TY - JOUR
AB - We consider higher-dimensional versions of Kannan and Lipton's Orbit Problem - determining whether a target vector space V may be reached from a starting point x under repeated applications of a linear transformation A. Answering two questions posed by Kannan and Lipton in the 1980s, we show that when V has dimension one, this problem is solvable in polynomial time, and when V has dimension two or three, the problem is in NPRP.
AU - Chonev, Ventsislav K
AU - Ouaknine, Joël
AU - Worrell, James
ID - 1380
IS - 3
JF - Journal of the ACM
TI - On the complexity of the orbit problem
VL - 63
ER -
TY - CONF
AB - Motivated by Tverberg-type problems in topological combinatorics and by classical results about embeddings (maps without double points), we study the question whether a finite simplicial complex K can be mapped into double-struck Rd without higher-multiplicity intersections. We focus on conditions for the existence of almost r-embeddings, i.e., maps f : K → double-struck Rd such that f(σ1) ∩ ⋯ ∩ f(σr) = ∅ whenever σ1, ..., σr are pairwise disjoint simplices of K. Generalizing the classical Haefliger-Weber embeddability criterion, we show that a well-known necessary deleted product condition for the existence of almost r-embeddings is sufficient in a suitable r-metastable range of dimensions: If rd ≥ (r + 1) dim K + 3, then there exists an almost r-embedding K → double-struck Rd if and only if there exists an equivariant map (K)Δ r → Sr Sd(r-1)-1, where (K)Δ r is the deleted r-fold product of K, the target Sd(r-1)-1 is the sphere of dimension d(r - 1) - 1, and Sr is the symmetric group. This significantly extends one of the main results of our previous paper (which treated the special case where d = rk and dim K = (r - 1)k for some k ≥ 3), and settles an open question raised there.
AU - Mabillard, Isaac
AU - Wagner, Uli
ID - 1381
TI - Eliminating higher-multiplicity intersections, II. The deleted product criterion in the r-metastable range
VL - 51
ER -
TY - JOUR
AB - Background and aims Angiosperms display remarkable diversity in flower colour, implying that transitions between pigmentation phenotypes must have been common. Despite progress in understanding transitions between anthocyanin (blue, purple, pink or red) and unpigmented (white) flowers, little is known about the evolutionary patterns of flower-colour transitions in lineages with both yellow and anthocyanin-pigmented flowers. This study investigates the relative rates of evolutionary transitions between different combinations of yellow- and anthocyanin-pigmentation phenotypes in the tribe Antirrhineae. Methods We surveyed taxonomic literature for data on anthocyanin and yellow floral pigmentation for 369 species across the tribe. We then reconstructed the phylogeny of 169 taxa and used phylogenetic comparative methods to estimate transition rates among pigmentation phenotypes across the phylogeny. Key Results In contrast to previous studies we found a bias towards transitions involving a gain in pigmentation, although transitions to phenotypes with both anthocyanin and yellow taxa are nevertheless extremely rare. Despite the dominance of yellow and anthocyanin-pigmented taxa, transitions between these phenotypes are constrained to move through a white intermediate stage, whereas transitions to double-pigmentation are very rare. The most abundant transitions are between anthocyanin-pigmented and unpigmented flowers, and similarly the most abundant polymorphic taxa were those with anthocyanin-pigmented and unpigmented flowers. Conclusions Our findings show that pigment evolution is limited by the presence of other floral pigments. This interaction between anthocyanin and yellow pigments constrains the breadth of potential floral diversity observed in nature. In particular, they suggest that selection has repeatedly acted to promote the spread of single-pigmented phenotypes across the Antirrhineae phylogeny. Furthermore, the correlation between transition rates and polymorphism suggests that the forces causing and maintaining variance in the short term reflect evolutionary processes on longer time scales.
AU - Ellis, Thomas
AU - Field, David
ID - 1382
IS - 7
JF - Annals of Botany
TI - Repeated gains in yellow and anthocyanin pigmentation in flower colour transitions in the Antirrhineae
VL - 117
ER -
TY - CONF
AB - The continuous evolution of a wide variety of systems, including continous-time Markov chains and linear hybrid automata, can be
described in terms of linear differential equations. In this paper we study the decision problem of whether the solution x(t) of a system of linear differential equations dx/dt = Ax reaches a target halfspace infinitely often. This recurrent reachability problem can
equivalently be formulated as the following Infinite Zeros Problem: does a real-valued function f:R≥0 --> R satisfying a given linear
differential equation have infinitely many zeros? Our main decidability result is that if the differential equation has order at most 7, then the Infinite Zeros Problem is decidable. On the other hand, we show that a decision procedure for the Infinite Zeros Problem at order 9 (and above) would entail a major breakthrough in Diophantine Approximation, specifically an algorithm for computing the Lagrange constants of arbitrary real algebraic numbers to arbitrary precision.
AU - Chonev, Ventsislav K
AU - Ouaknine, Joël
AU - Worrell, James
ID - 1389
T2 - LICS '16
TI - On recurrent reachability for continuous linear dynamical systems
ER -
TY - CONF
AB - The goal of automatic program repair is to identify a set of syntactic changes that can turn a program that is incorrect with respect
to a given specification into a correct one. Existing program repair techniques typically aim to find any program that meets the given specification. Such “best-effort” strategies can end up generating a program that is quite different from the original one. Novel techniques have been proposed to compute syntactically minimal program fixes, but the smallest syntactic fix to a program can still significantly alter the original program’s behaviour. We propose a new approach to program repair based on program distances, which can quantify changes not only to the program syntax but also to the program semantics. We call this the quantitative program repair problem where the “optimal” repair is derived using multiple distances. We implement a solution to the quantitative repair
problem in a prototype tool called Qlose
(Quantitatively close), using the program synthesizer Sketch. We evaluate the effectiveness of different distances in obtaining desirable repairs by evaluating
Qlose on programs taken from educational tools such as CodeHunt and edX.
AU - D'Antoni, Loris
AU - Samanta, Roopsha
AU - Singh, Rishabh
ID - 1390
TI - QLOSE: Program repair with quantitative objectives
VL - 9780
ER -
TY - CONF
AB - We present an extension to the quantifier-free theory of integer arrays which allows us to express counting. The properties expressible in Array Folds Logic (AFL) include statements such as "the first array cell contains the array length," and "the array contains equally many minimal and maximal elements." These properties cannot be expressed in quantified fragments of the theory of arrays, nor in the theory of concatenation. Using reduction to counter machines, we show that the satisfiability problem of AFL is PSPACE-complete, and with a natural restriction the complexity decreases to NP. We also show that adding either universal quantifiers or concatenation leads to undecidability.
AFL contains terms that fold a function over an array. We demonstrate that folding, a well-known concept from functional languages, allows us to concisely summarize loops that count over arrays, which occurs frequently in real-life programs. We provide a tool that can discharge proof obligations in AFL, and we demonstrate on practical examples that our decision procedure can solve a broad range of problems in symbolic testing and program verification.
AU - Daca, Przemyslaw
AU - Henzinger, Thomas A
AU - Kupriyanov, Andrey
ID - 1391
TI - Array folds logic
VL - 9780
ER -
TY - JOUR
AB - The solution space of genome-scale models of cellular metabolism provides a map between physically
viable flux configurations and cellular metabolic phenotypes described, at the most basic level, by the
corresponding growth rates. By sampling the solution space of E. coliʼs metabolic network, we show
that empirical growth rate distributions recently obtained in experiments at single-cell resolution can
be explained in terms of a trade-off between the higher fitness of fast-growing phenotypes and the
higher entropy of slow-growing ones. Based on this, we propose a minimal model for the evolution of
a large bacterial population that captures this trade-off. The scaling relationships observed in
experiments encode, in such frameworks, for the same distance from the maximum achievable growth
rate, the same degree of growth rate maximization, and/or the same rate of phenotypic change. Being
grounded on genome-scale metabolic network reconstructions, these results allow for multiple
implications and extensions in spite of the underlying conceptual simplicity.
AU - De Martino, Daniele
AU - Capuani, Fabrizio
AU - De Martino, Andrea
ID - 1394
IS - 3
JF - Physical Biology
TI - Growth against entropy in bacterial metabolism: the phenotypic trade-off behind empirical growth rate distributions in E. coli
VL - 13
ER -
TY - THES
AB - CA3 pyramidal neurons are thought to pay a key role in memory storage and pattern completion by activity-dependent synaptic plasticity between CA3-CA3 recurrent excitatory synapses. To examine the induction rules of synaptic plasticity at CA3-CA3 synapses, we performed whole-cell patch-clamp recordings in acute hippocampal slices from rats (postnatal 21-24 days) at room temperature. Compound excitatory postsynaptic potentials (ESPSs) were recorded by tract stimulation in stratum oriens in the presence of 10 µM gabazine. High-frequency stimulation (HFS) induced N-methyl-D-aspartate (NMDA) receptor-dependent long-term potentiation (LTP). Although LTP by HFS did not requier postsynaptic spikes, it was blocked by Na+-channel blockers suggesting that local active processes (e.g.) dendritic spikes) may contribute to LTP induction without requirement of a somatic action potential (AP). We next examined the properties of spike timing-dependent plasticity (STDP) at CA3-CA3 synapses. Unexpectedly, low-frequency pairing of EPSPs and backpropagated action potentialy (bAPs) induced LTP, independent of temporal order. The STDP curve was symmetric and broad, with a half-width of ~150 ms. Consistent with these specific STDP induction properties, post-presynaptic sequences led to a supralinear summation of spine [Ca2+] transients. Furthermore, in autoassociative network models, storage and recall was substantially more robust with symmetric than with asymmetric STDP rules. In conclusion, we found associative forms of LTP at CA3-CA3 recurrent collateral synapses with distinct induction rules. LTP induced by HFS may be associated with dendritic spikes. In contrast, low frequency pairing of pre- and postsynaptic activity induced LTP only if EPSP-AP were temporally very close. Together, these induction mechanisms of synaptiic plasticity may contribute to memory storage in the CA3-CA3 microcircuit at different ranges of activity.
AU - Mishra, Rajiv Kumar
ID - 1396
TI - Synaptic plasticity rules at CA3-CA3 recurrent synapses in hippocampus
ER -
TY - THES
AB - We study partially observable Markov decision processes (POMDPs) with objectives used in verification and artificial intelligence. The qualitative analysis problem given a POMDP and an objective asks whether there is a strategy (policy) to ensure that the objective is satisfied almost surely (with probability 1), resp. with positive probability (with probability greater than 0). For POMDPs with limit-average payoff, where a reward value in the interval [0,1] is associated to 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 limit-average constraint defines the set of paths where the payoff is at least a given threshold L1 = 1. Our main results for qualitative limit-average constraint under almost-sure winning 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 limit-average constraints we show that the problem of deciding the existence of a finite-memory controller is undecidable. We present a prototype implementation of our EXPTIME algorithm. For POMDPs with w-regular conditions specified as parity objectives, while the qualitative analysis problems are known to be undecidable even for very special case of parity objectives, we establish decidability (with optimal complexity) of the qualitative analysis problems for POMDPs with parity objectives under finite-memory strategies. We establish optimal (exponential) memory bounds and EXPTIME-completeness of the qualitative analysis problems under finite-memory strategies for POMDPs with parity objectives. Based on our theoretical algorithms we also present a practical approach, where we design heuristics to deal with the exponential complexity, and have applied our implementation on a number of well-known POMDP examples for robotics applications. For POMDPs with a set of target states and an integer cost associated with every transition, we study the optimization objective that asks to minimize the expected total cost of reaching a state in the target set, while ensuring that the target set is reached almost surely. We show that for general integer costs approximating the optimal cost is undecidable. For positive costs, our results are as follows: (i) we establish matching lower and upper bounds for the optimal cost, both double and exponential in the POMDP state space size; (ii) we show that the problem of approximating the optimal cost is decidable and present approximation algorithms that extend existing algorithms for POMDPs with finite-horizon objectives. We show experimentally that it performs well in many examples of interest. We study more deeply the problem of almost-sure reachability, where given a set of target states, the question is to decide whether there is a strategy to ensure that the target set is reached almost surely. While in general the problem EXPTIME-complete, in many practical cases strategies 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. 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. Decentralized POMDPs (DEC-POMDPs) extend POMDPs to a multi-agent setting, where several agents operate in an uncertain environment independently to achieve a joint objective. 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 and novel method to solve the problem that extends methods for finite-horizon DEC-POMDPs and the real-time dynamic programming approach for POMDPs. We present experimental results on several examples, and show that our approach presents promising results. In the end we present a short summary of a few other results related to verification of MDPs and POMDPs.
AU - Chmelik, Martin
ID - 1397
TI - Algorithms for partially observable markov decision processes
ER -
TY - THES
AB - Hybrid zones represent evolutionary laboratories, where recombination brings together alleles in combinations which have not previously been tested by selection. This provides an excellent opportunity to test the effect of molecular variation on fitness, and how this variation is able to spread through populations in a natural context. The snapdragon Antirrhinum majus is polymorphic in the wild for two loci controlling the distribution of yellow and magenta floral pigments. Where the yellow A. m. striatum and the magenta A. m. pseudomajus meet along a valley in the Spanish Pyrenees they form a stable hybrid zone Alleles at these loci recombine to give striking transgressive variation for flower colour. The sharp transition in phenotype over ~1km implies strong selection maintaining the hybrid zone. An indirect assay of pollinator visitation in the field found that pollinators forage in a positive-frequency dependent manner on Antirrhinum, matching previous data on fruit set. Experimental arrays and paternity analysis of wild-pollinated seeds demonstrated assortative mating for pigmentation alleles, and that pollinator behaviour alone is sufficient to explain this pattern. Selection by pollinators should be sufficiently strong to maintain the hybrid zone, although other mechanisms may be at work. At a broader scale I examined evolutionary transitions between yellow and anthocyanin pigmentation in the tribe Antirrhinae, and found that selection has acted strate that pollinators are a major determinant of reproductive success and mating patterns in wild Antirrhinum.
