and solving the Navier-Stokes equation under proper boundary conditions, we uncover the phenomenon of the early effect. Specifically, as a control parameter, e.g., the driving frequency, is adiabatically increased from an initial value, resonances emerge at frequency values that are lower than those in the corresponding stationary system. The phenomenon is established by numerical characterization of physical quantities through the resonances, which include the kinetic energy and the vorticity field, and a heuristic analysis based on the concept of instantaneous frequency. A simple formula is obtained which relates the resonance points in the time-dependent and time-independent systems. Our findings suggest that, in general, any true bifurcation of a nonlinear dynamical system can be unequivocally uncovered through adiabatic parameter sweeping, in spite of a shift in the bifurcation point, which is of value to experimental studies of nonlinear dynamical systems.
AU - Park, Youngyong
AU - Do, Younghae
AU - Altmeyer, Sebastian
AU - Lai, Yingcheng
AU - Lee, Gyuwon
ID - 1868
IS - 2
JF - Physical Review E
SN - 1539-3755
TI - Early effect in time-dependent, high-dimensional nonlinear dynamical systems with multiple resonances
VL - 91
ER -
TY - JOUR
AB - The plant hormone auxin is a key regulator of plant growth and development. Differences in auxin distribution within tissues are mediated by the polar auxin transport machinery, and cellular auxin responses occur depending on changes in cellular auxin levels. Multiple receptor systems at the cell surface and in the interior operate to sense and interpret fluctuations in auxin distribution that occur during plant development. Until now, three proteins or protein complexes that can bind auxin have been identified. SCFTIR1 [a SKP1-cullin-1-F-box complex that contains transport inhibitor response 1 (TIR1) as the F-box protein] and S-phase-kinaseassociated protein 2 (SKP2) localize to the nucleus, whereas auxinbinding protein 1 (ABP1), predominantly associates with the endoplasmic reticulum and cell surface. In this Cell Science at a Glance article, we summarize recent discoveries in the field of auxin transport and signaling that have led to the identification of new components of these pathways, as well as their mutual interaction.
AU - Grones, Peter
AU - Friml, Jirí
ID - 1871
IS - 1
JF - Journal of Cell Science
TI - Auxin transporters and binding proteins at a glance
VL - 128
ER -
TY - JOUR
AB - We consider partially observable Markov decision processes (POMDPs) with limit-average payoff, where a reward value in the interval [0,1] is associated with every transition, and the payoff of an infinite path is the long-run average of the rewards. We consider two types of path constraints: (i) a quantitative constraint defines the set of paths where the payoff is at least a given threshold λ1ε(0,1]; and (ii) a qualitative constraint which is a special case of the quantitative constraint with λ1=1. We consider the computation of the almost-sure winning set, where the controller needs to ensure that the path constraint is satisfied with probability 1. Our main results for qualitative path constraints are as follows: (i) the problem of deciding the existence of a finite-memory controller is EXPTIME-complete; and (ii) the problem of deciding the existence of an infinite-memory controller is undecidable. For quantitative path constraints we show that the problem of deciding the existence of a finite-memory controller is undecidable. We also present a prototype implementation of our EXPTIME algorithm and experimental results on several examples.
AU - Chatterjee, Krishnendu
AU - Chmelik, Martin
ID - 1873
JF - Artificial Intelligence
TI - POMDPs under probabilistic semantics
VL - 221
ER -
TY - JOUR
AB - The hippocampal region, comprising the hippocampal formation and the parahippocampal region, has been one of the most intensively studied parts of the brain for decades. Better understanding of its functional diversity and complexity has led to an increased demand for specificity in experimental procedures and manipulations. In view of the complex 3D structure of the hippocampal region, precisely positioned experimental approaches require a fine-grained architectural description that is available and readable to experimentalists lacking detailed anatomical experience. In this paper, we provide the first cyto- and chemoarchitectural description of the hippocampal formation and parahippocampal region in the rat at high resolution and in the three standard sectional planes: coronal, horizontal and sagittal. The atlas uses a series of adjacent sections stained for neurons and for a number of chemical marker substances, particularly parvalbumin and calbindin. All the borders defined in one plane have been cross-checked against their counterparts in the other two planes. The entire dataset will be made available as a web-based interactive application through the Rodent Brain WorkBench (http://www.rbwb.org) which, together with this paper, provides a unique atlas resource.
AU - Boccara, Charlotte
AU - Kjønigsen, Lisa
AU - Hammer, Ingvild
AU - Bjaalie, Jan
AU - Leergaard, Trygve
AU - Witter, Menno
ID - 1874
IS - 7
JF - Hippocampus
TI - A three-plane architectonic atlas of the rat hippocampal region
VL - 25
ER -
TY - JOUR
AB - Petrocoptis is a small genus of chasmophytic plants endemic to the Iberian Peninsula, with some localized populations in the French Pyrenees. Within the genus, a dozen species have been recognized based on morphological diversity, most of them with limited distribution area, in small populations and frequently with potential threats to their survival. To date, however, a molecular evaluation of the current systematic treatments has not been carried out. The aim of the present study is to infer phylogenetic relationships among its subordinate taxa by using plastidial rps16 intron and nuclear internal transcribed spacer (ITS) DNA sequences; and evaluate the phylogenetic placement of the genus Petrocoptis within the family Caryophyllaceae. The monophyly of Petrocoptis is supported by both ITS and rps16 intron sequence analyses. Furthermore, time estimates using BEAST analyses indicate a Middle to Late Miocene diversification (10.59 Myr, 6.44–15.26 Myr highest posterior densities [HPD], for ITS; 14.30 Myr, 8.61–21.00 Myr HPD, for rps16 intron).
AU - Cires Rodriguez, Eduardo
AU - Prieto, José
ID - 1878
IS - 2
JF - Journal of Plant Research
TI - Phylogenetic relationships of Petrocoptis A. Braun ex Endl. (Caryophyllaceae), a discussed genus from the Iberian Peninsula
VL - 128
ER -
TY - JOUR
AB - When electron microscopy (EM) was introduced in the 1930s it gave scientists their first look into the nanoworld of cells. Over the last 80 years EM has vastly increased our understanding of the complex cellular structures that underlie the diverse functions that cells need to maintain life. One drawback that has been difficult to overcome was the inherent lack of volume information, mainly due to the limit on the thickness of sections that could be viewed in a transmission electron microscope (TEM). For many years scientists struggled to achieve three-dimensional (3D) EM using serial section reconstructions, TEM tomography, and scanning EM (SEM) techniques such as freeze-fracture. Although each technique yielded some special information, they required a significant amount of time and specialist expertise to obtain even a very small 3D EM dataset. Almost 20 years ago scientists began to exploit SEMs to image blocks of embedded tissues and perform serial sectioning of these tissues inside the SEM chamber. Using first focused ion beams (FIB) and subsequently robotic ultramicrotomes (serial block-face, SBF-SEM) microscopists were able to collect large volumes of 3D EM information at resolutions that could address many important biological questions, and do so in an efficient manner. We present here some examples of 3D EM taken from the many diverse specimens that have been imaged in our core facility. We propose that the next major step forward will be to efficiently correlate functional information obtained using light microscopy (LM) with 3D EM datasets to more completely investigate the important links between cell structures and their functions.
AU - Kremer, A
AU - Lippens, Stefaan
AU - Bartunkova, Sonia
AU - Asselbergh, Bob
AU - Blanpain, Cendric
AU - Fendrych, Matyas
AU - Goossens, A
AU - Holt, Matthew
AU - Janssens, Sophie
AU - Krols, Michiel
AU - Larsimont, Jean
AU - Mc Guire, Conor
AU - Nowack, Moritz
AU - Saelens, Xavier
AU - Schertel, Andreas
AU - Schepens, B
AU - Slezak, M
AU - Timmerman, Vincent
AU - Theunis, Clara
AU - Van Brempt, Ronald
AU - Visser, Y
AU - Guérin, Christophe
ID - 1879
IS - 2
JF - Journal of Microscopy
TI - Developing 3D SEM in a broad biological context
VL - 259
ER -
TY - JOUR
AB - We investigate the relation between Bose-Einstein condensation (BEC) and superfluidity in the ground state of a one-dimensional model of interacting bosons in a strong random potential. We prove rigorously that in a certain parameter regime the superfluid fraction can be arbitrarily small while complete BEC prevails. In another regime there is both complete BEC and complete superfluidity, despite the strong disorder
AU - Könenberg, Martin
AU - Moser, Thomas
AU - Seiringer, Robert
AU - Yngvason, Jakob
ID - 1880
JF - New Journal of Physics
TI - Superfluid behavior of a Bose-Einstein condensate in a random potential
VL - 17
ER -
TY - CONF
AB - We provide a framework for compositional and iterative design and verification of systems with quantitative information, such as rewards, time or energy. It is based on disjunctive modal transition systems where we allow actions to bear various types of quantitative information. Throughout the design process the actions can be further refined and the information made more precise. We show how to compute the results of standard operations on the systems, including the quotient (residual), which has not been previously considered for quantitative non-deterministic systems. Our quantitative framework has close connections to the modal nu-calculus and is compositional with respect to general notions of distances between systems and the standard operations.
AU - Fahrenberg, Uli
AU - Kretinsky, Jan
AU - Legay, Axel
AU - Traonouez, Louis
ID - 1882
TI - Compositionality for quantitative specifications
VL - 8997
ER -
TY - JOUR
AB - We introduce a one-parametric family of tree growth models, in which branching probabilities decrease with branch age τ as τ-α. Depending on the exponent α, the scaling of tree depth with tree size n displays a transition between the logarithmic scaling of random trees and an algebraic growth. At the transition (α=1) tree depth grows as (logn)2. This anomalous scaling is in good agreement with the trend observed in evolution of biological species, thus providing a theoretical support for age-dependent speciation and associating it to the occurrence of a critical point.
AU - Keller-Schmidt, Stephanie
AU - Tugrul, Murat
AU - Eguíluz, Víctor
AU - Hernandez Garcia, Emilio
AU - Klemm, Konstantin
ID - 1883
IS - 2
JF - Physical Review E Statistical Nonlinear and Soft Matter Physics
TI - Anomalous scaling in an age-dependent branching model
VL - 91
ER -
TY - JOUR
AB - The concept of positional information is central to our understanding of how cells determine their location in a multicellular structure and thereby their developmental fates. Nevertheless, positional information has neither been defined mathematically nor quantified in a principled way. Here we provide an information-theoretic definition in the context of developmental gene expression patterns and examine the features of expression patterns that affect positional information quantitatively. We connect positional information with the concept of positional error and develop tools to directly measure information and error from experimental data. We illustrate our framework for the case of gap gene expression patterns in the early Drosophila embryo and show how information that is distributed among only four genes is sufficient to determine developmental fates with nearly single-cell resolution. Our approach can be generalized to a variety of different model systems; procedures and examples are discussed in detail.
AU - Tkacik, Gasper
AU - Dubuis, Julien
AU - Petkova, Mariela
AU - Gregor, Thomas
ID - 1885
IS - 1
JF - Genetics
TI - Positional information, positional error, and readout precision in morphogenesis: A mathematical framework
VL - 199
ER -
TY - JOUR
AB - We numerically investigate the distribution of extrema of 'chaotic' Laplacian eigenfunctions on two-dimensional manifolds. Our contribution is two-fold: (a) we count extrema on grid graphs with a small number of randomly added edges and show the behavior to coincide with the 1957 prediction of Longuet-Higgins for the continuous case and (b) we compute the regularity of their spatial distribution using discrepancy, which is a classical measure from the theory of Monte Carlo integration. The first part suggests that grid graphs with randomly added edges should behave like two-dimensional surfaces with ergodic geodesic flow; in the second part we show that the extrema are more regularly distributed in space than the grid Z2.
AU - Pausinger, Florian
AU - Steinerberger, Stefan
ID - 1938
IS - 6
JF - Physics Letters, Section A
TI - On the distribution of local extrema in quantum chaos
VL - 379
ER -
TY - JOUR
AU - Dereziński, Jan
AU - Napiórkowski, Marcin M
ID - 1939
IS - 7
JF - Annales Henri Poincare
TI - Erratum to: Excitation spectrum of interacting bosons in the Mean-Field Infinite-Volume limit
VL - 16
ER -
TY - JOUR
AB - We typically think of cells as responding to external signals independently by regulating their gene expression levels, yet they often locally exchange information and coordinate. Can such spatial coupling be of benefit for conveying signals subject to gene regulatory noise? Here we extend our information-theoretic framework for gene regulation to spatially extended systems. As an example, we consider a lattice of nuclei responding to a concentration field of a transcriptional regulator (the "input") by expressing a single diffusible target gene. When input concentrations are low, diffusive coupling markedly improves information transmission; optimal gene activation functions also systematically change. A qualitatively new regulatory strategy emerges where individual cells respond to the input in a nearly step-like fashion that is subsequently averaged out by strong diffusion. While motivated by early patterning events in the Drosophila embryo, our framework is generically applicable to spatially coupled stochastic gene expression models.
