TY - CONF
AB - Computing an approximation of the reachable states of a hybrid system is a challenge, mainly because overapproximating the solutions of ODEs with a finite number of sets does not scale well. Using template polyhedra can greatly reduce the computational complexity, since it replaces complex operations on sets with a small number of optimization problems. However, the use of templates may make the over-approximation too conservative. Spurious transitions, which are falsely considered reachable, are particularly detrimental to performance and accuracy, and may exacerbate the state explosion problem. In this paper, we examine how spurious transitions can be avoided with minimal computational effort. To this end, detecting spurious transitions is reduced to the well-known problem of showing that two convex sets are disjoint by finding a hyperplane that separates them. We generalize this to owpipes by considering hyperplanes that evolve with time in correspondence to the dynamics of the system. The approach is implemented in the model checker SpaceEx and demonstrated on examples.
AU - Frehse, Goran
AU - Bogomolov, Sergiy
AU - Greitschus, Marius
AU - Strump, Thomas
AU - Podelski, Andreas
ID - 1692
SN - 978-1-4503-3433-4
T2 - Proceedings of the 18th International Conference on Hybrid Systems: Computation and Control
TI - Eliminating spurious transitions in reachability with support functions
ER -
TY - JOUR
AB - Quantum interference between energetically close states is theoretically investigated, with the state structure being observed via laser spectroscopy. In this work, we focus on hyperfine states of selected hydrogenic muonic isotopes, and on how quantum interference affects the measured Lamb shift. The process of photon excitation and subsequent photon decay is implemented within the framework of nonrelativistic second-order perturbation theory. Due to its experimental interest, calculations are performed for muonic hydrogen, deuterium, and helium-3. We restrict our analysis to the case of photon scattering by incident linear polarized photons and the polarization of the scattered photons not being observed. We conclude that while quantum interference effects can be safely neglected in muonic hydrogen and helium-3, in the case of muonic deuterium there are resonances with close proximity, where quantum interference effects can induce shifts up to a few percent of the linewidth, assuming a pointlike detector. However, by taking into account the geometry of the setup used by the CREMA collaboration, this effect is reduced to less than 0.2% of the linewidth in all possible cases, which makes it irrelevant at the present level of accuracy. © 2015 American Physical Society.
AU - Amaro, Pedro
AU - Franke, Beatrice
AU - Krauth, Julian
AU - Diepold, Marc
AU - Fratini, Filippo
AU - Safari, Laleh
AU - Machado, Jorge
AU - Antognini, Aldo
AU - Kottmann, Franz
AU - Indelicato, Paul
AU - Pohl, Randolf
AU - Santos, José
ID - 1693
IS - 2
JF - Physical Review A
TI - Quantum interference effects in laser spectroscopy of muonic hydrogen, deuterium, and helium-3
VL - 92
ER -
TY - JOUR
AB -
We introduce quantitative timed refinement and timed simulation (directed) metrics, incorporating zenoness checks, for timed systems. These metrics assign positive real numbers which quantify the timing mismatches between two timed systems, amongst non-zeno runs. We quantify timing mismatches in three ways: (1) the maximal timing mismatch that can arise, (2) the “steady-state” maximal timing mismatches, where initial transient timing mismatches are ignored; and (3) the (long-run) average timing mismatches amongst two systems. These three kinds of mismatches constitute three important types of timing differences. Our event times are the global times, measured from the start of the system execution, not just the time durations of individual steps. We present algorithms over timed automata for computing the three quantitative simulation distances to within any desired degree of accuracy. In order to compute the values of the quantitative simulation distances, we use a game theoretic formulation. We introduce two new kinds of objectives for two player games on finite-state game graphs: (1) eventual debit-sum level objectives, and (2) average debit-sum level objectives. We present algorithms for computing the optimal values for these objectives in graph games, and then use these algorithms to compute the values of the timed simulation distances over timed automata.
AU - Chatterjee, Krishnendu
AU - Prabhu, Vinayak
ID - 1694
IS - 9
JF - IEEE Transactions on Automatic Control
TI - Quantitative temporal simulation and refinement distances for timed systems
VL - 60
ER -
TY - JOUR
AB - We give a comprehensive introduction into a diagrammatic method that allows for the evaluation of Gutzwiller wave functions in finite spatial dimensions. We discuss in detail some numerical schemes that turned out to be useful in the real-space evaluation of the diagrams. The method is applied to the problem of d-wave superconductivity in a two-dimensional single-band Hubbard model. Here, we discuss in particular the role of long-range contributions in our diagrammatic expansion. We further reconsider our previous analysis on the kinetic energy gain in the superconducting state.
AU - Kaczmarczyk, Jan
AU - Schickling, Tobias
AU - Bünemann, Jörg
ID - 1695
IS - 9
JF - Physica Status Solidi (B): Basic Solid State Physics
TI - Evaluation techniques for Gutzwiller wave functions in finite dimensions
VL - 252
ER -
TY - JOUR
AB - The recently proposed diagrammatic expansion (DE) technique for the full Gutzwiller wave function (GWF) is applied to the Anderson lattice model. This approach allows for a systematic evaluation of the expectation values with full Gutzwiller wave function in finite-dimensional systems. It introduces results extending in an essential manner those obtained by means of the standard Gutzwiller approximation (GA), which is variationally exact only in infinite dimensions. Within the DE-GWF approach we discuss the principal paramagnetic properties and their relevance to heavy-fermion systems. We demonstrate the formation of an effective, narrow f band originating from atomic f-electron states and subsequently interpret this behavior as a direct itineracy of f electrons; it represents a combined effect of both the hybridization and the correlations induced by the Coulomb repulsive interaction. Such a feature is absent on the level of GA, which is equivalent to the zeroth order of our expansion. Formation of the hybridization- and electron-concentration-dependent narrow f band rationalizes the common assumption of such dispersion of f levels in the phenomenological modeling of the band structure of CeCoIn5. Moreover, it is shown that the emerging f-electron direct itineracy leads in a natural manner to three physically distinct regimes within a single model that are frequently discussed for 4f- or 5f-electron compounds as separate model situations. We identify these regimes as (i) the mixed-valence regime, (ii) Kondo/almost-Kondo insulating regime, and (iii) the Kondo-lattice limit when the f-electron occupancy is very close to the f-state half filling, ⟨nˆf⟩→1. The nonstandard features of the emerging correlated quantum liquid state are stressed.