AU - Ellis, Thomas
ID - 1398
TI - The role of pollinator-mediated selection in the maintenance of a flower color polymorphism in an Antirrhinum majus hybrid zone
ER -
TY - JOUR
AB - The concept of well group in a special but important case captures homological properties of the zero set of a continuous map (Formula presented.) on a compact space K that are invariant with respect to perturbations of f. The perturbations are arbitrary continuous maps within (Formula presented.) distance r from f for a given (Formula presented.). The main drawback of the approach is that the computability of well groups was shown only when (Formula presented.) or (Formula presented.). Our contribution to the theory of well groups is twofold: on the one hand we improve on the computability issue, but on the other hand we present a range of examples where the well groups are incomplete invariants, that is, fail to capture certain important robust properties of the zero set. For the first part, we identify a computable subgroup of the well group that is obtained by cap product with the pullback of the orientation of (Formula presented.) by f. In other words, well groups can be algorithmically approximated from below. When f is smooth and (Formula presented.), our approximation of the (Formula presented.)th well group is exact. For the second part, we find examples of maps (Formula presented.) with all well groups isomorphic but whose perturbations have different zero sets. We discuss on a possible replacement of the well groups of vector valued maps by an invariant of a better descriptive power and computability status.
AU - Franek, Peter
AU - Krcál, Marek
ID - 1408
IS - 1
JF - Discrete & Computational Geometry
TI - On computability and triviality of well groups
VL - 56
ER -
TY - JOUR
AU - Abbott, Richard
AU - Barton, Nicholas H
AU - Good, Jeffrey
ID - 1409
IS - 11
JF - Molecular Ecology
TI - Genomics of hybridization and its evolutionary consequences
VL - 25
ER -
TY - JOUR
AB - The pollen grains arise after meiosis of pollen mother cells within the anthers. A series of complex structural changes follows, generating mature pollen grains capable of performing the double fertilization of the female megasporophyte. Several signaling molecules, including hormones and lipids, have been involved in the regulation and appropriate control of pollen development. Phosphatidylinositol 4-phophate 5-kinases (PIP5K), which catalyze the biosynthesis of the phosphoinositide PtdIns(4,5)P2, are important for tip polar growth of root hairs and pollen tubes, embryo development, vegetative plant growth, and responses to the environment. Here, we report a role of PIP5Ks during microgametogenesis. PIP5K1 and PIP5K2 are expressed during early stages of pollen development and their transcriptional activity respond to auxin in pollen grains. Early male gametophytic lethality to certain grade was observed in both pip5k1-/- and pip5k2-/- single mutants. The number of pip5k mutant alleles is directly related to the frequency of aborted pollen grains suggesting the two genes are involved in the same function. Indeed PIP5K1 and PIP5K2 are functionally redundant since homozygous double mutants did not render viable pollen grains. The loss of function of PIP5K1 and PIP5K2results in defects in vacuole morphology in pollen at the later stages and epidermal root cells. Our results show that PIP5K1, PIP5K2 and phosphoinositide signaling are important cues for early developmental stages and vacuole formation during microgametogenesis.
AU - Ugalde, José
AU - Rodríguez Furlán, Cecilia
AU - De Rycke, Riet
AU - Norambuena, Lorena
AU - Friml, Jirí
AU - León, Gabriel
AU - Tejos, Ricardo
ID - 1410
JF - Plant Science
TI - Phosphatidylinositol 4-phosphate 5-kinases 1 and 2 are involved in the regulation of vacuole morphology during Arabidopsis thaliana pollen development
VL - 250
ER -
TY - JOUR
AB - We consider two systems (α1, …, αm) and (β1, …,βn) of simple curves drawn on a compact two-dimensional surface M with boundary. Each αi and each βj is either an arc meeting the boundary of M at its two endpoints, or a closed curve. The αi are pairwise disjoint except for possibly sharing endpoints, and similarly for the βj. We want to “untangle” the βj from the ai by a self-homeomorphism of M; more precisely, we seek a homeomorphism φ:M→M fixing the boundary of M pointwise such that the total number of crossings of the ai with the φ(βj) is as small as possible. This problem is motivated by an application in the algorithmic theory of embeddings and 3-manifolds. We prove that if M is planar, i.e., a sphere with h ≥ 0 boundary components (“holes”), then O(mn) crossings can be achieved (independently of h), which is asymptotically tight, as an easy lower bound shows. In general, for an arbitrary (orientable or nonorientable) surface M with h holes and of (orientable or nonorientable) genus g ≥ 0, we obtain an O((m + n)4) upper bound, again independent of h and g. The proofs rely, among other things, on a result concerning simultaneous planar drawings of graphs by Erten and Kobourov.
AU - Matoušek, Jiří
AU - Sedgwick, Eric
AU - Tancer, Martin
AU - Wagner, Uli
ID - 1411
IS - 1
JF - Israel Journal of Mathematics
TI - Untangling two systems of noncrossing curves
VL - 212
ER -
TY - JOUR
AB - Combining high-resolution level set surface tracking with lower resolution physics is an inexpensive method for achieving highly detailed liquid animations. Unfortunately, the inherent resolution mismatch introduces several types of disturbing visual artifacts. We identify the primary sources of these artifacts and present simple, efficient, and practical solutions to address them. First, we propose an unconditionally stable filtering method that selectively removes sub-grid surface artifacts not seen by the fluid physics, while preserving fine detail in dynamic splashing regions. It provides comparable results to recent error-correction techniques at lower cost, without substepping, and with better scaling behavior. Second, we show how a modified narrow-band scheme can ensure accurate free surface boundary conditions in the presence of large resolution mismatches. Our scheme preserves the efficiency of the narrow-band methodology, while eliminating objectionable stairstep artifacts observed in prior work. Third, we demonstrate that the use of linear interpolation of velocity during advection of the high-resolution level set surface is responsible for visible grid-aligned kinks; we therefore advocate higher-order velocity interpolation, and show that it dramatically reduces this artifact. While these three contributions are orthogonal, our results demonstrate that taken together they efficiently address the dominant sources of visual artifacts arising with high-resolution embedded liquid surfaces; the proposed approach offers improved visual quality, a straightforward implementation, and substantially greater scalability than competing methods.
AU - Goldade, Ryan
AU - Batty, Christopher
AU - Wojtan, Christopher J
ID - 1412
IS - 2
JF - Computer Graphics Forum
TI - A practical method for high-resolution embedded liquid surfaces
VL - 35
ER -
TY - JOUR
AB - This paper generalizes the well-known Diffusion Curves Images (DCI), which are composed of a set of Bezier curves with colors specified on either side. These colors are diffused as Laplace functions over the image domain, which results in smooth color gradients interrupted by the Bezier curves. Our new formulation allows for more color control away from the boundary, providing a similar expressive power as recent Bilaplace image models without introducing associated issues and computational costs. The new model is based on a special Laplace function blending and a new edge blur formulation. We demonstrate that given some user-defined boundary curves over an input raster image, fitting colors and edge blur from the image to the new model and subsequent editing and animation is equally convenient as with DCIs. Numerous examples and comparisons to DCIs are presented.
AU - Jeschke, Stefan
ID - 1413
IS - 2
JF - Computer Graphics Forum
TI - Generalized diffusion curves: An improved vector representation for smooth-shaded images
VL - 35
ER -
TY - JOUR
AB - In this paper, we present a method to model hyperelasticity that is well suited for representing the nonlinearity of real-world objects, as well as for estimating it from deformation examples. Previous approaches suffer several limitations, such as lack of integrability of elastic forces, failure to enforce energy convexity, lack of robustness of parameter estimation, or difficulty to model cross-modal effects. Our method avoids these problems by relying on a general energy-based definition of elastic properties. The accuracy of the resulting elastic model is maximized by defining an additive model of separable energy terms, which allow progressive parameter estimation. In addition, our method supports efficient modeling of extreme nonlinearities thanks to energy-limiting constraints. We combine our energy-based model with an optimization method to estimate model parameters from force-deformation examples, and we show successful modeling of diverse deformable objects, including cloth, human finger skin, and internal human anatomy in a medical imaging application.
AU - Miguel Villalba, Eder
AU - Miraut, David
AU - Otaduy, Miguel
ID - 1414
IS - 2
JF - Computer Graphics Forum
TI - Modeling and estimation of energy-based hyperelastic objects
VL - 35
ER -
TY - JOUR
AB - The Fluid Implicit Particle method (FLIP) for liquid simulations uses particles to reduce numerical dissipation and provide important visual cues for events like complex splashes and small-scale features near the liquid surface. Unfortunately, FLIP simulations can be computationally expensive, because they require a dense sampling of particles to fill the entire liquid volume. Furthermore, the vast majority of these FLIP particles contribute nothing to the fluid's visual appearance, especially for larger volumes of liquid. We present a method that only uses FLIP particles within a narrow band of the liquid surface, while efficiently representing the remaining inner volume on a regular grid. We show that a naïve realization of this idea introduces unstable and uncontrollable energy fluctuations, and we propose a novel coupling scheme between FLIP particles and regular grid which overcomes this problem. Our method drastically reduces the particle count and simulation times while yielding results that are nearly indistinguishable from regular FLIP simulations. Our approach is easy to integrate into any existing FLIP implementation.
AU - Ferstl, Florian
AU - Ando, Ryoichi
AU - Wojtan, Christopher J
AU - Westermann, Rüdiger
AU - Thuerey, Nils
ID - 1415
IS - 2
JF - Computer Graphics Forum
TI - Narrow band FLIP for liquid simulations
VL - 35
ER -
TY - JOUR
AB - Anisotropic dipole-dipole interactions between ultracold dipolar fermions break the symmetry of the Fermi surface and thereby deform it. Here we demonstrate that such a Fermi surface deformation induces a topological phase transition - the so-called Lifshitz transition - in the regime accessible to present-day experiments. We describe the impact of the Lifshitz transition on observable quantities such as the Fermi surface topology, the density-density correlation function, and the excitation spectrum of the system. The Lifshitz transition in ultracold atoms can be controlled by tuning the dipole orientation and, in contrast to the transition studied in crystalline solids, is completely interaction driven.
AU - Van Loon, Erik
AU - Katsnelson, Mikhail
AU - Chomaz, Lauriane
AU - Lemeshko, Mikhail
ID - 1416
IS - 19
JF - Physical Review B - Condensed Matter and Materials Physics
TI - Interaction-driven Lifshitz transition with dipolar fermions in optical lattices
VL - 93
ER -
TY - JOUR
AB - Plant development mediated by the phytohormone auxin depends on tightly controlled cellular auxin levels at its target tissue that are largely established by intercellular and intracellular auxin transport mediated by PIN auxin transporters. Among the eight members of the Arabidopsis PIN family, PIN6 is the least characterized candidate. In this study we generated functional, fluorescent protein-tagged PIN6 proteins and performed comprehensive analysis of their subcellular localization and also performed a detailed functional characterization of PIN6 and its developmental roles. The localization study of PIN6 revealed a dual localization at the plasma membrane (PM) and endoplasmic reticulum (ER). Transport and metabolic profiling assays in cultured cells and Arabidopsis strongly suggest that PIN6 mediates both auxin transport across the PM and intracellular auxin homeostasis, including the regulation of free auxin and auxin conjugates levels. As evidenced by the loss- and gain-of-function analysis, the complex function of PIN6 in auxin transport and homeostasis is required for auxin distribution during lateral and adventitious root organogenesis and for progression of these developmental processes. These results illustrate a unique position of PIN6 within the family of PIN auxin transporters and further add complexity to the developmentally crucial process of auxin transport.
AU - Simon, Sibu
AU - Skůpa, Petr
AU - Viaene, Tom
AU - Zwiewka, Marta
AU - Tejos, Ricardo
AU - Klíma, Petr
AU - Čarná, Mária
AU - Rolčík, Jakub
AU - De Rycke, Riet
AU - Moreno, Ignacio
AU - Dobrev, Petre
AU - Orellana, Ariel
AU - Zažímalová, Eva
AU - Friml, Jirí
ID - 1417
IS - 1
JF - New Phytologist
TI - PIN6 auxin transporter at endoplasmic reticulum and plasma membrane mediates auxin homeostasis and organogenesis in Arabidopsis
VL - 211
ER -
TY - JOUR
AB - We study the superconducting phase of the Hubbard model using the Gutzwiller variational wave function (GWF) and the recently proposed diagrammatic expansion technique (DE-GWF). The DE-GWF method works on the level of the full GWF and in the thermodynamic limit. Here, we consider a finite-size system to study the accuracy of the results as a function of the system size (which is practically unrestricted). We show that the finite-size scaling used, e.g. in the variational Monte Carlo method can lead to significant, uncontrolled errors. The presented research is the first step towards applying the DE-GWF method in studies of inhomogeneous situations, including systems with impurities, defects, inhomogeneous phases, or disorder.