AU - Sokolowski, Thomas R
AU - Tkacik, Gasper
ID - 1940
IS - 6
JF - Physical Review E Statistical Nonlinear and Soft Matter Physics
TI - Optimizing information flow in small genetic networks. IV. Spatial coupling
VL - 91
ER -
TY - JOUR
AU - Rakusová, Hana
AU - Fendrych, Matyas
AU - Friml, Jirí
ID - 1944
IS - 2
JF - Current Opinion in Plant Biology
TI - Intracellular trafficking and PIN-mediated cell polarity during tropic responses in plants
VL - 23
ER -
TY - CONF
AB - We present a method and a tool for generating succinct representations of sets of concurrent traces. We focus on trace sets that contain all correct or all incorrect permutations of events from a given trace. We represent trace sets as HB-Formulas that are Boolean combinations of happens-before constraints between events. To generate a representation of incorrect interleavings, our method iteratively explores interleavings that violate the specification and gathers generalizations of the discovered interleavings into an HB-Formula; its complement yields a representation of correct interleavings.
We claim that our trace set representations can drive diverse verification, fault localization, repair, and synthesis techniques for concurrent programs. We demonstrate this by using our tool in three case studies involving synchronization synthesis, bug summarization, and abstraction refinement based verification. In each case study, our initial experimental results have been promising.
In the first case study, we present an algorithm for inferring missing synchronization from an HB-Formula representing correct interleavings of a given trace. The algorithm applies rules to rewrite specific patterns in the HB-Formula into locks, barriers, and wait-notify constructs. In the second case study, we use an HB-Formula representing incorrect interleavings for bug summarization. While the HB-Formula itself is a concise counterexample summary, we present additional inference rules to help identify specific concurrency bugs such as data races, define-use order violations, and two-stage access bugs. In the final case study, we present a novel predicate learning procedure that uses HB-Formulas representing abstract counterexamples to accelerate counterexample-guided abstraction refinement (CEGAR). In each iteration of the CEGAR loop, the procedure refines the abstraction to eliminate multiple spurious abstract counterexamples drawn from the HB-Formula.
AU - Gupta, Ashutosh
AU - Henzinger, Thomas A
AU - Radhakrishna, Arjun
AU - Samanta, Roopsha
AU - Tarrach, Thorsten
ID - 1992
SN - 978-1-4503-3300-9
TI - Succinct representation of concurrent trace sets
ER -
TY - JOUR
AB - The fitness effects of symbionts on their hosts can be context-dependent, with usually benign symbionts causing detrimental effects when their hosts are stressed, or typically parasitic symbionts providing protection towards their hosts (e.g. against pathogen infection). Here, we studied the novel association between the invasive garden ant Lasius neglectus and its fungal ectosymbiont Laboulbenia formicarum for potential costs and benefits. We tested ants with different Laboulbenia levels for their survival and immunity under resource limitation and exposure to the obligate killing entomopathogen Metarhizium brunneum. While survival of L. neglectus workers under starvation was significantly decreased with increasing Laboulbenia levels, host survival under Metarhizium exposure increased with higher levels of the ectosymbiont, suggesting a symbiont-mediated anti-pathogen protection, which seems to be driven mechanistically by both improved sanitary behaviours and an upregulated immune system. Ants with high Laboulbenia levels showed significantly longer self-grooming and elevated expression of immune genes relevant for wound repair and antifungal responses (β-1,3-glucan binding protein, Prophenoloxidase), compared with ants carrying low Laboulbenia levels. This suggests that the ectosymbiont Laboulbenia formicarum weakens its ant host by either direct resource exploitation or the costs of an upregulated behavioural and immunological response, which, however, provides a prophylactic protection upon later exposure to pathogens.
AU - Konrad, Matthias
AU - Grasse, Anna V
AU - Tragust, Simon
AU - Cremer, Sylvia
ID - 1993
IS - 1799
JF - Proceedings of the Royal Society of London Series B Biological Sciences
TI - Anti-pathogen protection versus survival costs mediated by an ectosymbiont in an ant host
VL - 282
ER -
TY - JOUR
AB - We prove that the three-state toric homogeneous Markov chain model has Markov degree two. In algebraic terminology this means, that a certain class of toric ideals is generated by quadratic binomials. This was conjectured by Haws, Martin del Campo, Takemura and Yoshida, who proved that they are generated by degree six binomials.
AU - Noren, Patrik
ID - 1997
IS - May-June
JF - Journal of Symbolic Computation
TI - The three-state toric homogeneous Markov chain model has Markov degree two
VL - 68/Part 2
ER -
TY - JOUR
AB - The monotone secant conjecture posits a rich class of polynomial systems, all of whose solutions are real. These systems come from the Schubert calculus on flag manifolds, and the monotone secant conjecture is a compelling generalization of the Shapiro conjecture for Grassmannians (Theorem of Mukhin, Tarasov, and Varchenko). We present some theoretical evidence for this conjecture, as well as computational evidence obtained by 1.9 teraHertz-years of computing, and we discuss some of the phenomena we observed in our data.
AU - Hein, Nicolas
AU - Hillar, Christopher
AU - Martin Del Campo Sanchez, Abraham
AU - Sottile, Frank
AU - Teitler, Zach
ID - 2006
IS - 3
JF - Experimental Mathematics
TI - The monotone secant conjecture in the real Schubert calculus
VL - 24
ER -
TY - JOUR
AB - The paper describes a generalized iterative proportional fitting procedure that can be used for maximum likelihood estimation in a special class of the general log-linear model. The models in this class, called relational, apply to multivariate discrete sample spaces that do not necessarily have a Cartesian product structure and may not contain an overall effect. When applied to the cell probabilities, the models without the overall effect are curved exponential families and the values of the sufficient statistics are reproduced by the MLE only up to a constant of proportionality. The paper shows that Iterative Proportional Fitting, Generalized Iterative Scaling, and Improved Iterative Scaling fail to work for such models. The algorithm proposed here is based on iterated Bregman projections. As a by-product, estimates of the multiplicative parameters are also obtained. An implementation of the algorithm is available as an R-package.
AU - Klimova, Anna
AU - Rudas, Tamás
ID - 2008
IS - 3
JF - Scandinavian Journal of Statistics
TI - Iterative scaling in curved exponential families
VL - 42
ER -
TY - JOUR
AB - The concepts of faithfulness and strong-faithfulness are important for statistical learning of graphical models. Graphs are not sufficient for describing the association structure of a discrete distribution. Hypergraphs representing hierarchical log-linear models are considered instead, and the concept of parametric (strong-) faithfulness with respect to a hypergraph is introduced. Strong-faithfulness ensures the existence of uniformly consistent parameter estimators and enables building uniformly consistent procedures for a hypergraph search. The strength of association in a discrete distribution can be quantified with various measures, leading to different concepts of strong-faithfulness. Lower and upper bounds for the proportions of distributions that do not satisfy strong-faithfulness are computed for different parameterizations and measures of association.
AU - Klimova, Anna
AU - Uhler, Caroline
AU - Rudas, Tamás
ID - 2014
IS - 7
JF - Computational Statistics & Data Analysis
TI - Faithfulness and learning hypergraphs from discrete distributions
VL - 87
ER -
TY - JOUR
AB - Small GTP-binding proteins of the Ras superfamily play diverse roles in intracellular trafficking. Among them, the Rab, Arf, and Rho families function in successive steps of vesicle transport, in forming vesicles from donor membranes, directing vesicle trafficking toward target membranes and docking vesicles onto target membranes. These proteins act as molecular switches that are controlled by a cycle of GTP binding and hydrolysis regulated by guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs). In this study we explored the role of GAPs in the regulation of the endocytic pathway using fluorescently labeled yeast mating pheromone α-factor. Among 25 non-essential GAP mutants, we found that deletion of the GLO3 gene, encoding Arf-GAP protein, caused defective internalization of fluorescently labeled α-factor. Quantitative analysis revealed that glo3Δ cells show defective α-factor binding to the cell surface. Interestingly, Ste2p, the α-factor receptor, was mis-localized from the plasma membrane to the vacuole in glo3Δ cells. Domain deletion mutants of Glo3p revealed that a GAP-independent function, as well as the GAP activity, of Glo3p is important for both α-factor binding and Ste2p localization at the cell surface. Additionally, we found that deletion of the GLO3 gene affects the size and number of Arf1p-residing Golgi compartments and causes a defect in transport from the TGN to the plasma membrane. Furthermore, we demonstrated that glo3Δ cells were defective in the late endosome-to-TGN transport pathway, but not in the early endosome-to-TGN transport pathway. These findings suggest novel roles for Arf-GAP Glo3p in endocytic recycling of cell surface proteins.
AU - Kawada, Daiki
AU - Kobayashi, Hiromu
AU - Tomita, Tsuyoshi
AU - Nakata, Eisuke
AU - Nagano, Makoto
AU - Siekhaus, Daria E
AU - Toshima, Junko
AU - Toshimaa, Jiro
ID - 2025
IS - 1
JF - Biochimica et Biophysica Acta - Molecular Cell Research
TI - The yeast Arf-GAP Glo3p is required for the endocytic recycling of cell surface proteins
VL - 1853
ER -
TY - JOUR
AB - A hybrid-parallel direct-numerical-simulation method with application to turbulent Taylor-Couette flow is presented. The Navier-Stokes equations are discretized in cylindrical coordinates with the spectral Fourier-Galerkin method in the axial and azimuthal directions, and high-order finite differences in the radial direction. Time is advanced by a second-order, semi-implicit projection scheme, which requires the solution of five Helmholtz/Poisson equations, avoids staggered grids and renders very small slip velocities. Nonlinear terms are evaluated with the pseudospectral method. The code is parallelized using a hybrid MPI-OpenMP strategy, which, compared with a flat MPI parallelization, is simpler to implement, allows to reduce inter-node communications and MPI overhead that become relevant at high processor-core counts, and helps to contain the memory footprint. A strong scaling study shows that the hybrid code maintains scalability up to more than 20,000 processor cores and thus allows to perform simulations at higher resolutions than previously feasible. In particular, it opens up the possibility to simulate turbulent Taylor-Couette flows at Reynolds numbers up to O(105). This enables to probe hydrodynamic turbulence in Keplerian flows in experimentally relevant regimes.
AU - Shi, Liang
AU - Rampp, Markus
AU - Hof, Björn
AU - Avila, Marc
ID - 2030
IS - 1
JF - Computers and Fluids
TI - A hybrid MPI-OpenMP parallel implementation for pseudospectral simulations with application to Taylor-Couette flow
VL - 106
ER -
TY - JOUR
AB - Opacity is a generic security property, that has been defined on (non-probabilistic) transition systems and later on Markov chains with labels. For a secret predicate, given as a subset of runs, and a function describing the view of an external observer, the value of interest for opacity is a measure of the set of runs disclosing the secret. We extend this definition to the richer framework of Markov decision processes, where non-deterministicchoice is combined with probabilistic transitions, and we study related decidability problems with partial or complete observation hypotheses for the schedulers. We prove that all questions are decidable with complete observation and ω-regular secrets. With partial observation, we prove that all quantitative questions are undecidable but the question whether a system is almost surely non-opaquebecomes decidable for a restricted class of ω-regular secrets, as well as for all ω-regular secrets under finite-memory schedulers.
AU - Bérard, Béatrice
AU - Chatterjee, Krishnendu
AU - Sznajder, Nathalie
ID - 2034
IS - 1
JF - Information Processing Letters
TI - Probabilistic opacity for Markov decision processes
VL - 115
ER -
TY - JOUR
AB - Considering a continuous self-map and the induced endomorphism on homology, we study the eigenvalues and eigenspaces of the latter. Taking a filtration of representations, we define the persistence of the eigenspaces, effectively introducing a hierarchical organization of the map. The algorithm that computes this information for a finite sample is proved to be stable, and to give the correct answer for a sufficiently dense sample. Results computed with an implementation of the algorithm provide evidence of its practical utility.
AU - Edelsbrunner, Herbert
AU - Jablonski, Grzegorz
AU - Mrozek, Marian
ID - 2035
IS - 5
JF - Foundations of Computational Mathematics
TI - The persistent homology of a self-map
VL - 15
ER -
TY - JOUR
AB - We study the spectrum of a large system of N identical bosons interacting via a two-body potential with strength 1/N. In this mean-field regime, Bogoliubov's theory predicts that the spectrum of the N-particle Hamiltonian can be approximated by that of an effective quadratic Hamiltonian acting on Fock space, which describes the fluctuations around a condensed state. Recently, Bogoliubov's theory has been justified rigorously in the case that the low-energy eigenvectors of the N-particle Hamiltonian display complete condensation in the unique minimizer of the corresponding Hartree functional. In this paper, we shall justify Bogoliubov's theory for the high-energy part of the spectrum of the N-particle Hamiltonian corresponding to (non-linear) excited states of the Hartree functional. Moreover, we shall extend the existing results on the excitation spectrum to the case of non-uniqueness and/or degeneracy of the Hartree minimizer. In particular, the latter covers the case of rotating Bose gases, when the rotation speed is large enough to break the symmetry and to produce multiple quantized vortices in the Hartree minimizer.