AU - Wysokiński, Marcin
AU - Kaczmarczyk, Jan
AU - Spałek, Jozef
ID - 1696
IS - 12
JF - Physical Review B
TI - Gutzwiller wave function solution for Anderson lattice model: Emerging universal regimes of heavy quasiparticle states
VL - 92
ER -
TY - JOUR
AB - Motion tracking is a challenge the visual system has to solve by reading out the retinal population. It is still unclear how the information from different neurons can be combined together to estimate the position of an object. Here we recorded a large population of ganglion cells in a dense patch of salamander and guinea pig retinas while displaying a bar moving diffusively. We show that the bar’s position can be reconstructed from retinal activity with a precision in the hyperacuity regime using a linear decoder acting on 100+ cells. We then took advantage of this unprecedented precision to explore the spatial structure of the retina’s population code. The classical view would have suggested that the firing rates of the cells form a moving hill of activity tracking the bar’s position. Instead, we found that most ganglion cells in the salamander fired sparsely and idiosyncratically, so that their neural image did not track the bar. Furthermore, ganglion cell activity spanned an area much larger than predicted by their receptive fields, with cells coding for motion far in their surround. As a result, population redundancy was high, and we could find multiple, disjoint subsets of neurons that encoded the trajectory with high precision. This organization allows for diverse collections of ganglion cells to represent high-accuracy motion information in a form easily read out by downstream neural circuits.
AU - Marre, Olivier
AU - Botella Soler, Vicente
AU - Simmons, Kristina
AU - Mora, Thierry
AU - Tkacik, Gasper
AU - Berry, Michael
ID - 1697
IS - 7
JF - PLoS Computational Biology
TI - High accuracy decoding of dynamical motion from a large retinal population
VL - 11
ER -
TY - JOUR
AB - In mean-payoff games, the objective of the protagonist is to ensure that the limit average of an infinite sequence of numeric weights is nonnegative. In energy games, the objective is to ensure that the running sum of weights is always nonnegative. Multi-mean-payoff and multi-energy games replace individual weights by tuples, and the limit average (resp., running sum) of each coordinate must be (resp., remain) nonnegative. We prove finite-memory determinacy of multi-energy games and show inter-reducibility of multi-mean-payoff and multi-energy games for finite-memory strategies. We improve the computational complexity for solving both classes with finite-memory strategies: we prove coNP-completeness improving the previous known EXPSPACE bound. For memoryless strategies, we show that deciding the existence of a winning strategy for the protagonist is NP-complete. We present the first solution of multi-mean-payoff games with infinite-memory strategies: we show that mean-payoff-sup objectives can be decided in NP∩coNP, whereas mean-payoff-inf objectives are coNP-complete.
AU - Velner, Yaron
AU - Chatterjee, Krishnendu
AU - Doyen, Laurent
AU - Henzinger, Thomas A
AU - Rabinovich, Alexander
AU - Raskin, Jean
ID - 1698
IS - 4
JF - Information and Computation
TI - The complexity of multi-mean-payoff and multi-energy games
VL - 241
ER -
TY - JOUR
AB - By hybridization and backcrossing, alleles can surmount species boundaries and be incorporated into the genome of a related species. This introgression of genes is of particular evolutionary relevance if it involves the transfer of adaptations between populations. However, any beneficial allele will typically be associated with other alien alleles that are often deleterious and hamper the introgression process. In order to describe the introgression of an adaptive allele, we set up a stochastic model with an explicit genetic makeup of linked and unlinked deleterious alleles. Based on the theory of reducible multitype branching processes, we derive a recursive expression for the establishment probability of the beneficial allele after a single hybridization event. We furthermore study the probability that slightly deleterious alleles hitchhike to fixation. The key to the analysis is a split of the process into a stochastic phase in which the advantageous alleles establishes and a deterministic phase in which it sweeps to fixation. We thereafter apply the theory to a set of biologically relevant scenarios such as introgression in the presence of many unlinked or few closely linked deleterious alleles. A comparison to computer simulations shows that the approximations work well over a large parameter range.
AU - Uecker, Hildegard
AU - Setter, Derek
AU - Hermisson, Joachim
ID - 1699
IS - 7
JF - Journal of Mathematical Biology
TI - Adaptive gene introgression after secondary contact
VL - 70
ER -
TY - JOUR
AB - We use the dual boson approach to reveal the phase diagram of the Fermi-Hubbard model with long-range dipole-dipole interactions. By using a large-scale finite-temperature calculation on a 64×64 square lattice we demonstrate the existence of a novel phase, possessing an "ultralong-range" order. The fingerprint of this phase - the density correlation function - features a nontrivial behavior on a scale of tens of lattice sites. We study the properties and the stability of the ultralong-range-ordered phase, and show that it is accessible in modern experiments with ultracold polar molecules and magnetic atoms.
AU - Van Loon, Erik
AU - Katsnelson, Mikhail
AU - Lemeshko, Mikhail
ID - 1700
IS - 8
JF - Physical Review B
TI - Ultralong-range order in the Fermi-Hubbard model with long-range interactions
VL - 92
ER -
TY - JOUR
AB - The activity of a neural network is defined by patterns of spiking and silence from the individual neurons. Because spikes are (relatively) sparse, patterns of activity with increasing numbers of spikes are less probable, but, with more spikes, the number of possible patterns increases. This tradeoff between probability and numerosity is mathematically equivalent to the relationship between entropy and energy in statistical physics. We construct this relationship for populations of up to N = 160 neurons in a small patch of the vertebrate retina, using a combination of direct and model-based analyses of experiments on the response of this network to naturalistic movies. We see signs of a thermodynamic limit, where the entropy per neuron approaches a smooth function of the energy per neuron as N increases. The form of this function corresponds to the distribution of activity being poised near an unusual kind of critical point. We suggest further tests of criticality, and give a brief discussion of its functional significance.
AU - Tkacik, Gasper
AU - Mora, Thierry
AU - Marre, Olivier
AU - Amodei, Dario
AU - Palmer, Stephanie
AU - Berry Ii, Michael
AU - Bialek, William
ID - 1701
IS - 37
JF - PNAS
TI - Thermodynamics and signatures of criticality in a network of neurons
VL - 112
ER -
TY - JOUR
AB - Vegetation clearing and land-use change have depleted many natural plant communities to the point where restoration is required. A major impediment to the success of rebuilding complex vegetation communities is having regular access to sufficient quantities of high-quality seed. Seed-production areas (SPAs) can help generate this seed, but these must be underpinned by a broad genetic base to maximise the evolutionary potential of restored populations. However, genetic bottlenecks can occur at the collection, establishment and production stages in SPAs, requiring genetic evaluation. This is especially relevant for species that may take many years before a return on SPA investment is realised. Two recently established yellow box (Eucalyptus melliodora A.Cunn. ex Schauer, Myrtaceae) SPAs were evaluated to determine whether genetic bottlenecks had occurred between seed collection and SPA establishment. No evidence was found to suggest that a significant loss of genetic diversity had occurred at this stage, although there was a significant difference in diversity between the two SPAs. Complex population genetic structure was also observed in the seed used to source the SPAs, with up to eight groups identified. Plant survival in the SPAs was influenced by seed collection location but not by SPA location and was not associated with genetic diversity. There were also no associations between genetic diversity and plant growth. These data highlighted the importance of chance events when establishing SPAs and indicated that the two yellow box SPAs are likely to provide genetically diverse seed sources for future restoration projects, especially by pooling seed from both SPAs.