AU - Tomski, Andrzej
AU - Kaczmarczyk, Jan
ID - 1419
IS - 17
JF - Journal of Physics: Condensed Matter
TI - Gutzwiller wave function for finite systems: Superconductivity in the Hubbard model
VL - 28
ER -
TY - CONF
AB - Hybridization methods enable the analysis of hybrid automata with complex, nonlinear dynamics through a sound abstraction process. Complex dynamics are converted to simpler ones with added noise, and then analysis is done using a reachability method for the simpler dynamics. Several such recent approaches advocate that only "dynamic" hybridization techniquesi.e., those where the dynamics are abstracted on-The-fly during a reachability computation are effective. In this paper, we demonstrate this is not the case, and create static hybridization methods that are more scalable than earlier approaches. The main insight in our approach is that quick, numeric simulations can be used to guide the process, eliminating the need for an exponential number of hybridization domains. Transitions between domains are generally timetriggered, avoiding accumulated error from geometric intersections. We enhance our static technique by combining time-Triggered transitions with occasional space-Triggered transitions, and demonstrate the benefits of the combined approach in what we call mixed-Triggered hybridization. Finally, error modes are inserted to confirm that the reachable states stay within the hybridized regions. The developed techniques can scale to higher dimensions than previous static approaches, while enabling the parallelization of the main performance bottleneck for many dynamic hybridization approaches: The nonlinear optimization required for sound dynamics abstraction. We implement our method as a model transformation pass in the HYST tool, and perform reachability analysis and evaluation using an unmodified version of SpaceEx on nonlinear models with up to six dimensions.
AU - Bak, Stanley
AU - Bogomolov, Sergiy
AU - Henzinger, Thomas A
AU - Johnson, Taylor
AU - Prakash, Pradyot
ID - 1421
TI - Scalable static hybridization methods for analysis of nonlinear systems
ER -
TY - JOUR
AB - We study the time-dependent Bogoliubov–de-Gennes equations for generic translation-invariant fermionic many-body systems. For initial states that are close to thermal equilibrium states at temperatures near the critical temperature, we show that the magnitude of the order parameter stays approximately constant in time and, in particular, does not follow a time-dependent Ginzburg–Landau equation, which is often employed as a phenomenological description and predicts a decay of the order parameter in time. The full non-linear structure of the equations is necessary to understand this behavior.
AU - Frank, Rupert
AU - Hainzl, Christian
AU - Schlein, Benjamin
AU - Seiringer, Robert
ID - 1422
IS - 7
JF - Letters in Mathematical Physics
TI - Incompatibility of time-dependent Bogoliubov–de-Gennes and Ginzburg–Landau equations
VL - 106
ER -
TY - JOUR
AB - Direct reciprocity is a mechanism for the evolution of cooperation based on repeated interactions. When individuals meet repeatedly, they can use conditional strategies to enforce cooperative outcomes that would not be feasible in one-shot social dilemmas. Direct reciprocity requires that individuals keep track of their past interactions and find the right response. However, there are natural bounds on strategic complexity: Humans find it difficult to remember past interactions accurately, especially over long timespans. Given these limitations, it is natural to ask how complex strategies need to be for cooperation to evolve. Here, we study stochastic evolutionary game dynamics in finite populations to systematically compare the evolutionary performance of reactive strategies, which only respond to the co-player's previous move, and memory-one strategies, which take into account the own and the co-player's previous move. In both cases, we compare deterministic strategy and stochastic strategy spaces. For reactive strategies and small costs, we find that stochasticity benefits cooperation, because it allows for generous-tit-for-tat. For memory one strategies and small costs, we find that stochasticity does not increase the propensity for cooperation, because the deterministic rule of win-stay, lose-shift works best. For memory one strategies and large costs, however, stochasticity can augment cooperation.
AU - Baek, Seung
AU - Jeong, Hyeongchai
AU - Hilbe, Christian
AU - Nowak, Martin
ID - 1423
JF - Scientific Reports
TI - Comparing reactive and memory-one strategies of direct reciprocity
VL - 6
ER -
TY - JOUR
AB - Brood parasites exploit their host in order to increase their own fitness. Typically, this results in an arms race between parasite trickery and host defence. Thus, it is puzzling to observe hosts that accept parasitism without any resistance. The ‘mafia’ hypothesis suggests that these hosts accept parasitism to avoid retaliation. Retaliation has been shown to evolve when the hosts condition their response to mafia parasites, who use depredation as a targeted response to rejection. However, it is unclear if acceptance would also emerge when ‘farming’ parasites are present in the population. Farming parasites use depredation to synchronize the timing with the host, destroying mature clutches to force the host to re-nest. Herein, we develop an evolutionary model to analyse the interaction between depredatory parasites and their hosts. We show that coevolutionary cycles between farmers and mafia can still induce host acceptance of brood parasites. However, this equilibrium is unstable and in the long-run the dynamics of this host–parasite interaction exhibits strong oscillations: when farmers are the majority, accepters conditional to mafia (the host will reject first and only accept after retaliation by the parasite) have a higher fitness than unconditional accepters (the host always accepts parasitism). This leads to an increase in mafia parasites’ fitness and in turn induce an optimal environment for accepter hosts.
AU - Chakra, Maria
AU - Hilbe, Christian
AU - Traulsen, Arne
ID - 1426
IS - 5
JF - Royal Society Open Science
TI - Coevolutionary interactions between farmers and mafia induce host acceptance of avian brood parasites
VL - 3
ER -
TY - JOUR
AB - Changes in gene expression are an important mode of evolution; however, the proximate mechanism of these changes is poorly understood. In particular, little is known about the effects of mutations within cis binding sites for transcription factors, or the nature of epistatic interactions between these mutations. Here, we tested the effects of single and double mutants in two cis binding sites involved in the transcriptional regulation of the Escherichia coli araBAD operon, a component of arabinose metabolism, using a synthetic system. This system decouples transcriptional control from any posttranslational effects on fitness, allowing a precise estimate of the effect of single and double mutations, and hence epistasis, on gene expression. We found that epistatic interactions between mutations in the araBAD cis-regulatory element are common, and that the predominant form of epistasis is negative. The magnitude of the interactions depended on whether the mutations are located in the same or in different operator sites. Importantly, these epistatic interactions were dependent on the presence of arabinose, a native inducer of the araBAD operon in vivo, with some interactions changing in sign (e.g., from negative to positive) in its presence. This study thus reveals that mutations in even relatively simple cis-regulatory elements interact in complex ways such that selection on the level of gene expression in one environment might perturb regulation in the other environment in an unpredictable and uncorrelated manner.
AU - Lagator, Mato
AU - Igler, Claudia
AU - Moreno, Anaisa
AU - Guet, Calin C
AU - Bollback, Jonathan P
ID - 1427
IS - 3
JF - Molecular Biology and Evolution
TI - Epistatic interactions in the arabinose cis-regulatory element
VL - 33
ER -
TY - CONF
AB - We report on a mathematically rigorous analysis of the superfluid properties of a Bose- Einstein condensate in the many-body ground state of a one-dimensional model of interacting bosons in a random potential.
AU - Könenberg, Martin
AU - Moser, Thomas
AU - Seiringer, Robert
AU - Yngvason, Jakob
ID - 1428
IS - 1
T2 - Journal of Physics: Conference Series
TI - Superfluidity and BEC in a Model of Interacting Bosons in a Random Potential
VL - 691
ER -
TY - JOUR
AB - Solitons are localized waves formed by a balance of focusing and defocusing effects. These nonlinear waves exist in diverse forms of matter yet exhibit similar properties including stability, periodic recurrence and particle-like trajectories. One important property is soliton fission, a process by which an energetic higher-order soliton breaks apart due to dispersive or nonlinear perturbations. Here we demonstrate through both experiment and theory that nonlinear photocarrier generation can induce soliton fission. Using near-field measurements, we directly observe the nonlinear spatial and temporal evolution of optical pulses in situ in a nanophotonic semiconductor waveguide. We develop an analytic formalism describing the free-carrier dispersion (FCD) perturbation and show the experiment exceeds the minimum threshold by an order of magnitude. We confirm these observations with a numerical nonlinear Schrödinger equation model. These results provide a fundamental explanation and physical scaling of optical pulse evolution in free-carrier media and could enable improved supercontinuum sources in gas based and integrated semiconductor waveguides.
AU - Husko, Chad
AU - Wulf, Matthias
AU - Lefrançois, Simon
AU - Combrié, Sylvain
AU - Lehoucq, Gaëlle
AU - De Rossi, Alfredo
AU - Eggleton, Benjamin
AU - Kuipers, Laurens
ID - 1429
JF - Nature Communications
TI - Free-carrier-induced soliton fission unveiled by in situ measurements in nanophotonic waveguides
VL - 7
ER -
TY - JOUR
AB - The rare socially parasitic butterfly Maculinea alcon occurs in two forms, which are characteristic of hygric or xeric habitats and which exploit different host plants and host ants. The status of these two forms has been the subject of considerable controversy. Populations of the two forms are usually spatially distinct, but at Răscruci in Romania both forms occur on the same site (syntopically). We examined the genetic differentiation between the two forms using eight microsatellite markers, and compared with a nearby hygric site, Şardu. Our results showed that while the two forms are strongly differentiated at Răscruci, it is the xeric form there that is most similar to the hygric form at Şardu, and Bayesian clustering algorithms suggest that these two populations have exchanged genes relatively recently. We found strong evidence for population substructuring, caused by high within host ant nest relatedness, indicating very limited dispersal of most ovipositing females, but not association with particular host ant species. Our results are consistent with the results of larger scale phylogeographic studies that suggest that the two forms represent local ecotypes specialising on different host plants, each with a distinct flowering phenology, providing a temporal rather than spatial barrier to gene flow.
AU - Tartally, András
AU - Kelager, Andreas
AU - Fürst, Matthias
AU - Nash, David
ID - 1431
IS - 3
JF - PeerJ
TI - Host plant use drives genetic differentiation in syntopic populations of Maculinea alcon
VL - 2016
ER -
TY - JOUR
AB - CA3–CA3 recurrent excitatory synapses are thought to play a key role in memory storage and pattern completion. Whether the plasticity properties of these synapses are consistent with their proposed network functions remains unclear. Here, we examine the properties of spike timing-dependent plasticity (STDP) at CA3–CA3 synapses. Low-frequency pairing of excitatory postsynaptic potentials (EPSPs) and action potentials (APs) induces long-term potentiation (LTP), independent of temporal order. The STDP curve is symmetric and broad (half-width ~150 ms). Consistent with these STDP induction properties, AP–EPSP sequences lead to supralinear summation of spine [Ca2+] transients. Furthermore, afterdepolarizations (ADPs) following APs efficiently propagate into dendrites of CA3 pyramidal neurons, and EPSPs summate with dendritic ADPs. In autoassociative network models, storage and recall are more robust with symmetric than with asymmetric STDP rules. Thus, a specialized STDP induction rule allows reliable storage and recall of information in the hippocampal CA3 network.
AU - Mishra, Rajiv Kumar
AU - Kim, Sooyun
AU - Guzmán, José
AU - Jonas, Peter M
ID - 1432
JF - Nature Communications
TI - Symmetric spike timing-dependent plasticity at CA3–CA3 synapses optimizes storage and recall in autoassociative networks
VL - 7
ER -
TY - JOUR
AB - We prove that the system of subordination equations, defining the free additive convolution of two probability measures, is stable away from the edges of the support and blow-up singularities by showing that the recent smoothness condition of Kargin is always satisfied. As an application, we consider the local spectral statistics of the random matrix ensemble A+UBU⁎A+UBU⁎, where U is a Haar distributed random unitary or orthogonal matrix, and A and B are deterministic matrices. In the bulk regime, we prove that the empirical spectral distribution of A+UBU⁎A+UBU⁎ concentrates around the free additive convolution of the spectral distributions of A and B on scales down to N−2/3N−2/3.
AU - Bao, Zhigang
AU - Erdös, László
AU - Schnelli, Kevin
ID - 1434
IS - 3
JF - Journal of Functional Analysis
TI - Local stability of the free additive convolution
VL - 271
ER -
TY - JOUR
AB - ATP released from neurons and astrocytes during neuronal activity or under pathophysiological circumstances is able to influence information flow in neuronal circuits by activation of ionotropic P2X and metabotropic P2Y receptors and subsequent modulation of cellular excitability, synaptic strength, and plasticity. In the present paper we review cellular and network effects of P2Y receptors in the brain. We show that P2Y receptors inhibit the release of neurotransmitters, modulate voltage- and ligand-gated ion channels, and differentially influence the induction of synaptic plasticity in the prefrontal cortex, hippocampus, and cerebellum. The findings discussed here may explain how P2Y1 receptor activation during brain injury, hypoxia, inflammation, schizophrenia, or Alzheimer's disease leads to an impairment of cognitive processes. Hence, it is suggested that the blockade of P2Y1 receptors may have therapeutic potential against cognitive disturbances in these states.
AU - Guzmán, José
AU - Gerevich, Zoltan
ID - 1435
JF - Neural Plasticity
TI - P2Y receptors in synaptic transmission and plasticity: Therapeutic potential in cognitive dysfunction
VL - 2016
ER -
TY - JOUR
AB - We study the time evolution of a system of N spinless fermions in R3 which interact through a pair potential, e.g., the Coulomb potential. We compare the dynamics given by the solution to Schrödinger's equation with the time-dependent Hartree-Fock approximation, and we give an estimate for the accuracy of this approximation in terms of the kinetic energy of the system. This leads, in turn, to bounds in terms of the initial total energy of the system.