AU - Nam, Phan
AU - Seiringer, Robert
ID - 2085
IS - 2
JF - Archive for Rational Mechanics and Analysis
TI - Collective excitations of Bose gases in the mean-field regime
VL - 215
ER -
TY - JOUR
AB - We consider the spectral statistics of large random band matrices on mesoscopic energy scales. We show that the correlation function of the local eigenvalue density exhibits a universal power law behaviour that differs from the Wigner-Dyson- Mehta statistics. This law had been predicted in the physics literature by Altshuler and Shklovskii in (Zh Eksp Teor Fiz (Sov Phys JETP) 91(64):220(127), 1986); it describes the correlations of the eigenvalue density in general metallic sampleswith weak disorder. Our result rigorously establishes the Altshuler-Shklovskii formulas for band matrices. In two dimensions, where the leading term vanishes owing to an algebraic cancellation, we identify the first non-vanishing term and show that it differs substantially from the prediction of Kravtsov and Lerner in (Phys Rev Lett 74:2563-2566, 1995). The proof is given in the current paper and its companion (Ann. H. Poincaré. arXiv:1309.5107, 2014).
AU - Erdös, László
AU - Knowles, Antti
ID - 2166
IS - 3
JF - Communications in Mathematical Physics
TI - The Altshuler-Shklovskii formulas for random band matrices I: the unimodular case
VL - 333
ER -
TY - JOUR
AB - The rational design of monodisperse ferroelectric nanocrystals with controlled size and shape and their organization into hierarchical structures has been a critical step for understanding the polar ordering in nanoscale ferroelectrics, as well as the design of nanocrystal-based functional materials which harness the properties of individual nanoparticles and the collective interactions between them. We report here on the synthesis and self-assembly of aggregate-free, single-crystalline titanium-based perovskite nanoparticles with controlled morphology and surface composition by using a simple, easily scalable and highly versatile colloidal route. Single-crystalline, non-aggregated BaTiO3 colloidal nanocrystals, used as a model system, have been prepared under solvothermal conditions at temperatures as low as 180 °C. The shape of the nanocrystals was tuned from spheroidal to cubic upon changing the polarity of the solvent, whereas their size was varied from 16 to 30 nm for spheres and 5 to 78 nm for cubes by changing the concentration of the precursors and the reaction time, respectively. The hydrophobic, oleic acid-passivated nanoparticles exhibit very good solubility in non-polar solvents and can be rendered dispersible in polar solvents by a simple process involving the oxidative cleavage of the double bond upon treating the nanopowders with the Lemieux–von Rudloff reagent. Lattice dynamic analysis indicated that regardless of their size, BaTiO3 nanocrystals present local disorder within the perovskite unit cell, associated with the existence of polar ordering. We also demonstrate for the first time that, in addition to being used for fabricating large area, crack-free, highly uniform films, BaTiO3 nanocubes can serve as building blocks for the design of 2D and 3D mesoscale structures, such as superlattices and superparticles. Interestingly, the type of superlattice structure (simple cubic or face centered cubic) appears to be determined by the type of solvent in which the nanocrystals were dispersed. This approach provides an excellent platform for the synthesis of other titanium-based perovskite colloidal nanocrystals with controlled chemical composition, surface structure and morphology and for their assembly into complex architectures, therefore opening the door for the design of novel mesoscale functional materials/nanocomposites with potential applications in energy conversion, data storage and the biomedical field.
AU - Caruntu, Daniela
AU - Rostamzadeh, Taha
AU - Costanzo, Tommaso
AU - Salemizadeh Parizi, Saman
AU - Caruntu, Gabriel
ID - 7456
IS - 30
JF - Nanoscale
SN - 2040-3364
TI - Solvothermal synthesis and controlled self-assembly of monodisperse titanium-based perovskite colloidal nanocrystals
VL - 7
ER -
TY - JOUR
AB - A new organic–inorganic ferroelectric hybrid capacitor designed by uniformly incorporating surface modified monodisperse 15 nm ferroelectric BaTiO3 nanocubes into non-polar polymer blends of poly(methyl methacrylate) (PMMA) polymer and acrylonitrile-butadiene-styrene (ABS) terpolymer is described. The investigation of spatial distribution of nanofillers via a non-distractive thermal pulse method illustrates that the surface functionalization of nanocubes plays a key role in the uniform distribution of charge polarization within the polymer matrix. The discharged energy density of the nanocomposite with 30 vol% BaTiO3 nanocubes is ∼44 × 10−3 J cm−3, which is almost six times higher than that of the neat polymer. The facile processing, along with the superior mechanical and electrical properties of the BaTiO3/PMMA–ABS nanocomposites make them suitable for implementation into capacitive electrical energy storage devices.
AU - Parizi, Saman Salemizadeh
AU - Conley, Gavin
AU - Costanzo, Tommaso
AU - Howell, Bob
AU - Mellinger, Axel
AU - Caruntu, Gabriel
ID - 7457
IS - 93
JF - RSC Advances
SN - 2046-2069
TI - Fabrication of barium titanate/acrylonitrile-butadiene styrene/poly(methyl methacrylate) nanocomposite films for hybrid ferroelectric capacitors
VL - 5
ER -
TY - JOUR
AB - Currently, there is much debate on the genetic architecture of quantitative traits in wild populations. Is trait variation influenced by many genes of small effect or by a few genes of major effect? Where is additive genetic variation located in the genome? Do the same loci cause similar phenotypic variation in different populations? Great tits (Parus major) have been studied extensively in long‐term studies across Europe and consequently are considered an ecological ‘model organism’. Recently, genomic resources have been developed for the great tit, including a custom SNP chip and genetic linkage map. In this study, we used a suite of approaches to investigate the genetic architecture of eight quantitative traits in two long‐term study populations of great tits—one in the Netherlands and the other in the United Kingdom. Overall, we found little evidence for the presence of genes of large effects in either population. Instead, traits appeared to be influenced by many genes of small effect, with conservative estimates of the number of contributing loci ranging from 31 to 310. Despite concordance between population‐specific heritabilities, we found no evidence for the presence of loci having similar effects in both populations. While population‐specific genetic architectures are possible, an undetected shared architecture cannot be rejected because of limited power to map loci of small and moderate effects. This study is one of few examples of genetic architecture analysis in replicated wild populations and highlights some of the challenges and limitations researchers will face when attempting similar molecular quantitative genetic studies in free‐living populations.
AU - Santure, Anna W.
AU - Poissant, Jocelyn
AU - De Cauwer, Isabelle
AU - van Oers, Kees
AU - Robinson, Matthew Richard
AU - Quinn, John L.
AU - Groenen, Martien A. M.
AU - Visser, Marcel E.
AU - Sheldon, Ben C.
AU - Slate, Jon
ID - 7739
JF - Molecular Ecology
SN - 0962-1083
TI - Replicated analysis of the genetic architecture of quantitative traits in two wild great tit populations
VL - 24
ER -
TY - JOUR
AB - Phenotypes expressed in a social context are not only a function of the individual, but can also be shaped by the phenotypes of social partners. These social effects may play a major role in the evolution of cooperative breeding if social partners differ in the quality of care they provide and if individual carers adjust their effort in relation to that of other carers. When applying social effects models to wild study systems, it is also important to explore sources of individual plasticity that could masquerade as social effects. We studied offspring provisioning rates of parents and helpers in a wild population of long-tailed tits Aegithalos caudatus using a quantitative genetic framework to identify these social effects and partition them into genetic, permanent environment and current environment components. Controlling for other effects, individuals were consistent in their provisioning effort at a given nest, but adjusted their effort based on who was in their social group, indicating the presence of social effects. However, these social effects differed between years and social contexts, indicating a current environment effect, rather than indicating a genetic or permanent environment effect. While this study reveals the importance of examining environmental and genetic sources of social effects, the framework we present is entirely general, enabling a greater understanding of potentially important social effects within any ecological population.
AU - Adams, Mark James
AU - Robinson, Matthew Richard
AU - Mannarelli, Maria-Elena
AU - Hatchwell, Ben J.
ID - 7741
IS - 1810
JF - Proceedings of the Royal Society B: Biological Sciences
SN - 0962-8452
TI - Social genetic and social environment effects on parental and helper care in a cooperatively breeding bird
VL - 282
ER -
TY - JOUR
AB - Across-nation differences in the mean values for complex traits are common1,2,3,4,5,6,7,8, but the reasons for these differences are unknown. Here we find that many independent loci contribute to population genetic differences in height and body mass index (BMI) in 9,416 individuals across 14 European countries. Using discovery data on over 250,000 individuals and unbiased effect size estimates from 17,500 sibling pairs, we estimate that 24% (95% credible interval (CI) = 9%, 41%) and 8% (95% CI = 4%, 16%) of the captured additive genetic variance for height and BMI, respectively, reflect population genetic differences. Population genetic divergence differed significantly from that in a null model (height, P < 3.94 × 10−8; BMI, P < 5.95 × 10−4), and we find an among-population genetic correlation for tall and slender individuals (r = −0.80, 95% CI = −0.95, −0.60), consistent with correlated selection for both phenotypes. Observed differences in height among populations reflected the predicted genetic means (r = 0.51; P < 0.001), but environmental differences across Europe masked genetic differentiation for BMI (P < 0.58).
AU - Robinson, Matthew Richard
AU - Hemani, Gibran
AU - Medina-Gomez, Carolina
AU - Mezzavilla, Massimo
AU - Esko, Tonu
AU - Shakhbazov, Konstantin
AU - Powell, Joseph E
AU - Vinkhuyzen, Anna
AU - Berndt, Sonja I
AU - Gustafsson, Stefan
AU - Justice, Anne E
AU - Kahali, Bratati
AU - Locke, Adam E
AU - Pers, Tune H
AU - Vedantam, Sailaja
AU - Wood, Andrew R
AU - van Rheenen, Wouter
AU - Andreassen, Ole A
AU - Gasparini, Paolo
AU - Metspalu, Andres
AU - Berg, Leonard H van den
AU - Veldink, Jan H
AU - Rivadeneira, Fernando
AU - Werge, Thomas M
AU - Abecasis, Goncalo R
AU - Boomsma, Dorret I
AU - Chasman, Daniel I
AU - de Geus, Eco J C
AU - Frayling, Timothy M
AU - Hirschhorn, Joel N
AU - Hottenga, Jouke Jan
AU - Ingelsson, Erik
AU - Loos, Ruth J F
AU - Magnusson, Patrik K E
AU - Martin, Nicholas G
AU - Montgomery, Grant W
AU - North, Kari E
AU - Pedersen, Nancy L
AU - Spector, Timothy D
AU - Speliotes, Elizabeth K
AU - Goddard, Michael E
AU - Yang, Jian
AU - Visscher, Peter M
ID - 7742
IS - 11
JF - Nature Genetics
SN - 1061-4036
TI - Population genetic differentiation of height and body mass index across Europe
VL - 47
ER -
TY - CONF
AB - High-performance concurrent priority queues are essential for applications such as task scheduling and discrete event simulation. Unfortunately, even the best performing implementations do not scale past a number of threads in the single digits. This is because of the sequential bottleneck in accessing the elements at the head of the queue in order to perform a DeleteMin operation. In this paper, we present the SprayList, a scalable priority queue with relaxed ordering semantics. Starting from a non-blocking SkipList, the main innovation behind our design is that the DeleteMin operations avoid a sequential bottleneck by "spraying" themselves onto the head of the SkipList list in a coordinated fashion. The spraying is implemented using a carefully designed random walk, so that DeleteMin returns an element among the first O(plog3p) in the list, with high probability, where p is the number of threads. We prove that the running time of a DeleteMin operation is O(log3p), with high probability, independent of the size of the list. Our experiments show that the relaxed semantics allow the data structure to scale for high thread counts, comparable to a classic unordered SkipList. Furthermore, we observe that, for reasonably parallel workloads, the scalability benefits of relaxation considerably outweigh the additional work due to out-of-order execution.