AU - Broadhurst, Linda
AU - Fifield, Graham
AU - Vanzella, Bindi
AU - Pickup, Melinda
ID - 1703
IS - 5
JF - Australian Journal of Botany
TI - An evaluation of the genetic structure of seed sources and the maintenance of genetic diversity during establishment of two yellow box (Eucalyptus melliodora) seed-production areas
VL - 63
ER -
TY - JOUR
AB - Given a convex function (Formula presented.) and two hermitian matrices A and B, Lewin and Sabin study in (Lett Math Phys 104:691–705, 2014) the relative entropy defined by (Formula presented.). Among other things, they prove that the so-defined quantity is monotone if and only if (Formula presented.) is operator monotone. The monotonicity is then used to properly define (Formula presented.) for bounded self-adjoint operators acting on an infinite-dimensional Hilbert space by a limiting procedure. More precisely, for an increasing sequence of finite-dimensional projections (Formula presented.) with (Formula presented.) strongly, the limit (Formula presented.) is shown to exist and to be independent of the sequence of projections (Formula presented.). The question whether this sequence converges to its "obvious" limit, namely (Formula presented.), has been left open. We answer this question in principle affirmatively and show that (Formula presented.). If the operators A and B are regular enough, that is (A − B), (Formula presented.) and (Formula presented.) are trace-class, the identity (Formula presented.) holds.
AU - Deuchert, Andreas
AU - Hainzl, Christian
AU - Seiringer, Robert
ID - 1704
IS - 10
JF - Letters in Mathematical Physics
TI - Note on a family of monotone quantum relative entropies
VL - 105
ER -
TY - CONF
AB - We consider a problem of learning kernels for use in SVM classification in the multi-task and lifelong scenarios and provide generalization bounds on the error of a large margin classifier. Our results show that, under mild conditions on the family of kernels used for learning, solving several related tasks simultaneously is beneficial over single task learning. In particular, as the number of observed tasks grows, assuming that in the considered family of kernels there exists one that yields low approximation error on all tasks, the overhead associated with learning such a kernel vanishes and the complexity converges to that of learning when this good kernel is given to the learner.
AU - Pentina, Anastasia
AU - Ben David, Shai
ID - 1706
TI - Multi-task and lifelong learning of kernels
VL - 9355
ER -
TY - JOUR
AB - The competition for resources among cells, individuals or species is a fundamental characteristic of evolution. Biological all-pay auctions have been used to model situations where multiple individuals compete for a single resource. However, in many situations multiple resources with various values exist and single reward auctions are not applicable. We generalize the model to multiple rewards and study the evolution of strategies. In biological all-pay auctions the bid of an individual corresponds to its strategy and is equivalent to its payment in the auction. The decreasingly ordered rewards are distributed according to the decreasingly ordered bids of the participating individuals. The reproductive success of an individual is proportional to its fitness given by the sum of the rewards won minus its payments. Hence, successful bidding strategies spread in the population. We find that the results for the multiple reward case are very different from the single reward case. While the mixed strategy equilibrium in the single reward case with more than two players consists of mostly low-bidding individuals, we show that the equilibrium can convert to many high-bidding individuals and a few low-bidding individuals in the multiple reward case. Some reward values lead to a specialization among the individuals where one subpopulation competes for the rewards and the other subpopulation largely avoids costly competitions. Whether the mixed strategy equilibrium is an evolutionarily stable strategy (ESS) depends on the specific values of the rewards.
AU - Reiter, Johannes
AU - Kanodia, Ayush
AU - Gupta, Raghav
AU - Nowak, Martin
AU - Chatterjee, Krishnendu
ID - 1709
IS - 1812
JF - Proceedings of the Royal Society of London Series B Biological Sciences
TI - Biological auctions with multiple rewards
VL - 282
ER -
TY - JOUR
AB - We consider the hollow on the half-plane {(x, y) : y ≤ 0} ⊂ ℝ2 defined by a function u : (-1, 1) → ℝ, u(x) < 0, and a vertical flow of point particles incident on the hollow. It is assumed that u satisfies the so-called single impact condition (SIC): each incident particle is elastically reflected by graph(u) and goes away without hitting the graph of u anymore. We solve the problem: find the function u minimizing the force of resistance created by the flow. We show that the graph of the minimizer is formed by two arcs of parabolas symmetric to each other with respect to the y-axis. Assuming that the resistance of u ≡ 0 equals 1, we show that the minimal resistance equals π/2 - 2arctan(1/2) ≈ 0.6435. This result completes the previously obtained result [SIAM J. Math. Anal., 46 (2014), pp. 2730-2742] stating in particular that the minimal resistance of a hollow in higher dimensions equals 0.5. We additionally consider a similar problem of minimal resistance, where the hollow in the half-space {(x1,...,xd,y) : y ≤ 0} ⊂ ℝd+1 is defined by a radial function U satisfying the SIC, U(x) = u(|x|), with x = (x1,...,xd), u(ξ) < 0 for 0 ≤ ξ < 1, and u(ξ) = 0 for ξ ≥ 1, and the flow is parallel to the y-axis. The minimal resistance is greater than 0.5 (and coincides with 0.6435 when d = 1) and converges to 0.5 as d → ∞.
AU - Akopyan, Arseniy
AU - Plakhov, Alexander
ID - 1710
IS - 4
JF - Society for Industrial and Applied Mathematics
TI - Minimal resistance of curves under the single impact assumption
VL - 47
ER -
TY - JOUR
AB - The majority of immune cells in Drosophila melanogaster are plasmatocytes; they carry out similar functions to vertebrate macrophages, influencing development as well as protecting against infection and cancer. Plasmatocytes, sometimes referred to with the broader term of hemocytes, migrate widely during embryonic development and cycle in the larvae between sessile and circulating positions. Here we discuss the similarities of plasmatocyte developmental migration and its functions to that of vertebrate macrophages, considering the recent controversy regarding the functions of Drosophila PDGF/VEGF related ligands. We also examine recent findings on the significance of adhesion for plasmatocyte migration in the embryo, as well as proliferation, trans-differentiation, and tumor responses in the larva. We spotlight parallels throughout to vertebrate immune responses.
AU - Ratheesh, Aparna
AU - Belyaeva, Vera
AU - Siekhaus, Daria E
ID - 1712
IS - 10
JF - Current Opinion in Cell Biology
TI - Drosophila immune cell migration and adhesion during embryonic development and larval immune responses
VL - 36
ER -
TY - CONF
AB - We present a flexible framework for the automated competitive analysis of on-line scheduling algorithms for firm-deadline real-time tasks based on multi-objective graphs: Given a task set and an on-line scheduling algorithm specified as a labeled transition system, along with some optional safety, liveness, and/or limit-average constraints for the adversary, we automatically compute the competitive ratio of the algorithm w.r.t. A clairvoyant scheduler. We demonstrate the flexibility and power of our approach by comparing the competitive ratio of several on-line algorithms, including Dover, that have been proposed in the past, for various task sets. Our experimental results reveal that none of these algorithms is universally optimal, in the sense that there are task sets where other schedulers provide better performance. Our framework is hence a very useful design tool for selecting optimal algorithms for a given application.