AU - Bach, Volker
AU - Breteaux, Sébastien
AU - Petrat, Sören P
AU - Pickl, Peter
AU - Tzaneteas, Tim
ID - 1436
IS - 1
JF - Journal de Mathématiques Pures et Appliquées
TI - Kinetic energy estimates for the accuracy of the time-dependent Hartree-Fock approximation with Coulomb interaction
VL - 105
ER -
TY - CONF
AB - In this paper, we consider termination of probabilistic programs with real-valued variables. The questions concerned are: (a) qualitative ones that ask (i) whether the program terminates with probability 1 (almost-sure termination) and (ii) whether the expected termination time is finite (finite termination); (b) quantitative ones that ask (i) to approximate the expected termination time (expectation problem) and (ii) to compute a bound B such that the probability to terminate after B steps decreases exponentially (concentration problem). To solve these questions, we utilize the notion of ranking supermartingales which is a powerful approach for proving termination of probabilistic programs. In detail, we focus on algorithmic synthesis of linear ranking-supermartingales over affine probabilistic programs (APP's) with both angelic and demonic non-determinism. An important subclass of APP's is LRAPP which is defined as the class of all APP's over which a linear ranking-supermartingale exists. Our main contributions are as follows. Firstly, we show that the membership problem of LRAPP (i) can be decided in polynomial time for APP's with at most demonic non-determinism, and (ii) is NP-hard and in PSPACE for APP's with angelic non-determinism; moreover, the NP-hardness result holds already for APP's without probability and demonic non-determinism. Secondly, we show that the concentration problem over LRAPP can be solved in the same complexity as for the membership problem of LRAPP. Finally, we show that the expectation problem over LRAPP can be solved in 2EXPTIME and is PSPACE-hard even for APP's without probability and non-determinism (i.e., deterministic programs). Our experimental results demonstrate the effectiveness of our approach to answer the qualitative and quantitative questions over APP's with at most demonic non-determinism.
AU - Chatterjee, Krishnendu
AU - Fu, Hongfei
AU - Novotny, Petr
AU - Hasheminezhad, Rouzbeh
ID - 1438
TI - Algorithmic analysis of qualitative and quantitative termination problems for affine probabilistic programs
VL - 20-22
ER -
TY - CONF
AB - Fault-tolerant distributed algorithms play an important role in many critical/high-availability applications. These algorithms are notoriously difficult to implement correctly, due to asynchronous communication and the occurrence of faults, such as the network dropping messages or computers crashing. We introduce PSYNC, a domain specific language based on the Heard-Of model, which views asynchronous faulty systems as synchronous ones with an adversarial environment that simulates asynchrony and faults by dropping messages. We define a runtime system for PSYNC that efficiently executes on asynchronous networks. We formalize the relation between the runtime system and PSYNC in terms of observational refinement. The high-level lockstep abstraction introduced by PSYNC simplifies the design and implementation of fault-tolerant distributed algorithms and enables automated formal verification. We have implemented an embedding of PSYNC in the SCALA programming language with a runtime system for asynchronous networks. We show the applicability of PSYNC by implementing several important fault-tolerant distributed algorithms and we compare the implementation of consensus algorithms in PSYNC against implementations in other languages in terms of code size, runtime efficiency, and verification.
AU - Dragoi, Cezara
AU - Henzinger, Thomas A
AU - Zufferey, Damien
ID - 1439
TI - PSYNC: A partially synchronous language for fault-tolerant distributed algorithms
VL - 20-22
ER -
TY - JOUR
AU - Janovjak, Harald L
ID - 1440
IS - 2
JF - Structure
TI - Light at the end of the protein: Crystal structure of a C-terminal light-sensing domain
VL - 24
ER -
TY - JOUR
AB - Optogenetics and photopharmacology enable the spatio-temporal control of cell and animal behavior by light. Although red light offers deep-tissue penetration and minimal phototoxicity, very few red-light-sensitive optogenetic methods are currently available. We have now developed a red-light-induced homodimerization domain. We first showed that an optimized sensory domain of the cyanobacterial phytochrome 1 can be expressed robustly and without cytotoxicity in human cells. We then applied this domain to induce the dimerization of two receptor tyrosine kinases—the fibroblast growth factor receptor 1 and the neurotrophin receptor trkB. This new optogenetic method was then used to activate the MAPK/ERK pathway non-invasively in mammalian tissue and in multicolor cell-signaling experiments. The light-controlled dimerizer and red-light-activated receptor tyrosine kinases will prove useful to regulate a variety of cellular processes with light. Go deep with red: The sensory domain (S) of the cyanobacterial phytochrome 1 (CPH1) was repurposed to induce the homodimerization of proteins in living cells by red light. By using this domain, light-activated protein kinases were engineered that can be activated orthogonally from many fluorescent proteins and through mammalian tissue. Pr/Pfr=red-/far-red-absorbing state of CPH1.
AU - Gschaider-Reichhart, Eva
AU - Inglés Prieto, Álvaro
AU - Tichy, Alexandra-Madelaine
AU - Mckenzie, Catherine
AU - Janovjak, Harald L
ID - 1441
IS - 21
JF - Angewandte Chemie - International Edition
TI - A phytochrome sensory domain permits receptor activation by red light
VL - 55
ER -
TY - JOUR
AB - The accuracy of interdisciplinarity measurements is directly related to the quality of the underlying bibliographic data. Existing indicators of interdisciplinarity are not capable of reflecting the inaccuracies introduced by incorrect and incomplete records because correct and complete bibliographic data can rarely be obtained. This is the case for the Rao–Stirling index, which cannot handle references that are not categorized into disciplinary fields. We introduce a method that addresses this problem. It extends the Rao–Stirling index to acknowledge missing data by calculating its interval of uncertainty using computational optimization. The evaluation of our method indicates that the uncertainty interval is not only useful for estimating the inaccuracy of interdisciplinarity measurements, but it also delivers slightly more accurate aggregated interdisciplinarity measurements than the Rao–Stirling index.
AU - Calatrava Moreno, Maria
AU - Auzinger, Thomas
AU - Werthner, Hannes
ID - 1446
IS - 1
JF - Scientometrics
TI - On the uncertainty of interdisciplinarity measurements due to incomplete bibliographic data
VL - 107
ER -
TY - JOUR
AB - We develop a new and systematic method for proving entropic Ricci curvature lower bounds for Markov chains on discrete sets. Using different methods, such bounds have recently been obtained in several examples (e.g., 1-dimensional birth and death chains, product chains, Bernoulli–Laplace models, and random transposition models). However, a general method to obtain discrete Ricci bounds had been lacking. Our method covers all of the examples above. In addition we obtain new Ricci curvature bounds for zero-range processes on the complete graph. The method is inspired by recent work of Caputo, Dai Pra and Posta on discrete functional inequalities.
AU - Fathi, Max
AU - Maas, Jan
ID - 1448
IS - 3
JF - The Annals of Applied Probability
TI - Entropic Ricci curvature bounds for discrete interacting systems
VL - 26
ER -
TY - JOUR
AB - The actin cytoskeleton plays important roles in the formation and internalization of endocytic vesicles. In yeast, endocytic vesicles move towards early endosomes along actin cables, however, the molecular machinery regulating interaction between endocytic vesicles and actin cables is poorly understood. The Eps15-like protein Pan1p plays a key role in actin-mediated endocytosis and is negatively regulated by Ark1 and Prk1 kinases. Here we show that pan1 mutated to prevent phosphorylation at all 18 threonines, pan1-18TA, displayed almost the same endocytic defect as ark1Δ prk1Δ cells, and contained abnormal actin concentrations including several endocytic compartments. Early endosomes were highly localized in the actin concentrations and displayed movement along actin cables. The dephosphorylated form of Pan1p also caused stable associations between endocytic vesicles and actin cables, and between endocytic vesicles and endosomes. Thus Pan1 phosphorylation is part of a novel mechanism that regulates endocytic compartment interactions with each other and with actin cables.
AU - Toshima, Junko
AU - Furuya, Eri
AU - Nagano, Makoto
AU - Kanno, Chisa
AU - Sakamoto, Yuta
AU - Ebihara, Masashi
AU - Siekhaus, Daria E
AU - Toshima, Jiro
ID - 1475
IS - February 2016
JF - eLife
TI - Yeast Eps15-like endocytic protein Pan1p regulates the interaction between endocytic vesicles, endosomes and the actin cytoskeleton
VL - 5
ER -
TY - JOUR
AB - The dynamic assembly and disassembly of actin filaments is essential for the formation and transport of vesicles during endocytosis. In yeast, two types of actin structures, namely cortical patches and cytoplasmic cables, play a direct role in endocytosis, but how their interaction is regulated remains unclear. Here, we show that Srv2/CAP, an evolutionarily conserved actin regulator, is required for efficient endocytosis owing to its role in the formation of the actin patches that aid initial vesicle invagination and of the actin cables that these move along. Deletion of the SRV2 gene resulted in the appearance of aberrant fragmented actin cables that frequently moved past actin patches, the sites of endocytosis. We find that the C-terminal CARP domain of Srv2p is vitally important for the proper assembly of actin patches and cables; we also demonstrate that the N-terminal helical folded domain of Srv2 is required for its localization to actin patches, specifically to the ADP-actin rich region through an interaction with cofilin. These results demonstrate the in vivo roles of Srv2p in the regulation of the actin cytoskeleton during clathrin-mediated endocytosis
AU - Toshima, Junko
AU - Horikomi, Chika
AU - Okada, Asuka
AU - Hatori, Makiko
AU - Nagano, Makoto
AU - Masuda, Atsushi
AU - Yamamoto, Wataru
AU - Siekhaus, Daria E
AU - Toshima, Jiro
ID - 1476
IS - 2
JF - Journal of Cell Science
TI - Srv2/CAP is required for polarized actin cable assembly and patch internalization during clathrin-mediated endocytosis
VL - 129
ER -
TY - JOUR
AB - We consider partially observable Markov decision processes (POMDPs) with ω-regular conditions specified as parity objectives. The class of ω-regular languages provides a robust specification language to express properties in verification, and parity objectives are canonical forms to express them. The qualitative analysis problem given a POMDP and a parity objective asks whether there is a strategy to ensure that the objective is satisfied with probability 1 (resp. positive probability). While the qualitative analysis problems are undecidable even for special cases of parity objectives, we establish decidability (with optimal complexity) for POMDPs with all parity objectives under finite-memory strategies. We establish optimal (exponential) memory bounds and EXPTIME-completeness of the qualitative analysis problems under finite-memory strategies for POMDPs with parity objectives. We also present a practical approach, where we design heuristics to deal with the exponential complexity, and have applied our implementation on a number of POMDP examples.
AU - Chatterjee, Krishnendu
AU - Chmelik, Martin
AU - Tracol, Mathieu
ID - 1477
IS - 5
JF - Journal of Computer and System Sciences
TI - What is decidable about partially observable Markov decision processes with ω-regular objectives
VL - 82
ER -
TY - JOUR
AB - We consider the Tonks-Girardeau gas subject to a random external potential. If the disorder is such that the underlying one-particle Hamiltonian displays localization (which is known to be generically the case), we show that there is exponential decay of correlations in the many-body eigenstates. Moreover, there is no Bose-Einstein condensation and no superfluidity, even at zero temperature.
AU - Seiringer, Robert
AU - Warzel, Simone
ID - 1478
IS - 3
JF - New Journal of Physics
TI - Decay of correlations and absence of superfluidity in the disordered Tonks-Girardeau gas
VL - 18
ER -
TY - JOUR
AB - Most entropy notions H(.) like Shannon or min-entropy satisfy a chain rule stating that for random variables X,Z, and A we have H(X|Z,A)≥H(X|Z)−|A|. That is, by conditioning on A the entropy of X can decrease by at most the bitlength |A| of A. Such chain rules are known to hold for some computational entropy notions like Yao’s and unpredictability-entropy. For HILL entropy, the computational analogue of min-entropy, the chain rule is of special interest and has found many applications, including leakage-resilient cryptography, deterministic encryption, and memory delegation. These applications rely on restricted special cases of the chain rule. Whether the chain rule for conditional HILL entropy holds in general was an open problem for which we give a strong negative answer: we construct joint distributions (X,Z,A), where A is a distribution over a single bit, such that the HILL entropy H HILL (X|Z) is large but H HILL (X|Z,A) is basically zero.
Our counterexample just makes the minimal assumption that NP⊈P/poly. Under the stronger assumption that injective one-way function exist, we can make all the distributions efficiently samplable.
Finally, we show that some more sophisticated cryptographic objects like lossy functions can be used to sample a distribution constituting a counterexample to the chain rule making only a single invocation to the underlying object.
AU - Krenn, Stephan
AU - Pietrzak, Krzysztof Z
AU - Wadia, Akshay
AU - Wichs, Daniel
ID - 1479
IS - 3
JF - Computational Complexity
TI - A counterexample to the chain rule for conditional HILL entropy
VL - 25
ER -
TY - JOUR
AB - Exponential varieties arise from exponential families in statistics. These real algebraic varieties have strong positivity and convexity properties, familiar from toric varieties and their moment maps. Among them are varieties of inverses of symmetric matrices satisfying linear constraints. This class includes Gaussian graphical models. We develop a general theory of exponential varieties. These are derived from hyperbolic polynomials and their integral representations. We compare the multidegrees and ML degrees of the gradient map for hyperbolic polynomials.