AU - Alistarh, Dan-Adrian
AU - Kopinsky, Justin
AU - Li, Jerry
AU - Shavit, Nir
ID - 776
TI - The SprayList: A scalable relaxed priority queue
VL - 2015-January
ER -
TY - JOUR
AB - We introduce a principle unique to disordered solids wherein the contribution of any bond to one global perturbation is uncorrelated with its contribution to another. Coupled with sufficient variability in the contributions of different bonds, this “independent bond-level response” paves the way for the design of real materials with unusual and exquisitely tuned properties. To illustrate this, we choose two global perturbations: compression and shear. By applying a bond removal procedure that is both simple and experimentally relevant to remove a very small fraction of bonds, we can drive disordered spring networks to both the incompressible and completely auxetic limits of mechanical behavior.
AU - Goodrich, Carl Peter
AU - Liu, Andrea J.
AU - Nagel, Sidney R.
ID - 7765
IS - 22
JF - Physical Review Letters
SN - 0031-9007
TI - The principle of independent bond-level response: Tuning by pruning to exploit disorder for global behavior
VL - 114
ER -
TY - JOUR
AB - We study the vibrational properties near a free surface of disordered spring networks derived from jammed sphere packings. In bulk systems, without surfaces, it is well understood that such systems have a plateau in the density of vibrational modes extending down to a frequency scale ω*. This frequency is controlled by ΔZ = 〈Z〉 − 2d, the difference between the average coordination of the spheres and twice the spatial dimension, d, of the system, which vanishes at the jamming transition. In the presence of a free surface we find that there is a density of disordered vibrational modes associated with the surface that extends far below ω*. The total number of these low-frequency surface modes is controlled by ΔZ, and the profile of their decay into the bulk has two characteristic length scales, which diverge as ΔZ−1/2 and ΔZ−1 as the jamming transition is approached.
AU - Sussman, Daniel M.
AU - Goodrich, Carl Peter
AU - Liu, Andrea J.
AU - Nagel, Sidney R.
ID - 7766
IS - 14
JF - Soft Matter
SN - 1744-683X
TI - Disordered surface vibrations in jammed sphere packings
VL - 11
ER -
TY - JOUR
AB - We present a model of soft active particles that leads to a rich array of collective behavior found also in dense biological swarms of bacteria and other unicellular organisms. Our model uses only local interactions, such as Vicsek-type nearest-neighbor alignment, short-range repulsion, and a local boundary term. Changing the relative strength of these interactions leads to migrating swarms, rotating swarms, and jammed swarms, as well as swarms that exhibit run-and-tumble motion, alternating between migration and either rotating or jammed states. Interestingly, although a migrating swarm moves slower than an individual particle, the diffusion constant can be up to three orders of magnitude larger, suggesting that collective motion can be highly advantageous, for example, when searching for food.
AU - van Drongelen, Ruben
AU - Pal, Anshuman
AU - Goodrich, Carl Peter
AU - Idema, Timon
ID - 7767
IS - 3
JF - Physical Review E
SN - 1539-3755
TI - Collective dynamics of soft active particles
VL - 91
ER -
TY - CONF
AB - In many applications, the data is of rich structure that can be represented by a hypergraph, where the data items are represented by vertices and the associations among items are represented by hyperedges. Equivalently, we are given an input bipartite graph with two types of vertices: items, and associations (which we refer to as topics). We consider the problem of partitioning the set of items into a given number of components such that the maximum number of topics covered by a component is minimized. This is a clustering problem with various applications, e.g. partitioning of a set of information objects such as documents, images, and videos, and load balancing in the context of modern computation platforms.Inthis paper, we focus on the streaming computation model for this problem, in which items arrive online one at a time and each item must be assigned irrevocably to a component at its arrival time. Motivated by scalability requirements, we focus on the class of streaming computation algorithms with memory limited to be at most linear in the number of components. We show that a greedy assignment strategy is able to recover a hidden co-clustering of items under a natural set of recovery conditions. We also report results of an extensive empirical evaluation, which demonstrate that this greedy strategy yields superior performance when compared with alternative approaches.
AU - Alistarh, Dan-Adrian
AU - Iglesias, Jennifer
AU - Vojnović, Milan
ID - 777
TI - Streaming min-max hypergraph partitioning
VL - 2015-January
ER -
TY - GEN
AB - The fact that a disordered material is not constrained in its properties in
the same way as a crystal presents significant and yet largely untapped
potential for novel material design. However, unlike their crystalline
counterparts, disordered solids are not well understood. One of the primary
obstacles is the lack of a theoretical framework for thinking about disorder
and its relation to mechanical properties. To this end, we study an idealized
system of frictionless athermal soft spheres that, when compressed, undergoes a
jamming phase transition with diverging length scales and clean power-law
signatures. This critical point is the cornerstone of a much larger "jamming
scenario" that has the potential to provide the essential theoretical
foundation necessary for a unified understanding of the mechanics of disordered
solids. We begin by showing that jammed sphere packings have a valid linear
regime despite the presence of "contact nonlinearities." We then investigate
the critical nature of the transition, focusing on diverging length scales and
finite-size effects. Next, we argue that jamming plays the same role for
disordered solids as the perfect crystal plays for crystalline solids. Not only
can it be considered an idealized starting point for understanding disordered
materials, but it can even influence systems that have a relatively high amount
of crystalline order. The behavior of solids can thus be thought of as existing
on a spectrum, with the perfect crystal and the jamming transition at opposing
ends. Finally, we introduce a new principle wherein the contribution of an
individual bond to one global property is independent of its contribution to
another. This principle allows the different global responses of a disordered
system to be manipulated independently and provides a great deal of flexibility
in designing materials with unique, textured and tunable properties.
AU - Goodrich, Carl Peter
ID - 7779
T2 - arXiv:1510.08820
TI - Unearthing the anticrystal: Criticality in the linear response of disordered solids
ER -
TY - CONF
AB - Several Hybrid Transactional Memory (HyTM) schemes have recently been proposed to complement the fast, but best-effort nature of Hardware Transactional Memory (HTM) with a slow, reliable software backup. However, the costs of providing concurrency between hardware and software transactions in HyTM are still not well understood. In this paper, we propose a general model for HyTM implementations, which captures the ability of hardware transactions to buffer memory accesses. The model allows us to formally quantify and analyze the amount of overhead (instrumentation) caused by the potential presence of software transactions.We prove that (1) it is impossible to build a strictly serializable HyTM implementation that has both uninstrumented reads and writes, even for very weak progress guarantees, and (2) the instrumentation cost incurred by a hardware transaction in any progressive opaque HyTM is linear in the size of the transaction’s data set.We further describe two implementations which exhibit optimal instrumentation costs for two different progress conditions. In sum, this paper proposes the first formal HyTM model and captures for the first time the trade-off between the degree of hardware-software TM concurrency and the amount of instrumentation overhead.
AU - Alistarh, Dan-Adrian
AU - Kopinsky, Justin
AU - Kuznetsov, Petr
AU - Ravi, Srivatsan
AU - Shavit, Nir
ID - 778
TI - Inherent limitations of hybrid transactional memory
VL - 9363
ER -
TY - CONF
AB - The concurrent memory reclamation problem is that of devising a way for a deallocating thread to verify that no other concurrent threads hold references to a memory block being deallocated. To date, in the absence of automatic garbage collection, there is no satisfactory solution to this problem; existing tracking methods like hazard pointers, reference counters, or epoch-based techniques like RCU, are either prohibitively expensive or require significant programming expertise, to the extent that implementing them efficiently can be worthy of a publication. None of the existing techniques are automatic or even semi-automated. In this paper, we take a new approach to concurrent memory reclamation: instead of manually tracking access to memory locations as done in techniques like hazard pointers, or restricting shared accesses to specific epoch boundaries as in RCU, our algorithm, called ThreadScan, leverages operating system signaling to automatically detect which memory locations are being accessed by concurrent threads. Initial empirical evidence shows that ThreadScan scales surprisingly well and requires negligible programming effort beyond the standard use of Malloc and Free.
AU - Alistarh, Dan-Adrian
AU - Matveev, Alexander
AU - Leiserson, William
AU - Shavit, Nir
ID - 779
TI - ThreadScan: Automatic and scalable memory reclamation
VL - 2015-June
ER -
TY - CONF
AB - Population protocols are networks of finite-state agents, interacting randomly, and updating their states using simple rules. Despite their extreme simplicity, these systems have been shown to cooperatively perform complex computational tasks, such as simulating register machines to compute standard arithmetic functions. The election of a unique leader agent is a key requirement in such computational constructions. Yet, the fastest currently known population protocol for electing a leader only has linear convergence time, and it has recently been shown that no population protocol using a constant number of states per node may overcome this linear bound. In this paper, we give the first population protocol for leader election with polylogarithmic convergence time, using polylogarithmic memory states per node. The protocol structure is quite simple: each node has an associated value, and is either a leader (still in contention) or a minion (following some leader). A leader keeps incrementing its value and “defeats” other leaders in one-to-one interactions, and will drop from contention and become a minion if it meets a leader with higher value. Importantly, a leader also drops out if it meets a minion with higher absolute value. While these rules are quite simple, the proof that this algorithm achieves polylogarithmic convergence time is non-trivial. In particular, the argument combines careful use of concentration inequalities with anti-concentration bounds, showing that the leaders’ values become spread apart as the execution progresses, which in turn implies that straggling leaders get quickly eliminated. We complement our analysis with empirical results, showing that our protocol converges extremely fast, even for large network sizes.
AU - Alistarh, Dan-Adrian
AU - Gelashvili, Rati
ID - 780
TI - Polylogarithmic-time leader election in population protocols
VL - 9135
ER -
TY - CONF
AB - Population protocols, roughly defined as systems consisting of large numbers of simple identical agents, interacting at random and updating their state following simple rules, are an important research topic at the intersection of distributed computing and biology. One of the fundamental tasks that a population protocol may solve is majority: each node starts in one of two states; the goal is for all nodes to reach a correct consensus on which of the two states was initially the majority. Despite considerable research effort, known protocols for this problem are either exact but slow (taking linear parallel time to converge), or fast but approximate (with non-zero probability of error). In this paper, we show that this trade-off between preciasion and speed is not inherent. We present a new protocol called Average and Conquer (AVC) that solves majority ex-actly in expected parallel convergence time O(log n/(sε) + log n log s), where n is the number of nodes, εn is the initial node advantage of the majority state, and s = Ω(log n log log n) is the number of states the protocol employs. This shows that the majority problem can be solved exactly in time poly-logarithmic in n, provided that the memory per node is s = Ω(1/ε + lognlog1/ε). On the negative side, we establish a lower bound of Ω(1/ε) on the expected paraallel convergence time for the case of four memory states per node, and a lower bound of Ω(logn) parallel time for protocols using any number of memory states per node.per node, and a lower bound of (log n) parallel time for protocols using any number of memory states per node.
AU - Alistarh, Dan-Adrian
AU - Gelashvili, Rati
AU - Vojnović, Milan
ID - 781
TI - Fast and exact majority in population protocols
VL - 2015-July
ER -
TY - CONF
AB - In this work, we consider the following random process, mo- Tivated by the analysis of lock-free concurrent algorithms under high memory contention. In each round, a new scheduling step is allocated to one of n threads, according to a distribution p = (p1; p2; : : : ; pn), where thread i is scheduled with probability pi. When some thread first reaches a set threshold of executed steps, it registers a win, completing its current operation, and resets its step count to 1. At the same time, threads whose step count was close to the threshold also get reset because of the win, but to 0 steps, being penalized for almost winning. We are interested in two questions: how often does some thread complete an operation (system latency), and how often does a specific thread complete an operation (individual latency)? We provide asymptotically tight bounds for the system and individual latency of this general concurrency pattern, for arbitrary scheduling distributions p. Surprisingly, a sim- ple characterization exists: in expectation, the system will complete a new operation every Θ(1/p 2) steps, while thread i will complete a new operation every Θ(1/2=p i ) steps. The proof is interesting in its own right, as it requires a careful analysis of how the higher norms of the vector p inuence the thread step counts and latencies in this random process. Our result offers a simple connection between the scheduling distribution and the average performance of concurrent algorithms, which has several applications.
AU - Alistarh, Dan-Adrian
AU - Sauerwald, Thomas
AU - Vojnović, Milan
ID - 782
TI - Lock-Free algorithms under stochastic schedulers
VL - 2015-July
ER -
TY - CONF
AB - The problem of electing a leader from among n contenders is one of the fundamental questions in distributed computing. In its simplest formulation, the task is as follows: given n processors, all participants must eventually return a win or lose indication, such that a single contender may win. Despite a considerable amount of work on leader election, the following question is still open: can we elect a leader in an asynchronous fault-prone system faster than just running a Θ(log n)-time tournament, against a strong adaptive adversary? In this paper, we answer this question in the affirmative, improving on a decades-old upper bound. We introduce two new algorithmic ideas to reduce the time complexity of electing a leader to O(log∗ n), using O(n2) point-to-point messages. A non-trivial application of our algorithm is a new upper bound for the tight renaming problem, assigning n items to the n participants in expected O(log2 n) time and O(n2) messages. We complement our results with lower bound of Ω(n2) messages for solving these two problems, closing the question of their message complexity.