AU - Chatterjee, Krishnendu
AU - Pavlogiannis, Andreas
AU - Kößler, Alexander
AU - Schmid, Ulrich
ID - 1714
IS - January
T2 - Real-Time Systems Symposium
TI - A framework for automated competitive analysis of on-line scheduling of firm-deadline tasks
VL - 2015
ER -
TY - JOUR
AB - In the vertebrate neural tube, the morphogen Sonic Hedgehog (Shh) establishes a characteristic pattern of gene expression. Here we quantify the Shh gradient in the developing mouse neural tube and show that while the amplitude of the gradient increases over time, the activity of the pathway transcriptional effectors, Gli proteins, initially increases but later decreases. Computational analysis of the pathway suggests three mechanisms that could contribute to this adaptation: transcriptional upregulation of the inhibitory receptor Ptch1, transcriptional downregulation of Gli and the differential stability of active and inactive Gli isoforms. Consistent with this, Gli2 protein expression is downregulated during neural tube patterning and adaptation continues when the pathway is stimulated downstream of Ptch1. Moreover, the Shh-induced upregulation of Gli2 transcription prevents Gli activity levels from adapting in a different cell type, NIH3T3 fibroblasts, despite the upregulation of Ptch1. Multiple mechanisms therefore contribute to the intracellular dynamics of Shh signalling, resulting in different signalling dynamics in different cell types.
AU - Cohen, Michael H
AU - Anna Kicheva
AU - Ribeiro, Ana C
AU - Blassberg, Robert A
AU - Page, Karen M
AU - Barnes, Chris P
AU - Briscoe, James
ID - 1728
JF - Nature Communications
TI - Ptch1 and Gli regulate Shh signalling dynamics via multiple mechanisms
VL - 6
ER -
TY - CONF
AB - We present a computer-aided programming approach to concurrency. The approach allows programmers to program assuming a friendly, non-preemptive scheduler, and our synthesis procedure inserts synchronization to ensure that the final program works even with a preemptive scheduler. The correctness specification is implicit, inferred from the non-preemptive behavior. Let us consider sequences of calls that the program makes to an external interface. The specification requires that any such sequence produced under a preemptive scheduler should be included in the set of such sequences produced under a non-preemptive scheduler. The solution is based on a finitary abstraction, an algorithm for bounded language inclusion modulo an independence relation, and rules for inserting synchronization. We apply the approach to device-driver programming, where the driver threads call the software interface of the device and the API provided by the operating system. Our experiments demonstrate that our synthesis method is precise and efficient, and, since it does not require explicit specifications, is more practical than the conventional approach based on user-provided assertions.
AU - Cerny, Pavol
AU - Clarke, Edmund
AU - Henzinger, Thomas A
AU - Radhakrishna, Arjun
AU - Ryzhyk, Leonid
AU - Samanta, Roopsha
AU - Tarrach, Thorsten
ID - 1729
TI - From non-preemptive to preemptive scheduling using synchronization synthesis
VL - 9207
ER -
TY - JOUR
AB - How much cutting is needed to simplify the topology of a surface? We provide bounds for several instances of this question, for the minimum length of topologically non-trivial closed curves, pants decompositions, and cut graphs with a given combinatorial map in triangulated combinatorial surfaces (or their dual cross-metric counterpart). Our work builds upon Riemannian systolic inequalities, which bound the minimum length of non-trivial closed curves in terms of the genus and the area of the surface. We first describe a systematic way to translate Riemannian systolic inequalities to a discrete setting, and vice-versa. This implies a conjecture by Przytycka and Przytycki (Graph structure theory. Contemporary Mathematics, vol. 147, 1993), a number of new systolic inequalities in the discrete setting, and the fact that a theorem of Hutchinson on the edge-width of triangulated surfaces and Gromov’s systolic inequality for surfaces are essentially equivalent. We also discuss how these proofs generalize to higher dimensions. Then we focus on topological decompositions of surfaces. Relying on ideas of Buser, we prove the existence of pants decompositions of length O(g^(3/2)n^(1/2)) for any triangulated combinatorial surface of genus g with n triangles, and describe an O(gn)-time algorithm to compute such a decomposition. Finally, we consider the problem of embedding a cut graph (or more generally a cellular graph) with a given combinatorial map on a given surface. Using random triangulations, we prove (essentially) that, for any choice of a combinatorial map, there are some surfaces on which any cellular embedding with that combinatorial map has length superlinear in the number of triangles of the triangulated combinatorial surface. There is also a similar result for graphs embedded on polyhedral triangulations.
AU - Colin De Verdière, Éric
AU - Hubard, Alfredo
AU - De Mesmay, Arnaud N
ID - 1730
IS - 3
JF - Discrete & Computational Geometry
TI - Discrete systolic inequalities and decompositions of triangulated surfaces
VL - 53
ER -
TY - JOUR
AB - We consider two-player zero-sum games on graphs. These games can be classified on the basis of the information of the players and on the mode of interaction between them. On the basis of information the classification is as follows: (a) partial-observation (both players have partial view of the game); (b) one-sided complete-observation (one player has complete observation); and (c) complete-observation (both players have complete view of the game). On the basis of mode of interaction we have the following classification: (a) concurrent (both players interact simultaneously); and (b) turn-based (both players interact in turn). The two sources of randomness in these games are randomness in transition function and randomness in strategies. In general, randomized strategies are more powerful than deterministic strategies, and randomness in transitions gives more general classes of games. In this work we present a complete characterization for the classes of games where randomness is not helpful in: (a) the transition function probabilistic transition can be simulated by deterministic transition); and (b) strategies (pure strategies are as powerful as randomized strategies). As consequence of our characterization we obtain new undecidability results for these games.
AU - Chatterjee, Krishnendu
AU - Doyen, Laurent
AU - Gimbert, Hugo
AU - Henzinger, Thomas A
ID - 1731
IS - 12
JF - Information and Computation
TI - Randomness for free
VL - 245
ER -
TY - CONF
AB - We consider partially observable Markov decision processes (POMDPs), that are a standard framework for robotics applications to model uncertainties present in the real world, with temporal logic specifications. All temporal logic specifications in linear-time temporal logic (LTL) can be expressed as parity objectives. We study the qualitative analysis problem for POMDPs with parity objectives that asks whether there is a controller (policy) to ensure that the objective holds with probability 1 (almost-surely). While the qualitative analysis of POMDPs with parity objectives is undecidable, recent results show that when restricted to finite-memory policies the problem is EXPTIME-complete. While the problem is intractable in theory, we present a practical approach to solve the qualitative analysis problem. We designed several heuristics to deal with the exponential complexity, and have used our implementation on a number of well-known POMDP examples for robotics applications. Our results provide the first practical approach to solve the qualitative analysis of robot motion planning with LTL properties in the presence of uncertainty.