AU - Michałek, Mateusz
AU - Sturmfels, Bernd
AU - Uhler, Caroline
AU - Zwiernik, Piotr
ID - 1480
IS - 1
JF - Proceedings of the London Mathematical Society
TI - Exponential varieties
VL - 112
ER -
TY - JOUR
AB - Plants have the ability to continously generate new organs by maintaining populations of stem cells throught their lives. The shoot apical meristem (SAM) provides a stable environment for the maintenance of stem cells. All cells inside the SAM divide, yet boundaries and patterns are maintained. Experimental evidence indicates that patterning is independent of cell lineage, thus a dynamic self-regulatory mechanism is required. A pivotal role in the organization of the SAM is played by the WUSCHEL gene (WUS). An important question in this regard is that how WUS expression is positioned in the SAM via a cell-lineage independent signaling mechanism. In this study we demonstrate via mathematical modeling that a combination of an inhibitor of the Cytokinin (CK) receptor, Arabidopsis histidine kinase 4 (AHK4) and two morphogens originating from the top cell layer, can plausibly account for the cell lineage-independent centering of WUS expression within SAM. Furthermore, our laser ablation and microsurgical experiments support the hypothesis that patterning in SAM occurs at the level of CK reception and signaling. The model suggests that the interplay between CK signaling, WUS/CLV feedback loop and boundary signals can account for positioning of the WUS expression, and provides directions for further experimental investigation.
AU - Adibi, Milad
AU - Yoshida, Saiko
AU - Weijers, Dolf
AU - Fleck, Christian
ID - 1482
IS - 2
JF - PLoS One
TI - Centering the organizing center in the Arabidopsis thaliana shoot apical meristem by a combination of cytokinin signaling and self-organization
VL - 11
ER -
TY - JOUR
AU - Chen, Xu
AU - Wu, Shuang
AU - Liu, Zengyu
AU - Friml, Jiřĺ
ID - 1484
IS - 6
JF - Trends in Cell Biology
TI - Environmental and endogenous control of cortical microtubule orientation
VL - 26
ER -
TY - JOUR
AB - In this article the notion of metabolic turnover is revisited in the light of recent results of out-of-equilibrium thermodynamics. By means of Monte Carlo methods we perform an exact sampling of the enzymatic fluxes in a genome scale metabolic network of E. Coli in stationary growth conditions from which we infer the metabolites turnover times. However the latter are inferred from net fluxes, and we argue that this approximation is not valid for enzymes working nearby thermodynamic equilibrium. We recalculate turnover times from total fluxes by performing an energy balance analysis of the network and recurring to the fluctuation theorem. We find in many cases values one of order of magnitude lower, implying a faster picture of intermediate metabolism.
AU - De Martino, Daniele
ID - 1485
IS - 1
JF - Physical Biology
TI - Genome-scale estimate of the metabolic turnover of E. Coli from the energy balance analysis
VL - 13
ER -
TY - JOUR
AB - We review recent results concerning the mathematical properties of the Bardeen-Cooper-Schrieffer (BCS) functional of superconductivity, which were obtained in a series of papers, partly in collaboration with R. Frank, E. Hamza, S. Naboko, and J. P. Solovej. Our discussion includes, in particular, an investigation of the critical temperature for a general class of interaction potentials, as well as a study of its dependence on external fields. We shall explain how the Ginzburg-Landau model can be derived from the BCS theory in a suitable parameter regime.
AU - Hainzl, Christian
AU - Seiringer, Robert
ID - 1486
IS - 2
JF - Journal of Mathematical Physics
TI - The Bardeen–Cooper–Schrieffer functional of superconductivity and its mathematical properties
VL - 57
ER -
TY - JOUR
AB - Rhythms with time scales of multiple cycles per second permeate the mammalian brain, yet neuroscientists are not certain of their functional roles. One leading idea is that coherent oscillation between two brain regions facilitates the exchange of information between them. In rats, the hippocampus and the vibrissal sensorimotor system both are characterized by rhythmic oscillation in the theta range, 5–12 Hz. Previous work has been divided as to whether the two rhythms are independent or coherent. To resolve this question, we acquired three measures from rats—whisker motion, hippocampal local field potential (LFP), and barrel cortex unit firing—during a whisker-mediated texture discrimination task and during control conditions (not engaged in a whisker-mediated memory task). Compared to control conditions, the theta band of hippocampal LFP showed a marked increase in power as the rats approached and then palpated the texture. Phase synchronization between whisking and hippocampal LFP increased by almost 50% during approach and texture palpation. In addition, a greater proportion of barrel cortex neurons showed firing that was phase-locked to hippocampal theta while rats were engaged in the discrimination task. Consistent with a behavioral consequence of phase synchronization, the rats identified the texture more rapidly and with lower error likelihood on trials in which there was an increase in theta-whisking coherence at the moment of texture palpation. These results suggest that coherence between the whisking rhythm, barrel cortex firing, and hippocampal LFP is augmented selectively during epochs in which the rat collects sensory information and that such coherence enhances the efficiency of integration of stimulus information into memory and decision-making centers.
AU - Grion, Natalia
AU - Akrami, Athena
AU - Zuo, Yangfang
AU - Stella, Federico
AU - Diamond, Mathew
ID - 1487
IS - 2
JF - PLoS Biology
TI - Coherence between rat sensorimotor system and hippocampus is enhanced during tactile discrimination
VL - 14
ER -
TY - JOUR
AB - Branching morphogenesis of the epithelial ureteric bud forms the renal collecting duct system and is critical for normal nephron number, while low nephron number is implicated in hypertension and renal disease. Ureteric bud growth and branching requires GDNF signaling from the surrounding mesenchyme to cells at the ureteric bud tips, via the Ret receptor tyrosine kinase and coreceptor Gfrα1; Ret signaling up-regulates transcription factors Etv4 and Etv5, which are also critical for branching. Despite extensive knowledge of the genetic control of these events, it is not understood, at the cellular level, how renal branching morphogenesis is achieved or how Ret signaling influences epithelial cell behaviors to promote this process. Analysis of chimeric embryos previously suggested a role for Ret signaling in promoting cell rearrangements in the nephric duct, but this method was unsuited to study individual cell behaviors during ureteric bud branching. Here, we use Mosaic Analysis with Double Markers (MADM), combined with organ culture and time-lapse imaging, to trace the movements and divisions of individual ureteric bud tip cells. We first examine wild-type clones and then Ret or Etv4 mutant/wild-type clones in which the mutant and wild-type sister cells are differentially and heritably marked by green and red fluorescent proteins. We find that, in normal kidneys, most individual tip cells behave as self-renewing progenitors, some of whose progeny remain at the tips while others populate the growing UB trunks. In Ret or Etv4 MADM clones, the wild-type cells generated at a UB tip are much more likely to remain at, or move to, the new tips during branching and elongation, while their Ret−/− or Etv4−/− sister cells tend to lag behind and contribute only to the trunks. By tracking successive mitoses in a cell lineage, we find that Ret signaling has little effect on proliferation, in contrast to its effects on cell movement. Our results show that Ret/Etv4 signaling promotes directed cell movements in the ureteric bud tips, and suggest a model in which these cell movements mediate branching morphogenesis.
AU - Riccio, Paul
AU - Cebrián, Cristina
AU - Zong, Hui
AU - Hippenmeyer, Simon
AU - Costantini, Frank
ID - 1488
IS - 2
JF - PLoS Biology
TI - Ret and Etv4 promote directed movements of progenitor cells during renal branching morphogenesis
VL - 14
ER -
TY - JOUR
AB - We prove optimal local law, bulk universality and non-trivial decay for the off-diagonal elements of the resolvent for a class of translation invariant Gaussian random matrix ensembles with correlated entries.
AU - Ajanki, Oskari H
AU - Erdös, László
AU - Krüger, Torben H
ID - 1489
IS - 2
JF - Journal of Statistical Physics
TI - Local spectral statistics of Gaussian matrices with correlated entries
VL - 163
ER -
TY - JOUR
AB - To induce adaptive immunity, dendritic cells (DCs) migrate through afferent lymphatic vessels (LVs) to draining lymph nodes (dLNs). This process occurs in several consecutive steps. Upon entry into lymphatic capillaries, DCs first actively crawl into downstream collecting vessels. From there, they are next passively and rapidly transported to the dLN by lymph flow. Here, we describe a role for the chemokine CCL21 in intralymphatic DC crawling. Performing time-lapse imaging in murine skin, we found that blockade of CCL21-but not the absence of lymph flow-completely abolished DC migration from capillaries toward collecting vessels and reduced the ability of intralymphatic DCs to emigrate from skin. Moreover, we found that in vitro low laminar flow established a CCL21 gradient along lymphatic endothelial monolayers, thereby inducing downstream-directed DC migration. These findings reveal a role for intralymphatic CCL21 in promoting DC trafficking to dLNs, through the formation of a flow-induced gradient.
AU - Russo, Erica
AU - Teijeira, Alvaro
AU - Vaahtomeri, Kari
AU - Willrodt, Ann
AU - Bloch, Joël
AU - Nitschké, Maximilian
AU - Santambrogio, Laura
AU - Kerjaschki, Dontscho
AU - Sixt, Michael K
AU - Halin, Cornelia
ID - 1490
IS - 7
JF - Cell Reports
TI - Intralymphatic CCL21 promotes tissue egress of dendritic cells through afferent lymphatic vessels
VL - 14
ER -
TY - JOUR
AB - We study the ground state of a trapped Bose gas, starting from the full many-body Schrödinger Hamiltonian, and derive the non-linear Schrödinger energy functional in the limit of a large particle number, when the interaction potential converges slowly to a Dirac delta function. Our method is based on quantitative estimates on the discrepancy between the full many-body energy and its mean-field approximation using Hartree states. These are proved using finite dimensional localization and a quantitative version of the quantum de Finetti theorem. Our approach covers the case of attractive interactions in the regime of stability. In particular, our main new result is a derivation of the 2D attractive non-linear Schrödinger ground state.
AU - Lewin, Mathieu
AU - Nam, Phan
AU - Rougerie, Nicolas
ID - 1491
IS - 9
JF - Transactions of the American Mathematical Society
TI - The mean-field approximation and the non-linear Schrödinger functional for trapped Bose gases
VL - 368
ER -
TY - JOUR
AB - To sustain a lifelong ability to initiate organs, plants retain pools of undifferentiated cells with a preserved prolif eration capacity. The root pericycle represents a unique tissue with conditional meristematic activity, and its tight control determines initiation of lateral organs. Here we show that the meristematic activity of the pericycle is constrained by the interaction with the adjacent endodermis. Release of these restraints by elimination of endo dermal cells by single-cell ablation triggers the pericycle to re-enter the cell cycle. We found that endodermis removal substitutes for the phytohormone auxin-dependent initiation of the pericycle meristematic activity. However, auxin is indispensable to steer the cell division plane orientation of new organ-defining divisions. We propose a dual, spatiotemporally distinct role for auxin during lateral root initiation. In the endodermis, auxin releases constraints arising from cell-to-cell interactions that compromise the pericycle meristematic activity, whereas, in the pericycle, auxin defines the orientation of the cell division plane to initiate lateral roots.
AU - Marhavy, Peter
AU - Montesinos López, Juan C
AU - Abuzeineh, Anas
AU - Van Damme, Daniël
AU - Vermeer, Joop
AU - Duclercq, Jérôme
AU - Rakusova, Hana
AU - Marhavá, Petra
AU - Friml, Jirí
AU - Geldner, Niko
AU - Benková, Eva
ID - 1492
IS - 4
JF - Genes and Development
TI - Targeted cell elimination reveals an auxin-guided biphasic mode of lateral root initiation
VL - 30
ER -
TY - JOUR
AB - We introduce a new method for deriving the time-dependent Hartree or Hartree-Fock equations as an effective mean-field dynamics from the microscopic Schrödinger equation for fermionic many-particle systems in quantum mechanics. The method is an adaption of the method used in Pickl (Lett. Math. Phys. 97 (2) 151–164 2011) for bosonic systems to fermionic systems. It is based on a Gronwall type estimate for a suitable measure of distance between the microscopic solution and an antisymmetrized product state. We use this method to treat a new mean-field limit for fermions with long-range interactions in a large volume. Some of our results hold for singular attractive or repulsive interactions. We can also treat Coulomb interaction assuming either a mild singularity cutoff or certain regularity conditions on the solutions to the Hartree(-Fock) equations. In the considered limit, the kinetic and interaction energy are of the same order, while the average force is subleading. For some interactions, we prove that the Hartree(-Fock) dynamics is a more accurate approximation than a simpler dynamics that one would expect from the subleading force. With our method we also treat the mean-field limit coupled to a semiclassical limit, which was discussed in the literature before, and we recover some of the previous results. All results hold for initial data close (but not necessarily equal) to antisymmetrized product states and we always provide explicit rates of convergence.
AU - Petrat, Sören P
AU - Pickl, Peter
ID - 1493
IS - 1
JF - Mathematical Physics, Analysis and Geometry
TI - A new method and a new scaling for deriving fermionic mean-field dynamics
VL - 19
ER -
TY - JOUR
AB - Turbulence is one of the most frequently encountered non-equilibrium phenomena in nature, yet characterizing the transition that gives rise to turbulence in basic shear flows has remained an elusive task. Although, in recent studies, critical points marking the onset of sustained turbulence have been determined for several such flows, the physical nature of the transition could not be fully explained. In extensive experimental and computational studies we show for the example of Couette flow that the onset of turbulence is a second-order phase transition and falls into the directed percolation universality class. Consequently, the complex laminar–turbulent patterns distinctive for the onset of turbulence in shear flows result from short-range interactions of turbulent domains and are characterized by universal critical exponents. More generally, our study demonstrates that even high-dimensional systems far from equilibrium such as turbulence exhibit universality at onset and that here the collective dynamics obeys simple rules.