AU - Alistarh, Dan-Adrian
AU - Gelashvili, Rati
AU - Vladu, Adrian
ID - 783
TI - How to elect a leader faster than a tournament
VL - 2015-July
ER -
TY - CONF
AB - We demonstrate an optical switch design that can scale up to a thousand ports with high per-port bandwidth (25 Gbps+) and low switching latency (40 ns). Our design uses a broadcast and select architecture, based on a passive star coupler and fast tunable transceivers. In addition we employ time division multiplexing to achieve very low switching latency. Our demo shows the feasibility of the switch data plane using a small testbed, comprising two transmitters and a receiver, connected through a star coupler.
AU - Alistarh, Dan-Adrian
AU - Ballani, Hitesh
AU - Costa, Paolo
AU - Funnell, Adam
AU - Benjamin, Joshua
AU - Watts, Philip
AU - Thomsen, Benn
ID - 784
SN - 978-1-4503-3542-3
TI - A high-radix, low-latency optical switch for data centers
ER -
TY - JOUR
AB - We prove that nonlinear Gibbs measures can be obtained from the corresponding many-body, grand-canonical, quantum Gibbs states, in a mean-field limit where the temperature T diverges and the interaction strength behaves as 1/T. We proceed by characterizing the interacting Gibbs state as minimizing a functional counting the free-energy relatively to the non-interacting case. We then perform an infinite-dimensional analogue of phase-space semiclassical analysis, using fine properties of the quantum relative entropy, the link between quantum de Finetti measures and upper/lower symbols in a coherent state basis, as well as Berezin-Lieb type inequalities. Our results cover the measure built on the defocusing nonlinear Schrödinger functional on a finite interval, as well as smoother interactions in dimensions d 2.
AU - Lewin, Mathieu
AU - Phan Thanh, Nam
AU - Rougerie, Nicolas
ID - 473
JF - Journal de l'Ecole Polytechnique - Mathematiques
TI - Derivation of nonlinear gibbs measures from many-body quantum mechanics
VL - 2
ER -
TY - JOUR
AB - Dendritic cells are potent antigen-presenting cells endowed with the unique ability to initiate adaptive immune responses upon inflammation. Inflammatory processes are often associated with an increased production of serotonin, which operates by activating specific receptors. However, the functional role of serotonin receptors in regulation of dendritic cell functions is poorly understood. Here, we demonstrate that expression of serotonin receptor 5-HT7 (5-HT7TR) as well as its downstream effector Cdc42 is upregulated in dendritic cells upon maturation. Although dendritic cell maturation was independent of 5-HT7TR, receptor stimulation affected dendritic cell morphology through Cdc42-mediated signaling. In addition, basal activity of 5-HT7TR was required for the proper expression of the chemokine receptor CCR7, which is a key factor that controls dendritic cell migration. Consistent with this, we observed that 5-HT7TR enhances chemotactic motility of dendritic cells in vitro by modulating their directionality and migration velocity. Accordingly, migration of dendritic cells in murine colon explants was abolished after pharmacological receptor inhibition. Our results indicate that there is a crucial role for 5-HT7TR-Cdc42-mediated signaling in the regulation of dendritic cell morphology and motility, suggesting that 5-HT7TR could be a new target for treatment of a variety of inflammatory and immune disorders.
AU - Holst, Katrin
AU - Guseva, Daria
AU - Schindler, Susann
AU - Sixt, Michael K
AU - Braun, Armin
AU - Chopra, Himpriya
AU - Pabst, Oliver
AU - Ponimaskin, Evgeni
ID - 477
IS - 15
JF - Journal of Cell Science
TI - The serotonin receptor 5-HT7R regulates the morphology and migratory properties of dendritic cells
VL - 128
ER -
TY - JOUR
AB - We consider two-player games played on weighted directed graphs with mean-payoff and total-payoff objectives, two classical quantitative objectives. While for single-dimensional games the complexity and memory bounds for both objectives coincide, we show that in contrast to multi-dimensional mean-payoff games that are known to be coNP-complete, multi-dimensional total-payoff games are undecidable. We introduce conservative approximations of these objectives, where the payoff is considered over a local finite window sliding along a play, instead of the whole play. For single dimension, we show that (i) if the window size is polynomial, deciding the winner takes polynomial time, and (ii) the existence of a bounded window can be decided in NP ∩ coNP, and is at least as hard as solving mean-payoff games. For multiple dimensions, we show that (i) the problem with fixed window size is EXPTIME-complete, and (ii) there is no primitive-recursive algorithm to decide the existence of a bounded window.
AU - Chatterjee, Krishnendu
AU - Doyen, Laurent
AU - Randour, Mickael
AU - Raskin, Jean
ID - 523
IS - 6
JF - Information and Computation
TI - Looking at mean-payoff and total-payoff through windows
VL - 242
ER -
TY - JOUR
AB - We consider concurrent games played by two players on a finite-state graph, where in every round the players simultaneously choose a move, and the current state along with the joint moves determine the successor state. We study the most fundamental objective for concurrent games, namely, mean-payoff or limit-average objective, where a reward is associated to each transition, and the goal of player 1 is to maximize the long-run average of the rewards, and the objective of player 2 is strictly the opposite (i.e., the games are zero-sum). The path constraint for player 1 could be qualitative, i.e., the mean-payoff is the maximal reward, or arbitrarily close to it; or quantitative, i.e., a given threshold between the minimal and maximal reward. We consider the computation of the almost-sure (resp. positive) winning sets, where player 1 can ensure that the path constraint is satisfied with probability 1 (resp. positive probability). Almost-sure winning with qualitative constraint exactly corresponds to the question of whether there exists a strategy to ensure that the payoff is the maximal reward of the game. Our main results for qualitative path constraints are as follows: (1) we establish qualitative determinacy results that show that for every state either player 1 has a strategy to ensure almost-sure (resp. positive) winning against all player-2 strategies, or player 2 has a spoiling strategy to falsify almost-sure (resp. positive) winning against all player-1 strategies; (2) we present optimal strategy complexity results that precisely characterize the classes of strategies required for almost-sure and positive winning for both players; and (3) we present quadratic time algorithms to compute the almost-sure and the positive winning sets, matching the best known bound of the algorithms for much simpler problems (such as reachability objectives). For quantitative constraints we show that a polynomial time solution for the almost-sure or the positive winning set would imply a solution to a long-standing open problem (of solving the value problem of turn-based deterministic mean-payoff games) that is not known to be solvable in polynomial time.
AU - Chatterjee, Krishnendu
AU - Ibsen-Jensen, Rasmus
ID - 524
IS - 6
JF - Information and Computation
TI - Qualitative analysis of concurrent mean payoff games
VL - 242
ER -
TY - JOUR
AB - Ethylene is a gaseous phytohormone that plays vital roles in plant growth and development. Previous studies uncovered EIN2 as an essential signal transducer linking ethylene perception on ER to transcriptional regulation in the nucleus through a “cleave and shuttle” model. In this study, we report another mechanism of EIN2-mediated ethylene signaling, whereby EIN2 imposes the translational repression of EBF1 and EBF2 mRNA. We find that the EBF1/2 3′ UTRs mediate EIN2-directed translational repression and identify multiple poly-uridylates (PolyU) motifs as functional cis elements of 3′ UTRs. Furthermore, we demonstrate that ethylene induces EIN2 to associate with 3′ UTRs and target EBF1/2 mRNA to cytoplasmic processing-body (P-body) through interacting with multiple P-body factors, including EIN5 and PABs. Our study illustrates translational regulation as a key step in ethylene signaling and presents mRNA 3′ UTR functioning as a “signal transducer” to sense and relay cellular signaling in plants.
AU - Li, Wenyang
AU - Ma, Mengdi
AU - Feng, Ying
AU - Li, Hongjiang
AU - Wang, Yichuan
AU - Ma, Yutong
AU - Li, Mingzhe
AU - An, Fengying
AU - Guo, Hongwei
ID - 532
IS - 3
JF - Cell
TI - EIN2-directed translational regulation of ethylene signaling in arabidopsis
VL - 163
ER -
TY - GEN
AB - We consider Markov decision processes (MDPs) with multiple limit-average (or mean-payoff) objectives.
There have been two different views: (i) the expectation semantics, where the goal is to optimize the expected mean-payoff objective, and (ii) the satisfaction semantics, where the goal is to maximize the probability of runs such that the mean-payoff value stays above a given vector.
We consider the problem where the goal is to optimize the expectation under the constraint that the satisfaction semantics is ensured, and thus consider a generalization that unifies the existing semantics.
Our problem captures the notion of optimization with respect to strategies that are risk-averse (i.e., ensures certain probabilistic guarantee).
Our main results are algorithms for the decision problem which are always polynomial in the size of the MDP. We also show that an approximation of the Pareto-curve can be computed in time polynomial in the size of the MDP, and the approximation factor, but exponential in the number of dimensions.
Finally, we present a complete characterization of the strategy complexity (in terms of memory bounds and randomization) required to solve our problem.
AU - Chatterjee, Krishnendu
AU - Komarkova, Zuzana
AU - Kretinsky, Jan
ID - 5429
SN - 2664-1690
TI - Unifying two views on multiple mean-payoff objectives in Markov decision processes
ER -
TY - GEN
AB - We consider the core algorithmic problems related to verification of systems with respect to three classical quantitative properties, namely, the mean- payoff property, the ratio property, and the minimum initial credit for energy property. The algorithmic problem given a graph and a quantitative property asks to compute the optimal value (the infimum value over all traces) from every node of the graph. We consider graphs with constant treewidth, and it is well-known that the control-flow graphs of most programs have constant treewidth. Let n denote the number of nodes of a graph, m the number of edges (for constant treewidth graphs m = O ( n ) ) and W the largest absolute value of the weights. Our main theoretical results are as follows. First, for constant treewidth graphs we present an algorithm that approximates the mean-payoff value within a mul- tiplicative factor of ∊ in time O ( n · log( n/∊ )) and linear space, as compared to the classical algorithms that require quadratic time. Second, for the ratio property we present an algorithm that for constant treewidth graphs works in time O ( n · log( | a · b · n | )) = O ( n · log( n · W )) , when the output is a b , as compared to the previously best known algorithm with running time O ( n 2 · log( n · W )) . Third, for the minimum initial credit problem we show that (i) for general graphs the problem can be solved in O ( n 2 · m ) time and the associated decision problem can be solved in O ( n · m ) time, improving the previous known O ( n 3 · m · log( n · W )) and O ( n 2 · m ) bounds, respectively; and (ii) for constant treewidth graphs we present an algorithm that requires O ( n · log n ) time, improving the previous known O ( n 4 · log( n · W )) bound. We have implemented some of our algorithms and show that they present a significant speedup on standard benchmarks.
AU - Chatterjee, Krishnendu
AU - Ibsen-Jensen, Rasmus
AU - Pavlogiannis, Andreas
ID - 5430
SN - 2664-1690
TI - Faster algorithms for quantitative verification in constant treewidth graphs
ER -
TY - GEN
AB - We consider finite-state concurrent stochastic games, played by k>=2 players for an infinite number of rounds, where in every round, each player simultaneously and independently of the other players chooses an action, whereafter the successor state is determined by a probability distribution given by the current state and the chosen actions. We consider reachability objectives that given a target set of states require that some state in the target set is visited, and the dual safety objectives that given a target set require that only states in the target set are visited. We are interested in the complexity of stationary strategies measured by their patience, which is defined as the inverse of the smallest non-zero probability employed.
Our main results are as follows: We show that in two-player zero-sum concurrent stochastic games (with reachability objective for one player and the complementary safety objective for the other player): (i) the optimal bound on the patience of optimal and epsilon-optimal strategies, for both players is doubly exponential; and (ii) even in games with a single non-absorbing state exponential (in the number of actions) patience is necessary. In general we study the class of non-zero-sum games admitting epsilon-Nash equilibria. We show that if there is at least one player with reachability objective, then doubly-exponential patience is needed in general for epsilon-Nash equilibrium strategies, whereas in contrast if all players have safety objectives, then the optimal bound on patience for epsilon-Nash equilibrium strategies is only exponential.
AU - Chatterjee, Krishnendu
AU - Ibsen-Jensen, Rasmus
AU - Hansen, Kristoffer
ID - 5431
SN - 2664-1690
TI - The patience of concurrent stochastic games with safety and reachability objectives
ER -
TY - GEN
AB - Evolution occurs in populations of reproducing individuals. The structure of the population affects the outcome of the evolutionary process. Evolutionary graph theory is a powerful approach to study this phenomenon. There are two graphs. The interaction graph specifies who interacts with whom in the context of evolution.The replacement graph specifies who competes with whom for reproduction.