AU - Chatterjee, Krishnendu
AU - Chmelik, Martin
AU - Gupta, Raghav
AU - Kanodia, Ayush
ID - 1732
TI - Qualitative analysis of POMDPs with temporal logic specifications for robotics applications
ER -
TY - JOUR
AB - Facial appearance capture is now firmly established within academic research and used extensively across various application domains, perhaps most prominently in the entertainment industry through the design of virtual characters in video games and films. While significant progress has occurred over the last two decades, no single survey currently exists that discusses the similarities, differences, and practical considerations of the available appearance capture techniques as applied to human faces. A central difficulty of facial appearance capture is the way light interacts with skin-which has a complex multi-layered structure-and the interactions that occur below the skin surface can, by definition, only be observed indirectly. In this report, we distinguish between two broad strategies for dealing with this complexity. "Image-based methods" try to exhaustively capture the exact face appearance under different lighting and viewing conditions, and then render the face through weighted image combinations. "Parametric methods" instead fit the captured reflectance data to some parametric appearance model used during rendering, allowing for a more lightweight and flexible representation but at the cost of potentially increased rendering complexity or inexact reproduction. The goal of this report is to provide an overview that can guide practitioners and researchers in assessing the tradeoffs between current approaches and identifying directions for future advances in facial appearance capture.
AU - Klehm, Oliver
AU - Rousselle, Fabrice
AU - Papas, Marios
AU - Bradley, Derek
AU - Hery, Christophe
AU - Bickel, Bernd
AU - Jarosz, Wojciech
AU - Beeler, Thabo
ID - 1734
IS - 2
JF - Computer Graphics Forum
TI - Recent advances in facial appearance capture
VL - 34
ER -
TY - JOUR
AB - This work presents a method for efficiently simplifying the pressure projection step in a liquid simulation. We first devise a straightforward dimension reduction technique that dramatically reduces the cost of solving the pressure projection. Next, we introduce a novel change of basis that satisfies free-surface boundary conditions exactly, regardless of the accuracy of the pressure solve. When combined, these ideas greatly reduce the computational complexity of the pressure solve without compromising free surface boundary conditions at the highest level of detail. Our techniques are easy to parallelize, and they effectively eliminate the computational bottleneck for large liquid simulations.
AU - Ando, Ryoichi
AU - Thürey, Nils
AU - Wojtan, Christopher J
ID - 1735
IS - 2
JF - Computer Graphics Forum
TI - A dimension-reduced pressure solver for liquid simulations
VL - 34
ER -
TY - JOUR
AB - We fabricate and characterize a microscale silicon opto-electromechanical system whose mechanical motion is coupled capacitively to an electrical circuit and optically via radiation pressure to a photonic crystal cavity. To achieve large electromechanical interaction strength, we implement an inverse shadow mask fabrication scheme which obtains capacitor gaps as small as 30 nm while maintaining a silicon surface quality necessary for minimizing optical loss. Using the sensitive optical read-out of the photonic crystal cavity, we characterize the linear and nonlinear capacitive coupling to the fundamental ωm=2π = 63 MHz in-plane flexural motion of the structure, showing that the large electromechanical coupling in such devices may be suitable for realizing efficient microwave-to-optical signal conversion.
AU - Pitanti, Alessandro
AU - Johannes Fink
AU - Safavi-Naeini, Amir H
AU - Hill, Jeff T
AU - Lei, Chan U
AU - Tredicucci, Alessandro
AU - Painter, Oskar J
ID - 1788
IS - 3
JF - Optics Express
TI - Strong opto-electro-mechanical coupling in a silicon photonic crystal cavity
VL - 23
ER -
TY - JOUR
AB - Intellectual disability (ID) has an estimated prevalence of 2-3%. Due to its extreme heterogeneity, the genetic basis of ID remains elusive in many cases. Recently, whole exome sequencing (WES) studies revealed that a large proportion of sporadic cases are caused by de novo gene variants. To identify further genes involved in ID, we performed WES in 250 patients with unexplained ID and their unaffected parents and included exomes of 51 previously sequenced child-parents trios in the analysis. Exome analysis revealed de novo intragenic variants in SET domain-containing 5 (SETD5) in two patients. One patient carried a nonsense variant, and the other an 81 bp deletion located across a splice-donor site. Chromosomal microarray diagnostics further identified four de novo non-recurrent microdeletions encompassing SETD5. CRISPR/Cas9 mutation modelling of the two intragenic variants demonstrated nonsense-mediated decay of the resulting transcripts, pointing to a loss-of-function (LoF) and haploinsufficiency as the common disease-causing mechanism of intragenic SETD5 sequence variants and SETD5-containing microdeletions. In silico domain prediction of SETD5, a predicted SET domain-containing histone methyltransferase (HMT), substantiated the presence of a SET domain and identified a novel putative PHD domain, strengthening a functional link to well-known histone-modifying ID genes. All six patients presented with ID and certain facial dysmorphisms, suggesting that SETD5 sequence variants contribute substantially to the microdeletion 3p25.3 phenotype. The present report of two SETD5 LoF variants in 301 patients demonstrates a prevalence of 0.7% and thus SETD5 variants as a relatively frequent cause of ID.
AU - Kuechler, Alma
AU - Zink, Alexander
AU - Wieland, Thomas
AU - Lüdecke, Hermann
AU - Cremer, Kirsten
AU - Salviati, Leonardo
AU - Magini, Pamela
AU - Najafi, Kimia
AU - Zweier, Christiane
AU - Czeschik, Johanna
AU - Aretz, Stefan
AU - Endele, Sabine
AU - Tamburrino, Federica
AU - Pinato, Claudia
AU - Clementi, Maurizio
AU - Gundlach, Jasmin
AU - Maylahn, Carina
AU - Mazzanti, Laura
AU - Wohlleber, Eva
AU - Schwarzmayr, Thomas
AU - Kariminejad, Roxana
AU - Schlessinger, Avner
AU - Wieczorek, Dagmar
AU - Strom, Tim
AU - Novarino, Gaia
AU - Engels, Hartmut
ID - 1789
IS - 6
JF - European Journal of Human Genetics
TI - Loss-of-function variants of SETD5 cause intellectual disability and the core phenotype of microdeletion 3p25.3 syndrome
VL - 23
ER -
TY - JOUR
AB - Motivated by recent ideas of Harman (Unif. Distrib. Theory, 2010) we develop a new concept of variation of multivariate functions on a compact Hausdorff space with respect to a collection D of subsets. We prove a general version of the Koksma-Hlawka theorem that holds for this notion of variation and discrepancy with respect to D. As special cases, we obtain Koksma-Hlawka inequalities for classical notions, such as extreme or isotropic discrepancy. For extreme discrepancy, our result coincides with the usual Koksma-Hlawka theorem. We show that the space of functions of bounded D-variation contains important discontinuous functions and is closed under natural algebraic operations. Finally, we illustrate the results on concrete integration problems from integral geometry and stereology.