AU - Lemoult, Grégoire M
AU - Shi, Liang
AU - Avila, Kerstin
AU - Jalikop, Shreyas V
AU - Avila, Marc
AU - Hof, Björn
ID - 1494
IS - 3
JF - Nature Physics
TI - Directed percolation phase transition to sustained turbulence in Couette flow
VL - 12
ER -
TY - JOUR
AB - The two-photon 1s2 2s 2p 3P0 1s22s2 1S0 transition in berylliumlike ions is theoretically investigated within a fully relativistic framework and a second-order perturbation theory. We focus our analysis on how electron correlation, as well as the negative-energy spectrum, can affect the forbidden E1M1 decay rate. For this purpose, we include the electronic correlation via an effective local potential and within a single configuration-state model. Due to its experimental interest, evaluations of decay rates are performed for berylliumlike xenon and uranium. We find that the negative-energy contribution can be neglected at the present level of accuracy in the evaluation of the decay rate. On the other hand, if contributions of electronic correlation are not carefully taken into account, it may change the lifetime of the metastable state by up to 20%. By performing a full-relativistic jj-coupling calculation, we found a decrease of the decay rate by two orders of magnitude compared to non-relativistic LS-coupling calculations, for the selected heavy ions.
AU - Amaro, Pedro
AU - Fratini, Filippo
AU - Safari, Laleh
AU - Machado, Jorge
AU - Guerra, Mauro
AU - Indelicato, Paul
AU - Santos, José
ID - 1496
IS - 3
JF - Physical Review A - Atomic, Molecular, and Optical Physics
TI - Relativistic evaluation of the two-photon decay of the metastable 1s22s2p3P0 state in berylliumlike ions with an effective-potential model
VL - 93
ER -
TY - JOUR
AB - Complex I (NADH:ubiquinone oxidoreductase) plays a central role in cellular energy production, coupling electron transfer between NADH and quinone to proton translocation. It is the largest protein assembly of respiratory chains and one of the most elaborate redox membrane proteins known. Bacterial enzyme is about half the size of mitochondrial and thus provides its important "minimal" model. Dysfunction of mitochondrial complex I is implicated in many human neurodegenerative diseases. The L-shaped complex consists of a hydrophilic arm, where electron transfer occurs, and a membrane arm, where proton translocation takes place. We have solved the crystal structures of the hydrophilic domain of complex I from Thermus thermophilus, the membrane domain from Escherichia coli and recently of the intact, entire complex I from T. thermophilus (536. kDa, 16 subunits, 9 iron-sulphur clusters, 64 transmembrane helices). The 95. Å long electron transfer pathway through the enzyme proceeds from the primary electron acceptor flavin mononucleotide through seven conserved Fe-S clusters to the unusual elongated quinone-binding site at the interface with the membrane domain. Four putative proton translocation channels are found in the membrane domain, all linked by the central flexible axis containing charged residues. The redox energy of electron transfer is coupled to proton translocation by the as yet undefined mechanism proposed to involve long-range conformational changes. This article is part of a Special Issue entitled Respiratory complex I, edited by Volker Zickermann and Ulrich Brandt.
AU - Berrisford, John
AU - Baradaran, Rozbeh
AU - Sazanov, Leonid A
ID - 1521
IS - 7
JF - Biochimica et Biophysica Acta - Bioenergetics
TI - Structure of bacterial respiratory complex I
VL - 1857
ER -
TY - JOUR
AB - We classify smooth Brunnian (i.e., unknotted on both components) embeddings (S2 × S1) ⊔ S3 → ℝ6. Any Brunnian embedding (S2 × S1) ⊔ S3 → ℝ6 is isotopic to an explicitly constructed embedding fk,m,n for some integers k, m, n such that m ≡ n (mod 2). Two embeddings fk,m,n and fk′ ,m′,n′ are isotopic if and only if k = k′, m ≡ m′ (mod 2k) and n ≡ n′ (mod 2k). We use Haefliger’s classification of embeddings S3 ⊔ S3 → ℝ6 in our proof. The relation between the embeddings (S2 × S1) ⊔ S3 → ℝ6 and S3 ⊔ S3 → ℝ6 is not trivial, however. For example, we show that there exist embeddings f: (S2 ×S1) ⊔ S3 → ℝ6 and g, g′ : S3 ⊔ S3 → ℝ6 such that the componentwise embedded connected sum f # g is isotopic to f # g′ but g is not isotopic to g′.
AU - Avvakumov, Serhii
ID - 1522
IS - 1
JF - Moscow Mathematical Journal
TI - The classification of certain linked 3-manifolds in 6-space
VL - 16
ER -
TY - JOUR
AB - For random graphs, the containment problem considers the probability that a binomial random graph G(n, p) contains a given graph as a substructure. When asking for the graph as a topological minor, i.e., for a copy of a subdivision of the given graph, it is well known that the (sharp) threshold is at p = 1/n. We consider a natural analogue of this question for higher-dimensional random complexes Xk(n, p), first studied by Cohen, Costa, Farber and Kappeler for k = 2. Improving previous results, we show that p = Θ(1/ √n) is the (coarse) threshold for containing a subdivision of any fixed complete 2-complex. For higher dimensions k > 2, we get that p = O(n−1/k) is an upper bound for the threshold probability of containing a subdivision of a fixed k-dimensional complex.
AU - Gundert, Anna
AU - Wagner, Uli
ID - 1523
IS - 4
JF - Proceedings of the American Mathematical Society
TI - On topological minors in random simplicial complexes
VL - 144
ER -
TY - CONF
AB - When designing genetic circuits, the typical primitives used in major existing modelling formalisms are gene interaction graphs, where edges between genes denote either an activation or inhibition relation. However, when designing experiments, it is important to be precise about the low-level mechanistic details as to how each such relation is implemented. The rule-based modelling language Kappa allows to unambiguously specify mechanistic details such as DNA binding sites, dimerisation of transcription factors, or co-operative interactions. Such a detailed description comes with complexity and computationally costly executions. We propose a general method for automatically transforming a rule-based program, by eliminating intermediate species and adjusting the rate constants accordingly. To the best of our knowledge, we show the first automated reduction of rule-based models based on equilibrium approximations.
Our algorithm is an adaptation of an existing algorithm, which was designed for reducing reaction-based programs; our version of the algorithm scans the rule-based Kappa model in search for those interaction patterns known to be amenable to equilibrium approximations (e.g. Michaelis-Menten scheme). Additional checks are then performed in order to verify if the reduction is meaningful in the context of the full model. The reduced model is efficiently obtained by static inspection over the rule-set. The tool is tested on a detailed rule-based model of a λ-phage switch, which lists 92 rules and 13 agents. The reduced model has 11 rules and 5 agents, and provides a dramatic reduction in simulation time of several orders of magnitude.
AU - Beica, Andreea
AU - Guet, Calin C
AU - Petrov, Tatjana
ID - 1524
TI - Efficient reduction of kappa models by static inspection of the rule-set
VL - 9271
ER -
TY - CONF
AB - We present the first study of robustness of systems that are both timed as well as reactive (I/O). We study the behavior of such timed I/O systems in the presence of uncertain inputs and formalize their robustness using the analytic notion of Lipschitz continuity: a timed I/O system is K-(Lipschitz) robust if the perturbation in its output is at most K times the perturbation in its input. We quantify input and output perturbation using similarity functions over timed words such as the timed version of the Manhattan distance and the Skorokhod distance. We consider two models of timed I/O systems — timed transducers and asynchronous sequential circuits. We show that K-robustness of timed transducers can be decided in polynomial space under certain conditions. For asynchronous sequential circuits, we reduce K-robustness w.r.t. timed Manhattan distances to K-robustness of discrete letter-to-letter transducers and show PSpace-completeness of the problem.
AU - Henzinger, Thomas A
AU - Otop, Jan
AU - Samanta, Roopsha
ID - 1526
TI - Lipschitz robustness of timed I/O systems
VL - 9583
ER -
TY - JOUR
AB - We consider partially observable Markov decision processes (POMDPs) with a set of target states and an integer cost associated with every transition. The optimization objective we study asks to minimize the expected total cost of reaching a state in the target set, while ensuring that the target set is reached almost surely (with probability 1). We show that for integer costs approximating the optimal cost is undecidable. For positive costs, our results are as follows: (i) we establish matching lower and upper bounds for the optimal cost, both double exponential in the POMDP state space size; (ii) we show that the problem of approximating the optimal cost is decidable and present approximation algorithms developing on the existing algorithms for POMDPs with finite-horizon objectives. While the worst-case running time of our algorithm is double exponential, we also present efficient stopping criteria for the algorithm and show experimentally that it performs well in many examples of interest.
AU - Chatterjee, Krishnendu
AU - Chmelik, Martin
AU - Gupta, Raghav
AU - Kanodia, Ayush
ID - 1529
JF - Artificial Intelligence
TI - Optimal cost almost-sure reachability in POMDPs
VL - 234
ER -
TY - JOUR
AB - Feedback loops in biological networks, among others, enable differentiation and cell cycle progression, and increase robustness in signal transduction. In natural networks, feedback loops are often complex and intertwined, making it challenging to identify which loops are mainly responsible for an observed behavior. However, minimal synthetic replicas could allow for such identification. Here, we engineered a synthetic permease-inducer-repressor system in Saccharomyces cerevisiae to analyze if a transport-mediated positive feedback loop could be a core mechanism for the switch-like behavior in the regulation of metabolic gene networks such as the S. cerevisiae GAL system or the Escherichia coli lac operon. We characterized the synthetic circuit using deterministic and stochastic mathematical models. Similar to its natural counterparts, our synthetic system shows bistable and hysteretic behavior, and the inducer concentration range for bistability as well as the switching rates between the two stable states depend on the repressor concentration. Our results indicate that a generic permease–inducer–repressor circuit with a single feedback loop is sufficient to explain the experimentally observed bistable behavior of the natural systems. We anticipate that the approach of reimplementing natural systems with orthogonal parts to identify crucial network components is applicable to other natural systems such as signaling pathways.
AU - Gnügge, Robert
AU - Dharmarajan, Lekshmi
AU - Lang, Moritz
AU - Stelling, Jörg
ID - 1008
IS - 10
JF - ACS Synthetic Biology
TI - An orthogonal permease–inducer–repressor feedback loop shows bistability
VL - 5
ER -
TY - CONF
AB - Experience constantly shapes neural circuits through a variety of plasticity mechanisms. While the functional roles of some plasticity mechanisms are well-understood, it remains unclear how changes in neural excitability contribute to learning. Here, we develop a normative interpretation of intrinsic plasticity (IP) as a key component of unsupervised learning. We introduce a novel generative mixture model that accounts for the class-specific statistics of stimulus intensities, and we derive a neural circuit that learns the input classes and their intensities. We will analytically show that inference and learning for our generative model can be achieved by a neural circuit with intensity-sensitive neurons equipped with a specific form of IP. Numerical experiments verify our analytical derivations and show robust behavior for artificial and natural stimuli. Our results link IP to non-trivial input statistics, in particular the statistics of stimulus intensities for classes to which a neuron is sensitive. More generally, our work paves the way toward new classification algorithms that are robust to intensity variations.
AU - Monk, Travis
AU - Savin, Cristina
AU - Lücke, Jörg
ID - 948
TI - Neurons equipped with intrinsic plasticity learn stimulus intensity statistics
VL - 29
ER -
TY - GEN
AU - Roux, Camille
AU - Fraisse, Christelle
AU - Romiguier, Jonathan
AU - Anciaux, Youann
AU - Galtier, Nicolas
AU - Bierne, Nicolas
ID - 9862
TI - Simulation study to test the robustness of ABC in face of recent times of divergence
ER -
TY - GEN
AU - Roux, Camille
AU - Fraisse, Christelle
AU - Romiguier, Jonathan
AU - Anciaux, Youann
AU - Galtier, Nicolas
AU - Bierne, Nicolas
ID - 9863
TI - Accessions of surveyed individuals, geographic locations and summary statistics
ER -
TY - GEN
AU - Zagórski, Marcin P
AU - Burda, Zdzisław
AU - Wacław, Bartłomiej
ID - 9866
TI - ZIP-archived directory containing all data and computer programs
ER -
TY - GEN
AB - In the beginning of our experiment, subjects were asked to read a few pages on their computer screens that would explain the rules of the subsequent game. Here, we provide these instructions, translated from German.
AU - Hilbe, Christian
AU - Hagel, Kristin
AU - Milinski, Manfred
ID - 9867
TI - Experimental game instructions
ER -
TY - GEN
AB - The raw data file containing the experimental decisions of all our study subjects.
AU - Hilbe, Christian
AU - Hagel, Kristin
AU - Milinski, Manfred
ID - 9868
TI - Experimental data
ER -
TY - GEN
AB - A lower bound on the error of a positional estimator with limited positional information is derived.
AU - Hillenbrand, Patrick
AU - Gerland, Ulrich
AU - Tkačik, Gašper
ID - 9869
TI - Error bound on an estimator of position
ER -
TY - GEN
AB - The effect of noise in the input field on an Ising model is approximated. Furthermore, methods to compute positional information in an Ising model by transfer matrices and Monte Carlo sampling are outlined.
AU - Hillenbrand, Patrick
AU - Gerland, Ulrich
AU - Tkačik, Gašper
ID - 9870
TI - Computation of positional information in an Ising model
ER -
TY - GEN
AB - The positional information in a discrete morphogen field with Gaussian noise is computed.