The vertices of the two graphs are the same, and each vertex corresponds to an individual of the population. A key quantity is the fixation probability of a new mutant. It is defined as the probability that a newly introduced mutant (on a single vertex) generates a lineage of offspring which eventually takes over the entire population of resident individuals. The basic computational questions are as follows: (i) the qualitative question asks whether the fixation probability is positive; and (ii) the quantitative approximation question asks for an approximation of the fixation probability.
Our main results are:
(1) We show that the qualitative question is NP-complete and the quantitative approximation question is #P-hard in the special case when the interaction and the replacement graphs coincide and even with the restriction that the resident individuals do not reproduce (which corresponds to an invading population taking over an empty structure).
(2) We show that in general the qualitative question is PSPACE-complete and the quantitative approximation question is PSPACE-hard and can be solved in exponential time.
AU - Chatterjee, Krishnendu
AU - Ibsen-Jensen, Rasmus
AU - Nowak, Martin
ID - 5432
SN - 2664-1690
TI - The complexity of evolutionary games on graphs
ER -
TY - GEN
AB - DEC-POMDPs extend POMDPs to a multi-agent setting, where several agents operate in an uncertain environment independently to achieve a joint objective. DEC-POMDPs have been studied with finite-horizon and infinite-horizon discounted-sum objectives, and there exist solvers both for exact and approximate solutions. In this work we consider Goal-DEC-POMDPs, where given a set of target states, the objective is to ensure that the target set is reached with minimal cost. We consider the indefinite-horizon (infinite-horizon with either discounted-sum, or undiscounted-sum, where absorbing goal states have zero-cost) problem. We present a new method to solve the problem that extends methods for finite-horizon DEC- POMDPs and the RTDP-Bel approach for POMDPs. We present experimental results on several examples, and show our approach presents promising results.
AU - Anonymous, 1
AU - Anonymous, 2
ID - 5434
SN - 2664-1690
TI - Optimal cost indefinite-horizon reachability in goal DEC-POMDPs
ER -
TY - GEN
AB - We consider Markov decision processes (MDPs) with multiple limit-average (or mean-payoff) objectives.
There have been two different views: (i) the expectation semantics, where the goal is to optimize the expected mean-payoff objective, and (ii) the satisfaction semantics, where the goal is to maximize the probability of runs such that the mean-payoff value stays above a given vector.
We consider the problem where the goal is to optimize the expectation under the constraint that the satisfaction semantics is ensured, and thus consider a generalization that unifies the existing semantics. Our problem captures the notion of optimization with respect to strategies that are risk-averse (i.e., ensures certain probabilistic guarantee).
Our main results are algorithms for the decision problem which are always polynomial in the size of the MDP.
We also show that an approximation of the Pareto-curve can be computed in time polynomial in the size of the MDP, and the approximation factor, but exponential in the number of dimensions. Finally, we present a complete characterization of the strategy complexity (in terms of memory bounds and randomization) required to solve our problem.
AU - Chatterjee, Krishnendu
AU - Komarkova, Zuzana
AU - Kretinsky, Jan
ID - 5435
SN - 2664-1690
TI - Unifying two views on multiple mean-payoff objectives in Markov decision processes
ER -
TY - GEN
AB - Recently there has been a significant effort to handle quantitative properties in formal verification and synthesis. While weighted automata over finite and infinite words provide a natural and flexible framework to express quantitative properties, perhaps surprisingly, some basic system properties such as average response time cannot be expressed using weighted automata, nor in any other know decidable formalism. In this work, we introduce nested weighted automata as a natural extension of weighted automata which makes it possible to express important quantitative properties such as average response time.
In nested weighted automata, a master automaton spins off and collects results from weighted slave automata, each of which computes a quantity along a finite portion of an infinite word. Nested weighted automata can be viewed as the quantitative analogue of monitor automata, which are used in run-time verification. We establish an almost complete decidability picture for the basic decision problems about nested weighted automata, and illustrate their applicability in several domains. In particular, nested weighted automata can be used to decide average response time properties.
AU - Chatterjee, Krishnendu
AU - Henzinger, Thomas A
AU - Otop, Jan
ID - 5436
SN - 2664-1690
TI - Nested weighted automata
ER -
TY - GEN
AB - We consider the core algorithmic problems related to verification of systems with respect to three classical quantitative properties, namely, the mean-payoff property, the ratio property, and the minimum initial credit for energy property.
The algorithmic problem given a graph and a quantitative property asks to compute the optimal value (the infimum value over all traces) from every node of the graph. We consider graphs with constant treewidth, and it is well-known that the control-flow graphs of most programs have constant treewidth. Let $n$ denote the number of nodes of a graph, $m$ the number of edges (for constant treewidth graphs $m=O(n)$) and $W$ the largest absolute value of the weights.
Our main theoretical results are as follows.
First, for constant treewidth graphs we present an algorithm that approximates the mean-payoff value within a multiplicative factor of $\epsilon$ in time $O(n \cdot \log (n/\epsilon))$ and linear space, as compared to the classical algorithms that require quadratic time. Second, for the ratio property we present an algorithm that for constant treewidth graphs works in time $O(n \cdot \log (|a\cdot b|))=O(n\cdot\log (n\cdot W))$, when the output is $\frac{a}{b}$, as compared to the previously best known algorithm with running time $O(n^2 \cdot \log (n\cdot W))$. Third, for the minimum initial credit problem we show that (i)~for general graphs the problem can be solved in $O(n^2\cdot m)$ time and the associated decision problem can be solved in $O(n\cdot m)$ time, improving the previous known $O(n^3\cdot m\cdot \log (n\cdot W))$ and $O(n^2 \cdot m)$ bounds, respectively; and (ii)~for constant treewidth graphs we present an algorithm that requires $O(n\cdot \log n)$ time, improving the previous known $O(n^4 \cdot \log (n \cdot W))$ bound.
We have implemented some of our algorithms and show that they present a significant speedup on standard benchmarks.
AU - Chatterjee, Krishnendu
AU - Ibsen-Jensen, Rasmus
AU - Pavlogiannis, Andreas
ID - 5437
SN - 2664-1690
TI - Faster algorithms for quantitative verification in constant treewidth graphs
ER -
TY - GEN
AB - The edit distance between two words w1, w2 is the minimal number of word operations (letter insertions, deletions, and substitutions) necessary to transform w1 to w2. The edit distance generalizes to languages L1, L2, where the edit distance is the minimal number k such that for every word from L1 there exists a word in L2 with edit distance at most k. We study the edit distance computation problem between pushdown automata and their subclasses.
The problem of computing edit distance to a pushdown automaton is undecidable, and in practice, the interesting question is to compute the edit distance from a pushdown automaton (the implementation, a standard model for programs with recursion) to a regular language (the specification). In this work, we present a complete picture of decidability and complexity for deciding whether, for a given threshold k, the edit distance from a pushdown automaton to a finite automaton is at most k.
AU - Chatterjee, Krishnendu
AU - Henzinger, Thomas A
AU - Ibsen-Jensen, Rasmus
AU - Otop, Jan
ID - 5438
SN - 2664-1690
TI - Edit distance for pushdown automata
ER -
TY - GEN
AB - The target discounted-sum problem is the following: Given a rational discount factor 0 < λ < 1 and three rational values a, b, and t, does there exist a finite or an infinite sequence w ε(a, b)∗ or w ε(a, b)w, such that Σ|w| i=0 w(i)λi equals t? The problem turns out to relate to many fields of mathematics and computer science, and its decidability question is surprisingly hard to solve. We solve the finite version of the problem, and show the hardness of the infinite version, linking it to various areas and open problems in mathematics and computer science: β-expansions, discounted-sum automata, piecewise affine maps, and generalizations of the Cantor set. We provide some partial results to the infinite version, among which are solutions to its restriction to eventually-periodic sequences and to the cases that λ λ 1/2 or λ = 1/n, for every n ε N. We use our results for solving some open problems on discounted-sum automata, among which are the exact-value problem for nondeterministic automata over finite words and the universality and inclusion problems for functional automata.
AU - Boker, Udi
AU - Henzinger, Thomas A
AU - Otop, Jan
ID - 5439
SN - 2664-1690
TI - The target discounted-sum problem
ER -
TY - GEN
AB - Evolution occurs in populations of reproducing individuals. The structure of the population affects the outcome of the evolutionary process. Evolutionary graph theory is a powerful approach to study this phenomenon. There are two graphs. The interaction graph specifies who interacts with whom for payoff in the context of evolution. The replacement graph specifies who competes with whom for reproduction. The vertices of the two graphs are the same, and each vertex corresponds to an individual of the population. The fitness (or the reproductive rate) is a non-negative number, and depends on the payoff. A key quantity is the fixation probability of a new mutant. It is defined as the probability that a newly introduced mutant (on a single vertex) generates a lineage of offspring which eventually takes over the entire population of resident individuals. The basic computational questions are as follows: (i) the qualitative question asks whether the fixation probability is positive; and (ii) the quantitative approximation question asks for an approximation of the fixation probability. Our main results are as follows: First, we consider a special case of the general problem, where the residents do not reproduce. We show that the qualitative question is NP-complete, and the quantitative approximation question is #P-complete, and the hardness results hold even in the special case where the interaction and the replacement graphs coincide. Second, we show that in general both the qualitative and the quantitative approximation questions are PSPACE-complete. The PSPACE-hardness result for quantitative approximation holds even when the fitness is always positive.
AU - Chatterjee, Krishnendu
AU - Ibsen-Jensen, Rasmus
AU - Nowak, Martin
ID - 5440
SN - 2664-1690
TI - The complexity of evolutionary games on graphs
ER -
TY - GEN
AB - We study algorithmic questions for concurrent systems where the transitions are labeled from a complete, closed semiring, and path properties are algebraic with semiring operations. The algebraic path properties can model dataflow analysis problems, the shortest path problem, and many other natural problems that arise in program analysis. We consider that each component of the concurrent system is a graph with constant treewidth, a property satisfied by the controlflow graphs of most programs. We allow for multiple possible queries, which arise naturally in demand driven dataflow analysis. The study of multiple queries allows us to consider the tradeoff between the resource usage of the one-time preprocessing and for each individual query. The traditional approach constructs the product graph of all components and applies the best-known graph algorithm on the product. In this approach, even the answer to a single query requires the transitive closure (i.e., the results of all possible queries), which provides no room for tradeoff between preprocessing and query time. Our main contributions are algorithms that significantly improve the worst-case running time of the traditional approach, and provide various tradeoffs depending on the number of queries. For example, in a concurrent system of two components, the traditional approach requires hexic time in the worst case for answering one query as well as computing the transitive closure, whereas we show that with one-time preprocessing in almost cubic time, each subsequent query can be answered in at most linear time, and even the transitive closure can be computed in almost quartic time. Furthermore, we establish conditional optimality results showing that the worst-case running time of our algorithms cannot be improved without achieving major breakthroughs in graph algorithms (i.e., improving the worst-case bound for the shortest path problem in general graphs). Preliminary experimental results show that our algorithms perform favorably on several benchmarks.
AU - Chatterjee, Krishnendu
AU - Ibsen-Jensen, Rasmus
AU - Goharshady, Amir
AU - Pavlogiannis, Andreas
ID - 5441
SN - 2664-1690
TI - Algorithms for algebraic path properties in concurrent systems of constant treewidth components
ER -
TY - GEN
AB - We study algorithmic questions for concurrent systems where the transitions are labeled from a complete, closed semiring, and path properties are algebraic with semiring operations. The algebraic path properties can model dataflow analysis problems, the shortest path problem, and many other natural properties that arise in program analysis.
We consider that each component of the concurrent system is a graph with constant treewidth, and it is known that the controlflow graphs of most programs have constant treewidth. We allow for multiple possible queries, which arise naturally in demand driven dataflow analysis problems (e.g., alias analysis). The study of multiple queries allows us to consider the tradeoff between the resource usage of the \emph{one-time} preprocessing and for \emph{each individual} query. The traditional approaches construct the product graph of all components and apply the best-known graph algorithm on the product. In the traditional approach, even the answer to a single query requires the transitive closure computation (i.e., the results of all possible queries), which provides no room for tradeoff between preprocessing and query time.
Our main contributions are algorithms that significantly improve the worst-case running time of the traditional approach, and provide various tradeoffs depending on the number of queries. For example, in a concurrent system of two components, the traditional approach requires hexic time in the worst case for answering one query as well as computing the transitive closure, whereas we show that with one-time preprocessing in almost cubic time,
each subsequent query can be answered in at most linear time, and even the transitive closure can be computed in almost quartic time. Furthermore, we establish conditional optimality results that show that the worst-case running times of our algorithms cannot be improved without achieving major breakthroughs in graph algorithms (such as improving
the worst-case bounds for the shortest path problem in general graphs whose current best-known bound has not been improved in five decades). Finally, we provide a prototype implementation of our algorithms which significantly outperforms the existing algorithmic methods on several benchmarks.