AU - Pausinger, Florian
AU - Svane, Anne
ID - 1792
IS - 6
JF - Journal of Complexity
TI - A Koksma-Hlawka inequality for general discrepancy systems
VL - 31
ER -
TY - JOUR
AB - We present a software platform for reconstructing and analyzing the growth of a plant root system from a time-series of 3D voxelized shapes. It aligns the shapes with each other, constructs a geometric graph representation together with the function that records the time of growth, and organizes the branches into a hierarchy that reflects the order of creation. The software includes the automatic computation of structural and dynamic traits for each root in the system enabling the quantification of growth on fine-scale. These are important advances in plant phenotyping with applications to the study of genetic and environmental influences on growth.
AU - Symonova, Olga
AU - Topp, Christopher
AU - Edelsbrunner, Herbert
ID - 1793
IS - 6
JF - PLoS One
TI - DynamicRoots: A software platform for the reconstruction and analysis of growing plant roots
VL - 10
ER -
TY - JOUR
AB - Noncoding variants in the human MIR137 gene locus increase schizophrenia risk with genome-wide significance. However, the functional consequence of these risk alleles is unknown. Here we examined induced human neurons harboring the minor alleles of four disease-associated single nucleotide polymorphisms in MIR137. We observed increased MIR137 levels compared to those in major allele–carrying cells. microRNA-137 gain of function caused downregulation of the presynaptic target genes complexin-1 (Cplx1), Nsf and synaptotagmin-1 (Syt1), leading to impaired vesicle release. In vivo, miR-137 gain of function resulted in changes in synaptic vesicle pool distribution, impaired induction of mossy fiber long-term potentiation and deficits in hippocampus-dependent learning and memory. By sequestering endogenous miR-137, we were able to ameliorate the synaptic phenotypes. Moreover, reinstatement of Syt1 expression partially restored synaptic plasticity, demonstrating the importance of Syt1 as a miR-137 target. Our data provide new insight into the mechanism by which miR-137 dysregulation can impair synaptic plasticity in the hippocampus.
AU - Sandra Siegert
AU - Seo, Jinsoo
AU - Kwon, Ester J
AU - Rudenko, Andrii
AU - Cho, Sukhee
AU - Wang, Wenyuan
AU - Flood, Zachary C
AU - Martorell, Anthony J
AU - Ericsson, Maria
AU - Mungenast, Alison E
AU - Tsai, Lihuei
ID - 1802
JF - Nature Neuroscience
TI - The schizophrenia risk gene product miR-137 alters presynaptic plasticity
VL - 18
ER -
TY - JOUR
AB - Repeated stress has been suggested to underlie learning and memory deficits via the basolateral amygdala (BLA) and the hippocampus; however, the functional contribution of BLA inputs to the hippocampus and their molecular repercussions are not well understood. Here we show that repeated stress is accompanied by generation of the Cdk5 (cyclin-dependent kinase 5)-activator p25, up-regulation and phosphorylation of glucocorticoid receptors, increased HDAC2 expression, and reduced expression of memoryrelated genes in the hippocampus. A combination of optogenetic and pharmacosynthetic approaches shows that BLA activation is both necessary and sufficient for stress-associated molecular changes and memory impairments. Furthermore, we show that this effect relies on direct glutamatergic projections from the BLA to the dorsal hippocampus. Finally, we show that p25 generation is necessary for the stress-induced memory dysfunction. Taken together, our data provide a neural circuit model for stress-induced hippocampal memory deficits through BLA activity-dependent p25 generation.
AU - Rei, Damien
AU - Mason, Xenos
AU - Seo, Jinsoo
AU - Gräff, Johannes
AU - Rudenko, Andrii
AU - Wang, Jùn
AU - Rueda, Richard
AU - Sandra Siegert
AU - Cho, Sukhee
AU - Canter, Rebecca G
AU - Mungenast, Alison E
AU - Deisseroth, Karl A
AU - Tsai, Lihuei
ID - 1803
IS - 23
JF - PNAS
TI - Basolateral amygdala bidirectionally modulates stress induced hippocampal learning and memory deficits through a p25/Cdk5-dependent pathway
VL - 112
ER -
TY - JOUR
AB - It is known that in classical fluids turbulence typically occurs at high Reynolds numbers. But can turbulence occur at low Reynolds numbers? Here we investigate the transition to turbulence in the classic Taylor-Couette system in which the rotating fluids are manufactured ferrofluids with magnetized nanoparticles embedded in liquid carriers. We find that, in the presence of a magnetic field transverse to the symmetry axis of the system, turbulence can occur at Reynolds numbers that are at least one order of magnitude smaller than those in conventional fluids. This is established by extensive computational ferrohydrodynamics through a detailed investigation of transitions in the flow structure, and characterization of behaviors of physical quantities such as the energy, the wave number, and the angular momentum through the bifurcations. A finding is that, as the magnetic field is increased, onset of turbulence can be determined accurately and reliably. Our results imply that experimental investigation of turbulence may be feasible by using ferrofluids. Our study of transition to and evolution of turbulence in the Taylor-Couette ferrofluidic flow system provides insights into the challenging problem of turbulence control.
AU - Altmeyer, Sebastian
AU - Do, Younghae
AU - Lai, Ying
ID - 1804
JF - Scientific Reports
TI - Transition to turbulence in Taylor-Couette ferrofluidic flow
VL - 5
ER -
TY - JOUR
AB - We consider the problem of deciding whether the persistent homology group of a simplicial pair (K,L) can be realized as the homology H∗(X) of some complex X with L ⊂ X ⊂ K. We show that this problem is NP-complete even if K is embedded in double-struck R3. As a consequence, we show that it is NP-hard to simplify level and sublevel sets of scalar functions on double-struck S3 within a given tolerance constraint. This problem has relevance to the visualization of medical images by isosurfaces. We also show an implication to the theory of well groups of scalar functions: not every well group can be realized by some level set, and deciding whether a well group can be realized is NP-hard.
AU - Attali, Dominique
AU - Bauer, Ulrich
AU - Devillers, Olivier
AU - Glisse, Marc
AU - Lieutier, André
ID - 1805
IS - 8
JF - Computational Geometry: Theory and Applications
TI - Homological reconstruction and simplification in R3
VL - 48
ER -
TY - JOUR
AB - We study a double Cahn-Hilliard type functional related to the Gross-Pitaevskii energy of two-components Bose-Einstein condensates. In the case of large but same order intercomponent and intracomponent coupling strengths, we prove Γ-convergence to a perimeter minimisation functional with an inhomogeneous surface tension. We study the asymptotic behavior of the surface tension as the ratio between the intercomponent and intracomponent coupling strengths becomes very small or very large and obtain good agreement with the physical literature. We obtain as a consequence, symmetry breaking of the minimisers for the harmonic potential.