AU - Hillenbrand, Patrick
AU - Gerland, Ulrich
AU - Tkačik, Gašper
ID - 9871
TI - Computation of positional information in a discrete morphogen field
ER -
TY - GEN
AU - Boehm, Alex
AU - Arnoldini, Markus
AU - Bergmiller, Tobias
AU - Röösli, Thomas
AU - Bigosch, Colette
AU - Ackermann, Martin
ID - 9873
TI - Quantification of the growth rate reduction as a consequence of age-specific mortality
ER -
TY - JOUR
AB - The inference of demographic history from genome data is hindered by a lack of efficient computational approaches. In particular, it has proved difficult to exploit the information contained in the distribution of genealogies across the genome. We have previously shown that the generating function (GF) of genealogies can be used to analytically compute likelihoods of demographic models from configurations of mutations in short sequence blocks (Lohse et al. 2011). Although the GF has a simple, recursive form, the size of such likelihood calculations explodes quickly with the number of individuals and applications of this framework have so far been mainly limited to small samples (pairs and triplets) for which the GF can be written by hand. Here we investigate several strategies for exploiting the inherent symmetries of the coalescent. In particular, we show that the GF of genealogies can be decomposed into a set of equivalence classes that allows likelihood calculations from nontrivial samples. Using this strategy, we automated blockwise likelihood calculations for a general set of demographic scenarios in Mathematica. These histories may involve population size changes, continuous migration, discrete divergence, and admixture between multiple populations. To give a concrete example, we calculate the likelihood for a model of isolation with migration (IM), assuming two diploid samples without phase and outgroup information. We demonstrate the new inference scheme with an analysis of two individual butterfly genomes from the sister species Heliconius melpomene rosina and H. cydno.
AU - Lohse, Konrad
AU - Chmelik, Martin
AU - Martin, Simon
AU - Barton, Nicholas H
ID - 1518
IS - 2
JF - Genetics
TI - Efficient strategies for calculating blockwise likelihoods under the coalescent
VL - 202
ER -
TY - JOUR
AB - Cytokinin is a phytohormone that is well known for its roles in numerous plant growth and developmental processes, yet it has also been linked to abiotic stress response in a less defined manner. Arabidopsis (Arabidopsis thaliana) Cytokinin Response Factor 6 (CRF6) is a cytokinin-responsive AP2/ERF-family transcription factor that, through the cytokinin signaling pathway, plays a key role in the inhibition of dark-induced senescence. CRF6 expression is also induced by oxidative stress, and here we show a novel function for CRF6 in relation to oxidative stress and identify downstream transcriptional targets of CRF6 that are repressed in response to oxidative stress. Analysis of transcriptomic changes in wild-type and crf6 mutant plants treated with H2O2 identified CRF6-dependent differentially expressed transcripts, many of which were repressed rather than induced. Moreover, many repressed genes also show decreased expression in 35S:CRF6 overexpressing plants. Together, these findings suggest that CRF6 functions largely as a transcriptional repressor. Interestingly, among the H2O2 repressed CRF6-dependent transcripts was a set of five genes associated with cytokinin processes: (signaling) ARR6, ARR9, ARR11, (biosynthesis) LOG7, and (transport) ABCG14. We have examined mutants of these cytokinin-associated target genes to reveal novel connections to oxidative stress. Further examination of CRF6-DNA interactions indicated that CRF6 may regulate its targets both directly and indirectly. Together, this shows that CRF6 functions during oxidative stress as a negative regulator to control this cytokinin-associated module of CRF6- dependent genes and establishes a novel connection between cytokinin and oxidative stress response.
AU - Zwack, Paul
AU - De Clercq, Inge
AU - Howton, Timothy
AU - Hallmark, H Tucker
AU - Hurny, Andrej
AU - Keshishian, Erika
AU - Parish, Alyssa
AU - Benková, Eva
AU - Mukhtar, M Shahid
AU - Van Breusegem, Frank
AU - Rashotte, Aaron
ID - 1331
IS - 2
JF - Plant Physiology
SN - 0032-0889
TI - Cytokinin response factor 6 represses cytokinin-associated genes during oxidative stress
VL - 172
ER -
TY - JOUR
AB - We study the homomorphism induced in homology by a closed correspondence between topological spaces, using projections from the graph of the correspondence to its domain and codomain. We provide assumptions under which the homomorphism induced by an outer approximation of a continuous map coincides with the homomorphism induced in homology by the map. In contrast to more classical results we do not require that the projection to the domain have acyclic preimages. Moreover, we show that it is possible to retrieve correct homological information from a correspondence even if some data is missing or perturbed. Finally, we describe an application to combinatorial maps that are either outer approximations of continuous maps or reconstructions of such maps from a finite set of data points.
AU - Harker, Shaun
AU - Kokubu, Hiroshi
AU - Mischaikow, Konstantin
AU - Pilarczyk, Pawel
ID - 1252
IS - 4
JF - Proceedings of the American Mathematical Society
SN - 1088-6826
TI - Inducing a map on homology from a correspondence
VL - 144
ER -
TY - JOUR
AB - Selection, mutation, and random drift affect the dynamics of allele frequencies and consequently of quantitative traits. While the macroscopic dynamics of quantitative traits can be measured, the underlying allele frequencies are typically unobserved. Can we understand how the macroscopic observables evolve without following these microscopic processes? This problem has been studied previously by analogy with statistical mechanics: the allele frequency distribution at each time point is approximated by the stationary form, which maximizes entropy. We explore the limitations of this method when mutation is small (4Nμ < 1) so that populations are typically close to fixation, and we extend the theory in this regime to account for changes in mutation strength. We consider a single diallelic locus either under directional selection or with overdominance and then generalize to multiple unlinked biallelic loci with unequal effects. We find that the maximum-entropy approximation is remarkably accurate, even when mutation and selection change rapidly.
AU - Bod'ová, Katarína
AU - Tkacik, Gasper
AU - Barton, Nicholas H
ID - 1420
IS - 4
JF - Genetics
TI - A general approximation for the dynamics of quantitative traits
VL - 202
ER -
TY - CONF
AB - Games on graphs provide the appropriate framework to study several central problems in computer science, such as verification and synthesis of reactive systems. One of the most basic objectives for games on graphs is the liveness (or Büchi) objective that given a target set of vertices requires that some vertex in the target set is visited infinitely often. We study generalized Büchi objectives (i.e., conjunction of liveness objectives), and implications between two generalized Büchi objectives (known as GR(1) objectives), that arise in numerous applications in computer-aided verification. We present improved algorithms and conditional super-linear lower bounds based on widely believed assumptions about the complexity of (A1) combinatorial Boolean matrix multiplication and (A2) CNF-SAT. We consider graph games with n vertices, m edges, and generalized Büchi objectives with k conjunctions. First, we present an algorithm with running time O(k*n^2), improving the previously known O(k*n*m) and O(k^2*n^2) worst-case bounds. Our algorithm is optimal for dense graphs under (A1). Second, we show that the basic algorithm for the problem is optimal for sparse graphs when the target sets have constant size under (A2). Finally, we consider GR(1) objectives, with k_1 conjunctions in the antecedent and k_2 conjunctions in the consequent, and present an O(k_1 k_2 n^{2.5})-time algorithm, improving the previously known O(k_1*k_2*n*m)-time algorithm for m > n^{1.5}.
AU - Chatterjee, Krishnendu
AU - Dvorák, Wolfgang
AU - Henzinger, Monika H
AU - Loitzenbauer, Veronika
ID - 1068
TI - Conditionally optimal algorithms for generalized Büchi Games
VL - 58
ER -
TY - JOUR
AB - Emerging infectious diseases (EIDs) have contributed significantly to the current biodiversity crisis, leading to widespread epidemics and population loss. Owing to genetic variation in pathogen virulence, a complete understanding of species decline requires the accurate identification and characterization of EIDs. We explore this issue in the Western honeybee, where increasing mortality of populations in the Northern Hemisphere has caused major concern. Specifically, we investigate the importance of genetic identity of the main suspect in mortality, deformed wing virus (DWV), in driving honeybee loss. Using laboratory experiments and a systematic field survey, we demonstrate that an emerging DWV genotype (DWV-B) is more virulent than the established DWV genotype (DWV-A) and is widespread in the landscape. Furthermore, we show in a simple model that colonies infected with DWV-B collapse sooner than colonies infected with DWV-A. We also identify potential for rapid DWV evolution by revealing extensive genome-wide recombination in vivo. The emergence of DWV-B in naive honeybee populations, including via recombination with DWV-A, could be of significant ecological and economic importance. Our findings emphasize that knowledge of pathogen genetic identity and diversity is critical to understanding drivers of species decline.
AU - Mcmahon, Dino
AU - Natsopoulou, Myrsini
AU - Doublet, Vincent
AU - Fürst, Matthias
AU - Weging, Silvio
AU - Brown, Mark
AU - Gogol Döring, Andreas
AU - Paxton, Robert
ID - 1262
IS - 1833
JF - Proceedings of the Royal Society of London Series B Biological Sciences
TI - Elevated virulence of an emerging viral genotype as a driver of honeybee loss
VL - 283
ER -
TY - GEN
AB - Emerging infectious diseases (EIDs) have contributed significantly to the current biodiversity crisis, leading to widespread epidemics and population loss. Owing to genetic variation in pathogen virulence, a complete understanding of species decline requires the accurate identification and characterization of EIDs. We explore this issue in the Western honeybee, where increasing mortality of populations in the Northern Hemisphere has caused major concern. Specifically, we investigate the importance of genetic identity of the main suspect in mortality, deformed wing virus (DWV), in driving honeybee loss. Using laboratory experiments and a systematic field survey, we demonstrate that an emerging DWV genotype (DWV-B) is more virulent than the established DWV genotype (DWV-A) and is widespread in the landscape. Furthermore, we show in a simple model that colonies infected with DWV-B collapse sooner than colonies infected with DWV-A. We also identify potential for rapid DWV evolution by revealing extensive genome-wide recombination in vivo. The emergence of DWV-B in naive honeybee populations, including via recombination with DWV-A, could be of significant ecological and economic importance. Our findings emphasize that knowledge of pathogen genetic identity and diversity is critical to understanding drivers of species decline.
AU - Mcmahon, Dino
AU - Natsopoulou, Myrsini
AU - Doublet, Vincent
AU - Fürst, Matthias
AU - Weging, Silvio
AU - Brown, Mark
AU - Gogol Döring, Andreas
AU - Paxton, Robert
ID - 9704
TI - Data from: Elevated virulence of an emerging viral genotype as a driver of honeybee loss
ER -
TY - JOUR
AB - Across the nervous system, certain population spiking patterns are observed far more frequently than others. A hypothesis about this structure is that these collective activity patterns function as population codewords–collective modes–carrying information distinct from that of any single cell. We investigate this phenomenon in recordings of ∼150 retinal ganglion cells, the retina’s output. We develop a novel statistical model that decomposes the population response into modes; it predicts the distribution of spiking activity in the ganglion cell population with high accuracy. We found that the modes represent localized features of the visual stimulus that are distinct from the features represented by single neurons. Modes form clusters of activity states that are readily discriminated from one another. When we repeated the same visual stimulus, we found that the same mode was robustly elicited. These results suggest that retinal ganglion cells’ collective signaling is endowed with a form of error-correcting code–a principle that may hold in brain areas beyond retina.
AU - Prentice, Jason
AU - Marre, Olivier
AU - Ioffe, Mark
AU - Loback, Adrianna
AU - Tkacik, Gasper
AU - Berry, Michael
ID - 1197
IS - 11
JF - PLoS Computational Biology
TI - Error-robust modes of the retinal population code
VL - 12
ER -
TY - JOUR
AB - Parasitism creates selection for resistance mechanisms in host populations and is hypothesized to promote increased host evolvability. However, the influence of these traits on host evolution when parasites are no longer present is unclear. We used experimental evolution and whole-genome sequencing of Escherichia coli to determine the effects of past and present exposure to parasitic viruses (phages) on the spread of mutator alleles, resistance, and bacterial competitive fitness. We found that mutator alleles spread rapidly during adaptation to any of four different phage species, and this pattern was even more pronounced with multiple phages present simultaneously. However, hypermutability did not detectably accelerate adaptation in the absence of phages and recovery of fitness costs associated with resistance. Several lineages evolved phage resistance through elevated mucoidy, and during subsequent evolution in phage-free conditions they rapidly reverted to nonmucoid, phage-susceptible phenotypes. Genome sequencing revealed that this phenotypic reversion was achieved by additional genetic changes rather than by genotypic reversion of the initial resistance mutations. Insertion sequence (IS) elements played a key role in both the acquisition of resistance and adaptation in the absence of parasites; unlike single nucleotide polymorphisms, IS insertions were not more frequent in mutator lineages. Our results provide a genetic explanation for rapid reversion of mucoidy, a phenotype observed in other bacterial species including human pathogens. Moreover, this demonstrates that the types of genetic change underlying adaptation to fitness costs, and consequently the impact of evolvability mechanisms such as increased point-mutation rates, depend critically on the mechanism of resistance.
AU - Wielgoss, Sébastien
AU - Bergmiller, Tobias
AU - Bischofberger, Anna M.
AU - Hall, Alex R.