AU - Anonymous, 1
AU - Anonymous, 2
AU - Anonymous, 3
AU - Anonymous, 4
ID - 5442
SN - 2664-1690
TI - Algorithms for algebraic path properties in concurrent systems of constant treewidth components
ER -
TY - GEN
AB - POMDPs are standard models for probabilistic planning problems, where an agent interacts with an uncertain environment. We study the problem of almost-sure reachability, where given a set of target states, the question is to decide whether there is a policy to ensure that the target set is reached with probability 1 (almost-surely). While in general the problem is EXPTIME-complete, in many practical cases policies with a small amount of memory suffice. Moreover, the existing solution to the problem is explicit, which first requires to construct explicitly an exponential reduction to a belief-support MDP. In this work, we first study the existence of observation-stationary strategies, which is NP-complete, and then small-memory strategies. We present a symbolic algorithm by an efficient encoding to SAT and using a SAT solver for the problem. We report experimental results demonstrating the scalability of our symbolic (SAT-based) approach.
AU - Chatterjee, Krishnendu
AU - Chmelik, Martin
AU - Davies, Jessica
ID - 5443
SN - 2664-1690
TI - A symbolic SAT-based algorithm for almost-sure reachability with small strategies in POMDPs
ER -
TY - GEN
AB - A comprehensive understanding of the clonal evolution of cancer is critical for understanding neoplasia. Genome-wide sequencing data enables evolutionary studies at unprecedented depth. However, classical phylogenetic methods often struggle with noisy sequencing data of impure DNA samples and fail to detect subclones that have different evolutionary trajectories. We have developed a tool, called Treeomics, that allows us to reconstruct the phylogeny of a cancer with commonly available sequencing technologies. Using Bayesian inference and Integer Linear Programming, robust phylogenies consistent with the biological processes underlying cancer evolution were obtained for pancreatic, ovarian, and prostate cancers. Furthermore, Treeomics correctly identified sequencing artifacts such as those resulting from low statistical power; nearly 7% of variants were misclassified by conventional statistical methods. These artifacts can skew phylogenies by creating illusory tumor heterogeneity among distinct samples. Importantly, we show that the evolutionary trees generated with Treeomics are mathematically optimal.
AU - Reiter, Johannes
AU - Makohon-Moore, Alvin
AU - Gerold, Jeffrey
AU - Bozic, Ivana
AU - Chatterjee, Krishnendu
AU - Iacobuzio-Donahue, Christine
AU - Vogelstein, Bert
AU - Nowak, Martin
ID - 5444
SN - 2664-1690
TI - Reconstructing robust phylogenies of metastatic cancers
ER -
TY - DATA
AB - This repository contains the experimental part of the CAV 2015 publication Counterexample Explanation by Learning Small Strategies in Markov Decision Processes.
We extended the probabilistic model checker PRISM to represent strategies of Markov Decision Processes as Decision Trees.
The archive contains a java executable version of the extended tool (prism_dectree.jar) together with a few examples of the PRISM benchmark library.
To execute the program, please have a look at the README.txt, which provides instructions and further information on the archive.
The archive contains scripts that (if run often enough) reproduces the data presented in the publication.
AU - Fellner, Andreas
ID - 5549
KW - Markov Decision Process
KW - Decision Tree
KW - Probabilistic Verification
KW - Counterexample Explanation
TI - Experimental part of CAV 2015 publication: Counterexample Explanation by Learning Small Strategies in Markov Decision Processes
ER -
TY - JOUR
AB - We present here the first integer-based algorithm for constructing a well-defined lattice sphere specified by integer radius and integer center. The algorithm evolves from a unique correspondence between the lattice points comprising the sphere and the distribution of sum of three square numbers in integer intervals. We characterize these intervals to derive a useful set of recurrences, which, in turn, aids in efficient computation. Each point of the lattice sphere is determined by resorting to only a few primitive operations in the integer domain. The symmetry of its quadraginta octants provides an added advantage by confining the computation to its prima quadraginta octant. Detailed theoretical analysis and experimental results have been furnished to demonstrate its simplicity and elegance.
AU - Biswas, Ranita
AU - Bhowmick, Partha
ID - 5804
IS - 4
JF - Theoretical Computer Science
SN - 0304-3975
TI - From prima quadraginta octant to lattice sphere through primitive integer operations
VL - 624
ER -
TY - JOUR
AU - Biswas, Ranita
AU - Bhowmick, Partha
ID - 5807
IS - 11
JF - Theoretical Computer Science
SN - 0304-3975
TI - On different topological classes of spherical geodesic paths and circles inZ3
VL - 605
ER -
TY - JOUR
AU - Biswas, Ranita
AU - Bhowmick, Partha
ID - 5808
IS - 6-8
JF - The Visual Computer
SN - 0178-2789
TI - Layer the sphere
VL - 31
ER -
TY - JOUR
AB - Transcription of eukaryotic protein-coding genes commences with the assembly of a conserved initiation complex, which consists of RNA polymerase II (Pol II) and the general transcription factors, at promoter DNA. After two decades of research, the structural basis of transcription initiation is emerging. Crystal structures of many components of the initiation complex have been resolved, and structural information on Pol II complexes with general transcription factors has recently been obtained. Although mechanistic details await elucidation, available data outline how Pol II cooperates with the general transcription factors to bind to and open promoter DNA, and how Pol II directs RNA synthesis and escapes from the promoter.
AU - Sainsbury, Sarah
AU - Bernecky, Carrie A
AU - Cramer, Patrick
ID - 594
IS - 3
JF - Nature Reviews Molecular Cell Biology
TI - Structural basis of transcription initiation by RNA polymerase II
VL - 16
ER -
TY - JOUR
AB - Carbon dioxide (CO2) gradients are ubiquitous and provide animals with information about their environment, such as the potential presence of prey or predators. The nematode Caenorhabditis elegans avoids elevated CO2, and previous work identified three neuron pairs called “BAG,” “AFD,” and “ASE” that respond to CO2 stimuli. Using in vivo Ca2+ imaging and behavioral analysis, we show that C. elegans can detect CO2 independently of these sensory pathways. Many of the C. elegans sensory neurons we examined, including the AWC olfactory neurons, the ASJ and ASK gustatory neurons, and the ASH and ADL nociceptors, respond to a rise in CO2 with a rise in Ca2+. In contrast, glial sheath cells harboring the sensory endings of C. elegans’ major chemosensory neurons exhibit strong and sustained decreases in Ca2+ in response to high CO2. Some of these CO2 responses appear to be cell intrinsic. Worms therefore may couple detection of CO2 to that of other cues at the earliest stages of sensory processing. We show that C. elegans persistently suppresses oviposition at high CO2. Hermaphrodite-specific neurons (HSNs), the executive neurons driving egg-laying, are tonically inhibited when CO2 is elevated. CO2 modulates the egg-laying system partly through the AWC olfactory neurons: High CO2 tonically activates AWC by a cGMP-dependent mechanism, and AWC output inhibits the HSNs. Our work shows that CO2 is a more complex sensory cue for C. elegans than previously thought, both in terms of behavior and neural circuitry.
AU - Fenk, Lorenz A.
AU - de Bono, Mario
ID - 6118
IS - 27
JF - Proceedings of the National Academy of Sciences
SN - 0027-8424
TI - Environmental CO2 inhibits Caenorhabditis elegans egg-laying by modulating olfactory neurons and evokes widespread changes in neural activity
VL - 112
ER -
TY - JOUR
AB - Brains organize behavior and physiology to optimize the response to threats or opportunities. We dissect how 21% O2, an indicator of surface exposure, reprograms C. elegans' global state, inducing sustained locomotory arousal and altering expression of neuropeptides, metabolic enzymes, and other non-neural genes. The URX O2-sensing neurons drive arousal at 21% O2 by tonically activating the RMG interneurons. Stimulating RMG is sufficient to switch behavioral state. Ablating the ASH, ADL, or ASK sensory neurons connected to RMG by gap junctions does not disrupt arousal. However, disrupting cation currents in these neurons curtails RMG neurosecretion and arousal. RMG signals high O2 by peptidergic secretion. Neuropeptide reporters reveal neural circuit state, as neurosecretion stimulates neuropeptide expression. Neural imaging in unrestrained animals shows that URX and RMG encode O2 concentration rather than behavior, while the activity of downstream interneurons such as AVB and AIY reflect both O2 levels and the behavior being executed.
AU - Laurent, Patrick
AU - Soltesz, Zoltan
AU - Nelson, Geoffrey M
AU - Chen, Changchun
AU - Arellano-Carbajal, Fausto
AU - Levy, Emmanuel
AU - de Bono, Mario
ID - 6120
JF - eLife
SN - 2050-084X
TI - Decoding a neural circuit controlling global animal state in C. elegans
VL - 4
ER -
TY - JOUR
AB - The osteoclast-associated receptor (OSCAR) is a collagen-binding immune receptor with important roles in dendritic cell maturation and activation of inflammatory monocytes as well as in osteoclastogenesis. The crystal structure of the OSCAR ectodomain is presented, both free and in complex with a consensus triple-helical peptide (THP). The structures revealed a collagen-binding site in each immunoglobulin-like domain (D1 and D2). The THP binds near a predicted collagen-binding groove in D1, but a more extensive interaction with D2 is facilitated by the unusually wide D1-D2 interdomain angle in OSCAR. Direct binding assays, combined with site-directed mutagenesis, confirm that the primary collagen-binding site in OSCAR resides in D2, in marked contrast to the related collagen receptors, glycoprotein VI (GPVI) and leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1). Monomeric OSCAR D1D2 binds to the consensus THP with a KD of 28 µM measured in solution, but shows a higher affinity (KD 1.5 μM) when binding to a solid-phase THP, most likely due to an avidity effect. These data suggest a 2-stage model for the interaction of OSCAR with a collagen fibril, with transient, low-affinity interactions initiated by the membrane-distal D1, followed by firm adhesion to the primary binding site in D2.
AU - Zhou, Long
AU - Hinerman, J. M.
AU - Blaszczyk, M.
AU - Miller, J. L. C.
AU - Conrady, D. G.
AU - Barrow, A. D.
AU - Chirgadze, D. Y.
AU - Bihan, D.
AU - Farndale, R. W.
AU - Herr, A. B.
ID - 6507
IS - 5
JF - Blood
SN - 0006-4971
TI - Structural basis for collagen recognition by the immune receptor OSCAR
VL - 127
ER -
TY - JOUR
AB - Motivated by the significant performance gains which polar codes experience under successive cancellation list decoding, their scaling exponent is studied as a function of the list size. In particular, the error probability is fixed, and the tradeoff between the block length and back-off from capacity is analyzed. A lower bound is provided on the error probability under MAP decoding with list size L for any binary-input memoryless output-symmetric channel and for any class of linear codes such that their minimum distance is unbounded as the block length grows large. Then, it is shown that under MAP decoding, although the introduction of a list can significantly improve the involved constants, the scaling exponent itself, i.e., the speed at which capacity is approached, stays unaffected for any finite list size. In particular, this result applies to polar codes, since their minimum distance tends to infinity as the block length increases. A similar result is proved for genie-aided successive cancellation decoding when transmission takes place over the binary erasure channel, namely, the scaling exponent remains constant for any fixed number of helps from the genie. Note that since genie-aided successive cancellation decoding might be strictly worse than successive cancellation list decoding, the problem of establishing the scaling exponent of the latter remains open.
AU - Mondelli, Marco
AU - Hassani, Hamed
AU - Urbanke, Rudiger
ID - 6736
IS - 9
JF - IEEE Transactions on Information Theory
TI - Scaling exponent of list decoders with applications to polar codes
VL - 61
ER -
TY - JOUR
AB - This paper presents polar coding schemes for the two-user discrete memoryless broadcast channel (DM-BC) which achieve Marton's region with both common and private messages. This is the best achievable rate region known to date, and it is tight for all classes of two-user DM-BCs whose capacity regions are known. To accomplish this task, we first construct polar codes for both the superposition as well as binning strategy. By combining these two schemes, we obtain Marton's region with private messages only. Finally, we show how to handle the case of common information. The proposed coding schemes possess the usual advantages of polar codes, i.e., they have low encoding and decoding complexity and a superpolynomial decay rate of the error probability. We follow the lead of Goela, Abbe, and Gastpar, who recently introduced polar codes emulating the superposition and binning schemes. To align the polar indices, for both schemes, their solution involves some degradedness constraints that are assumed to hold between the auxiliary random variables and channel outputs. To remove these constraints, we consider the transmission of k blocks and employ a chaining construction that guarantees the proper alignment of the polarized indices. The techniques described in this paper are quite general, and they can be adopted to many other multiterminal scenarios whenever there polar indices need to be aligned.