AU - Goldman, Michael
AU - Royo-Letelier, Jimena
ID - 1807
IS - 3
JF - ESAIM - Control, Optimisation and Calculus of Variations
TI - Sharp interface limit for two components Bose-Einstein condensates
VL - 21
ER -
TY - JOUR
AU - Gupta, Ashutosh
AU - Henzinger, Thomas A
ID - 1808
IS - 2
JF - ACM Transactions on Modeling and Computer Simulation
TI - Guest editors' introduction to special issue on computational methods in systems biology
VL - 25
ER -
TY - JOUR
AB - Background: Indirect genetic effects (IGEs) occur when genes expressed in one individual alter the expression of traits in social partners. Previous studies focused on the evolutionary consequences and evolutionary dynamics of IGEs, using equilibrium solutions to predict phenotypes in subsequent generations. However, whether or not such steady states may be reached may depend on the dynamics of interactions themselves. Results: In our study, we focus on the dynamics of social interactions and indirect genetic effects and investigate how they modify phenotypes over time. Unlike previous IGE studies, we do not analyse evolutionary dynamics; rather we consider within-individual phenotypic changes, also referred to as phenotypic plasticity. We analyse iterative interactions, when individuals interact in a series of discontinuous events, and investigate the stability of steady state solutions and the dependence on model parameters, such as population size, strength, and the nature of interactions. We show that for interactions where a feedback loop occurs, the possible parameter space of interaction strength is fairly limited, affecting the evolutionary consequences of IGEs. We discuss the implications of our results for current IGE model predictions and their limitations.
AU - Trubenova, Barbora
AU - Novak, Sebastian
AU - Hager, Reinmar
ID - 1809
IS - 5
JF - PLoS One
TI - Indirect genetic effects and the dynamics of social interactions
VL - 10
ER -
TY - JOUR
AB - Combining antibiotics is a promising strategy for increasing treatment efficacy and for controlling resistance evolution. When drugs are combined, their effects on cells may be amplified or weakened, that is the drugs may show synergistic or antagonistic interactions. Recent work revealed the underlying mechanisms of such drug interactions by elucidating the drugs'; joint effects on cell physiology. Moreover, new treatment strategies that use drug combinations to exploit evolutionary tradeoffs were shown to affect the rate of resistance evolution in predictable ways. High throughput studies have further identified drug candidates based on their interactions with established antibiotics and general principles that enable the prediction of drug interactions were suggested. Overall, the conceptual and technical foundation for the rational design of potent drug combinations is rapidly developing.
AU - Bollenbach, Mark Tobias
ID - 1810
JF - Current Opinion in Microbiology
TI - Antimicrobial interactions: Mechanisms and implications for drug discovery and resistance evolution
VL - 27
ER -
TY - JOUR
AB - Atomic form factors are widely used for the characterization of targets and specimens, from crystallography to biology. By using recent mathematical results, here we derive an analytical expression for the atomic form factor within the independent particle model constructed from nonrelativistic screened hydrogenic wave functions. The range of validity of this analytical expression is checked by comparing the analytically obtained form factors with the ones obtained within the Hartee-Fock method. As an example, we apply our analytical expression for the atomic form factor to evaluate the differential cross section for Rayleigh scattering off neutral atoms.
AU - Safari, Laleh
AU - Santos, José
AU - Amaro, Pedro
AU - Jänkälä, Kari
AU - Fratini, Filippo
ID - 1811
IS - 5
JF - Journal of Mathematical Physics
TI - Analytical evaluation of atomic form factors: Application to Rayleigh scattering
VL - 56
ER -
TY - JOUR
AB - We investigate the occurrence of rotons in a quadrupolar Bose–Einstein condensate confined to two dimensions. Depending on the particle density, the ratio of the contact and quadrupole–quadrupole interactions, and the alignment of the quadrupole moments with respect to the confinement plane, the dispersion relation features two or four point-like roton minima or one ring-shaped minimum. We map out the entire parameter space of the roton behavior and identify the instability regions. We propose to observe the exotic rotons by monitoring the characteristic density wave dynamics resulting from a short local perturbation, and discuss the possibilities to detect the predicted effects in state-of-the-art experiments with ultracold homonuclear molecules.
AU - Lahrz, Martin
AU - Lemeshko, Mikhail
AU - Mathey, Ludwig
ID - 1812
IS - 4
JF - New Journal of Physics
TI - Exotic roton excitations in quadrupolar Bose–Einstein condensates
VL - 17
ER -
TY - JOUR
AB - We develop a microscopic theory describing a quantum impurity whose rotational degree of freedom is coupled to a many-particle bath. We approach the problem by introducing the concept of an “angulon”—a quantum rotor dressed by a quantum field—and reveal its quasiparticle properties using a combination of variational and diagrammatic techniques. Our theory predicts renormalization of the impurity rotational structure, such as that observed in experiments with molecules in superfluid helium droplets, in terms of a rotational Lamb shift induced by the many-particle environment. Furthermore, we discover a rich many-body-induced fine structure, emerging in rotational spectra due to a redistribution of angular momentum within the quantum many-body system.
AU - Schmidt, Richard
AU - Lemeshko, Mikhail
ID - 1813
IS - 20
JF - Physical Review Letters
TI - Rotation of quantum impurities in the presence of a many-body environment
VL - 114
ER -
TY - JOUR
AB - We present an efficient wavefront tracking algorithm for animating bodies of water that interact with their environment. Our contributions include: a novel wavefront tracking technique that enables dispersion, refraction, reflection, and diffraction in the same simulation; a unique multivalued function interpolation method that enables our simulations to elegantly sidestep the Nyquist limit; a dispersion approximation for efficiently amplifying the number of simulated waves by several orders of magnitude; and additional extensions that allow for time-dependent effects and interactive artistic editing of the resulting animation. Our contributions combine to give us multitudes more wave details than similar algorithms, while maintaining high frame rates and allowing close camera zooms.
AU - Jeschke, Stefan
AU - Wojtan, Christopher J
ID - 1814
IS - 3
JF - ACM Transactions on Graphics
TI - Water wave animation via wavefront parameter interpolation
VL - 34
ER -
TY - JOUR
AB - Vertebrates have a unique 3D body shape in which correct tissue and organ shape and alignment are essential for function. For example, vision requires the lens to be centred in the eye cup which must in turn be correctly positioned in the head. Tissue morphogenesis depends on force generation, force transmission through the tissue, and response of tissues and extracellular matrix to force. Although a century ago D'Arcy Thompson postulated that terrestrial animal body shapes are conditioned by gravity, there has been no animal model directly demonstrating how the aforementioned mechano-morphogenetic processes are coordinated to generate a body shape that withstands gravity. Here we report a unique medaka fish (Oryzias latipes) mutant, hirame (hir), which is sensitive to deformation by gravity. hir embryos display a markedly flattened body caused by mutation of YAP, a nuclear executor of Hippo signalling that regulates organ size. We show that actomyosin-mediated tissue tension is reduced in hir embryos, leading to tissue flattening and tissue misalignment, both of which contribute to body flattening. By analysing YAP function in 3D spheroids of human cells, we identify the Rho GTPase activating protein ARHGAP18 as an effector of YAP in controlling tissue tension. Together, these findings reveal a previously unrecognised function of YAP in regulating tissue shape and alignment required for proper 3D body shape. Understanding this morphogenetic function of YAP could facilitate the use of embryonic stem cells to generate complex organs requiring correct alignment of multiple tissues.