ID - 5749
IS - 3
JF - Molecular Biology and Evolution
SN - 0737-4038
TI - Adaptation to parasites and costs of parasite resistance in mutator and nonmutator bacteria
VL - 33
ER -
TY - GEN
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 - 9720
TI - Data from: A sting in the spit: widespread cross-infection of multiple RNA viruses across wild and managed bees
ER -
TY - GEN
AB - Much of quantitative genetics is based on the ‘infinitesimal model’, under which selection has a negligible effect on the genetic variance. This is typically justified by assuming a very large number of loci with additive effects. However, it applies even when genes interact, provided that the number of loci is large enough that selection on each of them is weak relative to random drift. In the long term, directional selection will change allele frequencies, but even then, the effects of epistasis on the ultimate change in trait mean due to selection may be modest. Stabilising selection can maintain many traits close to their optima, even when the underlying alleles are weakly selected. However, the number of traits that can be optimised is apparently limited to ~4Ne by the ‘drift load’, and this is hard to reconcile with the apparent complexity of many organisms. Just as for the mutation load, this limit can be evaded by a particular form of negative epistasis. A more robust limit is set by the variance in reproductive success. This suggests that selection accumulates information most efficiently in the infinitesimal regime, when selection on individual alleles is weak, and comparable with random drift. A review of evidence on selection strength suggests that although most variance in fitness may be because of alleles with large Nes, substantial amounts of adaptation may be because of alleles in the infinitesimal regime, in which epistasis has modest effects.
AU - Barton, Nicholas H
ID - 9710
TI - Data from: How does epistasis influence the response to selection?
ER -
TY - JOUR
AU - Martin, Olivier
AU - Zagórski, Marcin P
ID - 1373
JF - Physics of Life Reviews
TI - Network architectures and operating principles. Reply to comments on "Drivers of structural features in gene regulatory networks: From biophysical constraints to biological function"
VL - 17
ER -
TY - GEN
AB - Viral capsids are structurally constrained by interactions among the amino acids (AAs) of their constituent proteins. Therefore, epistasis is expected to evolve among physically interacting sites and to influence the rates of substitution. To study the evolution of epistasis, we focused on the major structural protein of the ϕX174 phage family by, first, reconstructing the ancestral protein sequences of 18 species using a Bayesian statistical framework. The inferred ancestral reconstruction differed at eight AAs, for a total of 256 possible ancestral haplotypes. For each ancestral haplotype and the extant species, we estimated, in silico, the distribution of free energies and epistasis of the capsid structure. We found that free energy has not significantly increased but epistasis has. We decomposed epistasis up to fifth order and found that higher-order epistasis sometimes compensates pairwise interactions making the free energy seem additive. The dN/dS ratio is low, suggesting strong purifying selection, and that structure is under stabilizing selection. We synthesized phages carrying ancestral haplotypes of the coat protein gene and measured their fitness experimentally. Our findings indicate that stabilizing mutations can have higher fitness, and that fitness optima do not necessarily coincide with energy minima.
AU - Fernandes Redondo, Rodrigo A
AU - de Vladar, Harold
AU - Włodarski, Tomasz
AU - Bollback, Jonathan P
ID - 9864
TI - Data from evolutionary interplay between structure, energy and epistasis in the coat protein of the ϕX174 phage family
ER -
TY - CONF
AB - We present a coherent microwave to telecom signal converter based on the electro-optical effect using a crystalline WGM-resonator coupled to a 3D microwave cavity, achieving high photon conversion efficiency of 0.1% with MHz bandwidth.
AU - Rueda, Alfredo
AU - Sedlmeir, Florian
AU - Collodo, Michele
AU - Vogl, Ulrich
AU - Stiller, Birgit
AU - Schunk, Georg
AU - Strekalov, Dimitry
AU - Marquardt, Christoph
AU - Fink, Johannes M
AU - Painter, Oskar
AU - Leuchs, Gerd
AU - Schwefel, Harald
ID - 1115
TI - Efficient single sideband microwave to optical conversion using a LiNbO₃ WGM-resonator
ER -
TY - CONF
AB - Given a model of a system and an objective, the model-checking question asks whether the model satisfies the objective. We study polynomial-time problems in two classical models, graphs and Markov Decision Processes (MDPs), with respect to several fundamental -regular objectives, e.g., Rabin and Streett objectives. For many of these problems the best-known upper bounds are quadratic or cubic, yet no super-linear lower bounds are known. In this work our contributions are two-fold: First, we present several improved algorithms, and second, we present the first conditional super-linear lower bounds based on widely believed assumptions about the complexity of CNF-SAT and combinatorial Boolean matrix multiplication. A separation result for two models with respect to an objective means a conditional lower bound for one model that is strictly higher than the existing upper bound for the other model, and similarly for two objectives with respect to a model. Our results establish the following separation results: (1) A separation of models (graphs and MDPs) for disjunctive queries of reachability and Büchi objectives. (2) Two kinds of separations of objectives, both for graphs and MDPs, namely, (2a) the separation of dual objectives such as Streett/Rabin objectives, and (2b) the separation of conjunction and disjunction of multiple objectives of the same type such as safety, Büchi, and coBüchi. In summary, our results establish the first model and objective separation results for graphs and MDPs for various classical -regular objectives. Quite strikingly, we establish conditional lower bounds for the disjunction of objectives that are strictly higher than the existing upper bounds for the conjunction of the same objectives. © 2016 ACM.
AU - Chatterjee, Krishnendu
AU - Dvoák, Wolfgang
AU - Henzinger, Monika H
AU - Loitzenbauer, Veronika
ID - 1140
T2 - Proceedings of the 31st Annual ACM/IEEE Symposium on Logic in Computer Science
TI - Model and objective separation with conditional lower bounds: disjunction is harder than conjunction
ER -
TY - JOUR
AB - Most migrating cells extrude their front by the force of actin polymerization. Polymerization requires an initial nucleation step, which is mediated by factors establishing either parallel filaments in the case of filopodia or branched filaments that form the branched lamellipodial network. Branches are considered essential for regular cell motility and are initiated by the Arp2/3 complex, which in turn is activated by nucleation-promoting factors of the WASP and WAVE families. Here we employed rapid amoeboid crawling leukocytes and found that deletion of the WAVE complex eliminated actin branching and thus lamellipodia formation. The cells were left with parallel filaments at the leading edge, which translated, depending on the differentiation status of the cell, into a unipolar pointed cell shape or cells with multiple filopodia. Remarkably, unipolar cells migrated with increased speed and enormous directional persistence, while they were unable to turn towards chemotactic gradients. Cells with multiple filopodia retained chemotactic activity but their migration was progressively impaired with increasing geometrical complexity of the extracellular environment. These findings establish that diversified leading edge protrusions serve as explorative structures while they slow down actual locomotion.
AU - Leithner, Alexander F
AU - Eichner, Alexander
AU - Müller, Jan
AU - Reversat, Anne
AU - Brown, Markus
AU - Schwarz, Jan
AU - Merrin, Jack
AU - De Gorter, David
AU - Schur, Florian
AU - Bayerl, Jonathan
AU - De Vries, Ingrid
AU - Wieser, Stefan
AU - Hauschild, Robert
AU - Lai, Frank
AU - Moser, Markus
AU - Kerjaschki, Dontscho
AU - Rottner, Klemens
AU - Small, Victor
AU - Stradal, Theresia
AU - Sixt, Michael K
ID - 1321
JF - Nature Cell Biology
TI - Diversified actin protrusions promote environmental exploration but are dispensable for locomotion of leukocytes
VL - 18
ER -
TY - JOUR
AB - Autism spectrum disorders (ASD) are a group of genetic disorders often overlapping with other neurological conditions. We previously described abnormalities in the branched-chain amino acid (BCAA) catabolic pathway as a cause of ASD. Here, we show that the solute carrier transporter 7a5 (SLC7A5), a large neutral amino acid transporter localized at the blood brain barrier (BBB), has an essential role in maintaining normal levels of brain BCAAs. In mice, deletion of Slc7a5 from the endothelial cells of the BBB leads to atypical brain amino acid profile, abnormal mRNA translation, and severe neurological abnormalities. Furthermore, we identified several patients with autistic traits and motor delay carrying deleterious homozygous mutations in the SLC7A5 gene. Finally, we demonstrate that BCAA intracerebroventricular administration ameliorates abnormal behaviors in adult mutant mice. Our data elucidate a neurological syndrome defined by SLC7A5 mutations and support an essential role for the BCAA in human brain function.
AU - Tarlungeanu, Dora-Clara
AU - Deliu, Elena
AU - Dotter, Christoph
AU - Kara, Majdi
AU - Janiesch, Philipp
AU - Scalise, Mariafrancesca
AU - Galluccio, Michele
AU - Tesulov, Mateja
AU - Morelli, Emanuela
AU - Sönmez, Fatma
AU - Bilgüvar, Kaya
AU - Ohgaki, Ryuichi
AU - Kanai, Yoshikatsu
AU - Johansen, Anide
AU - Esharif, Seham
AU - Ben Omran, Tawfeg
AU - Topcu, Meral
AU - Schlessinger, Avner
AU - Indiveri, Cesare
AU - Duncan, Kent
AU - Caglayan, Ahmet
AU - Günel, Murat
AU - Gleeson, Joseph
AU - Novarino, Gaia
ID - 1183
IS - 6
JF - Cell
TI - Impaired amino acid transport at the blood brain barrier is a cause of autism spectrum disorder
VL - 167
ER -
TY - JOUR
AB - During metazoan development, the temporal pattern of morphogen signaling is critical for organizing cell fates in space and time. Yet, tools for temporally controlling morphogen signaling within the embryo are still scarce. Here, we developed a photoactivatable Nodal receptor to determine how the temporal pattern of Nodal signaling affects cell fate specification during zebrafish gastrulation. By using this receptor to manipulate the duration of Nodal signaling in vivo by light, we show that extended Nodal signaling within the organizer promotes prechordal plate specification and suppresses endoderm differentiation. Endoderm differentiation is suppressed by extended Nodal signaling inducing expression of the transcriptional repressor goosecoid (gsc) in prechordal plate progenitors, which in turn restrains Nodal signaling from upregulating the endoderm differentiation gene sox17 within these cells. Thus, optogenetic manipulation of Nodal signaling identifies a critical role of Nodal signaling duration for organizer cell fate specification during gastrulation.
AU - Sako, Keisuke
AU - Pradhan, Saurabh
AU - Barone, Vanessa
AU - Inglés Prieto, Álvaro
AU - Mueller, Patrick
AU - Ruprecht, Verena
AU - Capek, Daniel
AU - Galande, Sanjeev
AU - Janovjak, Harald L
AU - Heisenberg, Carl-Philipp J
ID - 1100
IS - 3
JF - Cell Reports
TI - Optogenetic control of nodal signaling reveals a temporal pattern of nodal signaling regulating cell fate specification during gastrulation
VL - 16
ER -
TY - CONF
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 - Goharshady, Amir
AU - Ibsen-Jensen, Rasmus
AU - Pavlogiannis, Andreas
ID - 1437
TI - Algorithms for algebraic path properties in concurrent systems of constant treewidth components
VL - 20-22
ER -
TY - CONF
AB - We consider nondeterministic probabilistic programs with the most basic liveness property of termination. We present efficient methods for termination analysis of nondeterministic probabilistic programs with polynomial guards and assignments. Our approach is through synthesis of polynomial ranking supermartingales, that on one hand significantly generalizes linear ranking supermartingales and on the other hand is a counterpart of polynomial ranking-functions for proving termination of nonprobabilistic programs. The approach synthesizes polynomial ranking-supermartingales through Positivstellensatz's, yielding an efficient method which is not only sound, but also semi-complete over a large subclass of programs. We show experimental results to demonstrate that our approach can handle several classical programs with complex polynomial guards and assignments, and can synthesize efficient quadratic ranking-supermartingales when a linear one does not exist even for simple affine programs.
AU - Chatterjee, Krishnendu
AU - Fu, Hongfei
AU - Goharshady, Amir
ID - 1386
TI - Termination analysis of probabilistic programs through Positivstellensatz's
VL - 9779
ER -
TY - JOUR
AB - Glycoinositolphosphoceramides (GIPCs) are complex sphingolipids present at the plasma membrane of various eukaryotes with the important exception of mammals. In fungi, these glycosphingolipids commonly contain an alpha-mannose residue (Man) linked at position 2 of the inositol. However, several pathogenic fungi additionally synthesize zwitterionic GIPCs carrying an alpha-glucosamine residue (GlcN) at this position. In the human pathogen Aspergillus fumigatus, the GlcNalpha1,2IPC core (where IPC is inositolphosphoceramide) is elongated to Manalpha1,3Manalpha1,6GlcNalpha1,2IPC, which is the most abundant GIPC synthesized by this fungus. In this study, we identified an A. fumigatus N-acetylglucosaminyltransferase, named GntA, and demonstrate its involvement in the initiation of zwitterionic GIPC biosynthesis. Targeted deletion of the gene encoding GntA in A. fumigatus resulted in complete absence of zwitterionic GIPC; a phenotype that could be reverted by episomal expression of GntA in the mutant. The N-acetylhexosaminyltransferase activity of GntA was substantiated by production of N-acetylhexosamine-IPC in the yeast Saccharomyces cerevisiae upon GntA expression. Using an in vitro assay, GntA was furthermore shown to use UDP-N-acetylglucosamine as donor substrate to generate a glycolipid product resistant to saponification and to digestion by phosphatidylinositol-phospholipase C as expected for GlcNAcalpha1,2IPC. Finally, as the enzymes involved in mannosylation of IPC, GntA was localized to the Golgi apparatus, the site of IPC synthesis.
AU - Engel, Jakob
AU - Schmalhorst, Philipp S
AU - Kruger, Anke
AU - Muller, Christina
AU - Buettner, Falk
AU - Routier, Françoise
ID - 802
IS - 12
JF - Glycobiology
TI - Characterization of an N-acetylglucosaminyltransferase involved in Aspergillus fumigatus zwitterionic glycoinositolphosphoceramide biosynthesis
VL - 25
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 -