AU - Mondelli, Marco
AU - Hassani, Hamed
AU - Sason, Igal
AU - Urbanke, Rudiger
ID - 6737
IS - 2
JF - IEEE Transactions on Information Theory
TI - Achieving Marton’s region for broadcast channels using polar codes
VL - 61
ER -
TY - JOUR
AB - Torque magnetization measurements on YBa2Cu3Oy (YBCO) at doping y=6.67 (p=0.12), in dc fields (B) up to 33 T and temperatures down to 4.5 K, show that weak diamagnetism persists above the extrapolated irreversibility field Hirr(T=0)≈24 T. The differential susceptibility dM/dB, however, is more rapidly suppressed for B≳16 T than expected from the properties of the low field superconducting state, and saturates at a low value for fields B≳24 T. In addition, torque measurements on a p=0.11 YBCO crystal in pulsed field up to 65 T and temperatures down to 8 K show similar behavior, with no additional features at higher fields. We offer two candidate scenarios to explain these observations: (a) superconductivity survives but is heavily suppressed at high field by competition with charge-density-wave (CDW) order; (b) static superconductivity disappears near 24 T and is followed by a region of fluctuating superconductivity, which causes dM/dB to saturate at high field. The diamagnetic signal observed above 50 T for the p=0.11 crystal at 40 K and below may be caused by changes in the normal state susceptibility rather than bulk or fluctuating superconductivity. There will be orbital (Landau) diamagnetism from electron pockets and possibly a reduction in spin susceptibility caused by the stronger three-dimensional ordered CDW.
AU - Yu, Jing Fei
AU - Ramshaw, B. J.
AU - Kokanović, I.
AU - Modic, Kimberly A
AU - Harrison, N.
AU - Day, James
AU - Liang, Ruixing
AU - Hardy, W. N.
AU - Bonn, D. A.
AU - McCollam, A.
AU - Julian, S. R.
AU - Cooper, J. R.
ID - 7070
IS - 18
JF - Physical Review B
SN - 1098-0121
TI - Magnetization of underdoped YBa2Cu3Oy above the irreversibility field
VL - 92
ER -
TY - JOUR
AB - In this paper, we develop an energy method to study finite speed of propagation and waiting time phenomena for the stochastic porous media equation with linear multiplicative noise in up to three spatial dimensions. Based on a novel iteration technique and on stochastic counterparts of weighted integral estimates used in the deterministic setting, we formulate a sufficient criterion on the growth of initial data which locally guarantees a waiting time phenomenon to occur almost surely. Up to a logarithmic factor, this criterion coincides with the optimal criterion known from the deterministic setting. Our technique can be modified to prove finite speed of propagation as well.
AU - Julian Fischer
AU - Grün, Günther
ID - 1311
IS - 1
JF - SIAM Journal on Mathematical Analysis
TI - Finite speed of propagation and waiting times for the stochastic porous medium equation: A unifying approach
VL - 47
ER -
TY - JOUR
AB - We present an algorithm for the derivation of lower bounds on support propagation for a certain class of nonlinear parabolic equations. We proceed by combining the ideas in some recent papers by the author with the algorithmic construction of entropies due to Jüngel and Matthes, reducing the problem to a quantifier elimination problem. Due to its complexity, the quantifier elimination problem cannot be solved by present exact algorithms. However, by tackling the quantifier elimination problem numerically, in the case of the thin-film equation we are able to improve recent results by the author in the regime of strong slippage n ∈ (1, 2). For certain second-order doubly nonlinear parabolic equations, we are able to extend the known lower bounds on free boundary propagation to the case of irregular oscillatory initial data. Finally, we apply our method to a sixth-order quantum drift-diffusion equation, resulting in an upper bound on the time which it takes for the support to reach every point in the domain.
AU - Julian Fischer
ID - 1313
IS - 1
JF - Interfaces and Free Boundaries
TI - Estimates on front propagation for nonlinear higher-order parabolic equations: An algorithmic approach
VL - 17
ER -
TY - JOUR
AB - We derive a posteriori estimates for the modeling error caused by the assumption of perfect incompressibility in the incompressible Navier-Stokes equation: Real fluids are never perfectly incompressible but always feature at least some low amount of compressibility. Thus, their behavior is described by the compressible Navier-Stokes equation, the pressure being a steep function of the density. We rigorously estimate the difference between an approximate solution to the incompressible Navier-Stokes equation and any weak solution to the compressible Navier-Stokes equation in the sense of Lions (without assuming any additional regularity of solutions). Heuristics and numerical results suggest that our error estimates are of optimal order in the case of "well-behaved" flows and divergence-free approximations of the velocity field. Thus, we expect our estimates to justify the idealization of fluids as perfectly incompressible also in practical situations.
AU - Fischer, Julian L
ID - 1314
IS - 5
JF - SIAM Journal on Numerical Analysis
TI - A posteriori modeling error estimates for the assumption of perfect incompressibility in the Navier-Stokes equation
VL - 53
ER -
TY - JOUR
AB - In the present work we introduce the notion of a renormalized solution for reaction–diffusion systems with entropy-dissipating reactions. We establish the global existence of renormalized solutions. In the case of integrable reaction terms our notion of a renormalized solution reduces to the usual notion of a weak solution. Our existence result in particular covers all reaction–diffusion systems involving a single reversible reaction with mass-action kinetics and (possibly species-dependent) Fick-law diffusion; more generally, it covers the case of systems of reversible reactions with mass-action kinetics which satisfy the detailed balance condition. For such equations the existence of any kind of solution in general was an open problem, thereby motivating the study of renormalized solutions.
AU - Julian Fischer
ID - 1316
IS - 1
JF - Archive for Rational Mechanics and Analysis
TI - Global existence of renormalized solutions to entropy-dissipating reaction–diffusion systems
VL - 218
ER -
TY - JOUR
AB - In plants, vacuolar H+-ATPase (V-ATPase) activity acidifies both the trans-Golgi network/early endosome (TGN/EE) and the vacuole. This dual V-ATPase function has impeded our understanding of how the pH homeostasis within the plant TGN/EE controls exo- and endocytosis. Here, we show that the weak V-ATPase mutant deetiolated3 (det3) displayed a pH increase in the TGN/EE, but not in the vacuole, strongly impairing secretion and recycling of the brassinosteroid receptor and the cellulose synthase complexes to the plasma membrane, in contrast to mutants lacking tonoplast-localized V-ATPase activity only. The brassinosteroid insensitivity and the cellulose deficiency defects in det3 were tightly correlated with reduced Golgi and TGN/EE motility. Thus, our results provide strong evidence that acidification of the TGN/EE, but not of the vacuole, is indispensable for functional secretion and recycling in plants.
AU - Yu, Luo
AU - Scholl, Stefan
AU - Doering, Anett
AU - Yi, Zhang
AU - Irani, Niloufer
AU - Di Rubbo, Simone
AU - Neumetzler, Lutz
AU - Krishnamoorthy, Praveen
AU - Van Houtte, Isabelle
AU - Mylle, Evelien
AU - Bischoff, Volker
AU - Vernhettes, Samantha
AU - Winne, Johan
AU - Friml, Jirí
AU - Stierhof, York
AU - Schumacher, Karin
AU - Persson, Staffan
AU - Russinova, Eugenia
ID - 1383
IS - 7
JF - Nature Plants
TI - V-ATPase activity in the TGN/EE is required for exocytosis and recycling in Arabidopsis
VL - 1
ER -
TY - THES
AB - This thesis is concerned with the computation and approximation of intrinsic volumes. Given a smooth body M and a certain digital approximation of it, we develop algorithms to approximate various intrinsic volumes of M using only measurements taken from its digital approximations. The crucial idea behind our novel algorithms is to link the recent theory of persistent homology to the theory of intrinsic volumes via the Crofton formula from integral geometry and, in particular, via Euler characteristic computations. Our main contributions are a multigrid convergent digital algorithm to compute the first intrinsic volume of a solid body in R^n as well as an appropriate integration pipeline to approximate integral-geometric integrals defined over the Grassmannian manifold.
AU - Pausinger, Florian
ID - 1399
TI - On the approximation of intrinsic volumes
ER -
TY - THES
AB - Cancer results from an uncontrolled growth of abnormal cells. Sequentially accumulated genetic and epigenetic alterations decrease cell death and increase cell replication. We used mathematical models to quantify the effect of driver gene mutations. The recently developed targeted therapies can lead to dramatic regressions. However, in solid cancers, clinical responses are often short-lived because resistant cancer cells evolve. We estimated that approximately 50 different mutations can confer resistance to a typical targeted therapeutic agent. We find that resistant cells are likely to be present in expanded subclones before the start of the treatment. The dominant strategy to prevent the evolution of resistance is combination therapy. Our analytical results suggest that in most patients, dual therapy, but not monotherapy, can result in long-term disease control. However, long-term control can only occur if there are no possible mutations in the genome that can cause cross-resistance to both drugs. Furthermore, we showed that simultaneous therapy with two drugs is much more likely to result in long-term disease control than sequential therapy with the same drugs. To improve our understanding of the underlying subclonal evolution we reconstruct the evolutionary history of a patient's cancer from next-generation sequencing data of spatially-distinct DNA samples. Using a quantitative measure of genetic relatedness, we found that pancreatic cancers and their metastases demonstrated a higher level of relatedness than that expected for any two cells randomly taken from a normal tissue. This minimal amount of genetic divergence among advanced lesions indicates that genetic heterogeneity, when quantitatively defined, is not a fundamental feature of the natural history of untreated pancreatic cancers. Our newly developed, phylogenomic tool Treeomics finds evidence for seeding patterns of metastases and can directly be used to discover rules governing the evolution of solid malignancies to transform cancer into a more predictable disease.
AU - Reiter, Johannes
ID - 1400
TI - The subclonal evolution of cancer
ER -
TY - CONF
AB - We consider the problem of statistical computations with persistence diagrams, a summary representation of topological features in data. These diagrams encode persistent homology, a widely used invariant in topological data analysis. While several avenues towards a statistical treatment of the diagrams have been explored recently, we follow an alternative route that is motivated by the success of methods based on the embedding of probability measures into reproducing kernel Hilbert spaces. In fact, a positive definite kernel on persistence diagrams has recently been proposed, connecting persistent homology to popular kernel-based learning techniques such as support vector machines. However, important properties of that kernel enabling a principled use in the context of probability measure embeddings remain to be explored. Our contribution is to close this gap by proving universality of a variant of the original kernel, and to demonstrate its effective use in twosample hypothesis testing on synthetic as well as real-world data.
AU - Kwitt, Roland
AU - Huber, Stefan
AU - Niethammer, Marc
AU - Lin, Weili
AU - Bauer, Ulrich
ID - 1424
TI - Statistical topological data analysis-A kernel perspective
VL - 28
ER -
TY - CONF
AB - In this work we aim at extending the theoretical foundations of lifelong learning. Previous work analyzing this scenario is based on the assumption that learning tasks are sampled i.i.d. from a task environment or limited to strongly constrained data distributions. Instead, we study two scenarios when lifelong learning is possible, even though the observed tasks do not form an i.i.d. sample: first, when they are sampled from the same environment, but possibly with dependencies, and second, when the task environment is allowed to change over time in a consistent way. In the first case we prove a PAC-Bayesian theorem that can be seen as a direct generalization of the analogous previous result for the i.i.d. case. For the second scenario we propose to learn an inductive bias in form of a transfer procedure. We present a generalization bound and show on a toy example how it can be used to identify a beneficial transfer algorithm.
AU - Pentina, Anastasia
AU - Lampert, Christoph
ID - 1425
TI - Lifelong learning with non-i.i.d. tasks
VL - 2015
ER -
TY - CONF
AB - Evolutionary algorithms (EAs) form a popular optimisation paradigm inspired by natural evolution. In recent years the field of evolutionary computation has developed a rigorous analytical theory to analyse their runtime on many illustrative problems. Here we apply this theory to a simple model of natural evolution. In the Strong Selection Weak Mutation (SSWM) evolutionary regime the time between occurrence of new mutations is much longer than the time it takes for a new beneficial mutation to take over the population. In this situation, the population only contains copies of one genotype and evolution can be modelled as a (1+1)-type process where the probability of accepting a new genotype (improvements or worsenings) depends on the change in fitness. We present an initial runtime analysis of SSWM, quantifying its performance for various parameters and investigating differences to the (1+1) EA. We show that SSWM can have a moderate advantage over the (1+1) EA at crossing fitness valleys and study an example where SSWM outperforms the (1+1) EA by taking advantage of information on the fitness gradient.
AU - Paixao, Tiago
AU - Sudholt, Dirk
AU - Heredia, Jorge
AU - Trubenova, Barbora
ID - 1430
T2 - Proceedings of the 2015 Annual Conference on Genetic and Evolutionary Computation
TI - First steps towards a runtime comparison of natural and artificial evolution
ER -