AU - Porazinski, Sean
AU - Wang, Huijia
AU - Asaoka, Yoichi
AU - Behrndt, Martin
AU - Miyamoto, Tatsuo
AU - Morita, Hitoshi
AU - Hata, Shoji
AU - Sasaki, Takashi
AU - Krens, Gabriel
AU - Osada, Yumi
AU - Asaka, Satoshi
AU - Momoi, Akihiro
AU - Linton, Sarah
AU - Miesfeld, Joel
AU - Link, Brian
AU - Senga, Takeshi
AU - Castillo Morales, Atahualpa
AU - Urrutia, Araxi
AU - Shimizu, Nobuyoshi
AU - Nagase, Hideaki
AU - Matsuura, Shinya
AU - Bagby, Stefan
AU - Kondoh, Hisato
AU - Nishina, Hiroshi
AU - Heisenberg, Carl-Philipp J
AU - Furutani Seiki, Makoto
ID - 1817
IS - 7551
JF - Nature
TI - YAP is essential for tissue tension to ensure vertebrate 3D body shape
VL - 521
ER -
TY - JOUR
AB - Why do species not adapt to ever-wider ranges of conditions, gradually expanding their ecological niche and geographic range? Gene flow across environments has two conflicting effects: although it increases genetic variation, which is a prerequisite for adaptation, gene flow may swamp adaptation to local conditions. In 1956, Haldane proposed that, when the environment varies across space, "swamping" by gene flow creates a positive feedback between low population size and maladaptation, leading to a sharp range margin. However, current deterministic theory shows that, when variance can evolve, there is no such limit. Using simple analytical tools and simulations, we show that genetic drift can generate a sharp margin to a species' range, by reducing genetic variance below the level needed for adaptation to spatially variable conditions. Aided by separation of ecological and evolutionary timescales, the identified effective dimensionless parameters reveal a simple threshold that predicts when adaptation at the range margin fails. Two observable parameters determine the threshold: (i) the effective environmental gradient, which can be measured by the loss of fitness due to dispersal to a different environment; and (ii) the efficacy of selection relative to genetic drift. The theory predicts sharp range margins even in the absence of abrupt changes in the environment. Furthermore, it implies that gradual worsening of conditions across a species' habitat may lead to a sudden range fragmentation, when adaptation to a wide span of conditions within a single species becomes impossible.
AU - Polechova, Jitka
AU - Barton, Nicholas H
ID - 1818
IS - 20
JF - PNAS
TI - Limits to adaptation along environmental gradients
VL - 112
ER -
TY - JOUR
AB - The sessile life style of plants creates the need to deal with an often adverse environment, in which water availability can change on a daily basis, challenging the cellular physiology and integrity. Changes in osmotic conditions disrupt the equilibrium of the plasma membrane: hypoosmotic conditions increase and hyperosmotic environment decrease the cell volume. Here, we show that short-term extracellular osmotic treatments are closely followed by a shift in the balance between endocytosis and exocytosis in root meristem cells. Acute hyperosmotic treatments (ionic and nonionic) enhance clathrin-mediated endocytosis simultaneously attenuating exocytosis, whereas hypoosmotic treatments have the opposite effects. In addition to clathrin recruitment to the plasma membrane, components of early endocytic trafficking are essential during hyperosmotic stress responses. Consequently, growth of seedlings defective in elements of clathrin or early endocytic machinery is more sensitive to hyperosmotic treatments. We also found that the endocytotic response to a change of osmotic status in the environment is dominant over the presumably evolutionary more recent regulatory effect of plant hormones, such as auxin. These results imply that osmotic perturbation influences the balance between endocytosis and exocytosis acting through clathrin-mediated endocytosis. We propose that tension on the plasma membrane determines the addition or removal of membranes at the cell surface, thus preserving cell integrity.
AU - Zwiewka, Marta
AU - Nodzyński, Tomasz
AU - Robert, Stéphanie
AU - Vanneste, Steffen
AU - Friml, Jiřĺ
ID - 1819
IS - 8
JF - Molecular Plant
TI - Osmotic stress modulates the balance between exocytosis and clathrin mediated endocytosis in Arabidopsis thaliana
VL - 8
ER -
TY - CONF
AB - We consider partially observable Markov decision processes (POMDPs) with a set of target states and every transition is associated with an integer cost. The optimization objec- tive we study asks to minimize the expected total cost till the target set is reached, 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 and the bound is double exponential; (ii) we show that the problem of approximating the optimal cost is decidable and present ap- proximation 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 present efficient stopping criteria for the algorithm and show experimentally that it performs well in many examples.
AU - Chatterjee, Krishnendu
AU - Chmelik, Martin
AU - Gupta, Raghav
AU - Kanodia, Ayush
ID - 1820
T2 - Proceedings of the Twenty-Ninth AAAI Conference on Artificial Intelligence
TI - Optimal cost almost-sure reachability in POMDPs
VL - 5
ER -
TY - JOUR
AB - Abstract Drug combinations are increasingly important in disease treatments, for combating drug resistance, and for elucidating fundamental relationships in cell physiology. When drugs are combined, their individual effects on cells may be amplified or weakened. Such drug interactions are crucial for treatment efficacy, but their underlying mechanisms remain largely unknown. To uncover the causes of drug interactions, we developed a systematic approach based on precise quantification of the individual and joint effects of antibiotics on growth of genome-wide Escherichia coli gene deletion strains. We found that drug interactions between antibiotics representing the main modes of action are highly robust to genetic perturbation. This robustness is encapsulated in a general principle of bacterial growth, which enables the quantitative prediction of mutant growth rates under drug combinations. Rare violations of this principle exposed recurring cellular functions controlling drug interactions. In particular, we found that polysaccharide and ATP synthesis control multiple drug interactions with previously unexplained mechanisms, and small molecule adjuvants targeting these functions synthetically reshape drug interactions in predictable ways. These results provide a new conceptual framework for the design of multidrug combinations and suggest that there are universal mechanisms at the heart of most drug interactions. Synopsis A general principle of bacterial growth enables the prediction of mutant growth rates under drug combinations. Rare violations of this principle expose cellular functions that control drug interactions and can be targeted by small molecules to alter drug interactions in predictable ways. Drug interactions between antibiotics are highly robust to genetic perturbations. A general principle of bacterial growth enables the prediction of mutant growth rates under drug combinations. Rare violations of this principle expose cellular functions that control drug interactions. Diverse drug interactions are controlled by recurring cellular functions, including LPS synthesis and ATP synthesis. A general principle of bacterial growth enables the prediction of mutant growth rates under drug combinations. Rare violations of this principle expose cellular functions that control drug interactions and can be targeted by small molecules to alter drug interactions in predictable ways.
AU - Chevereau, Guillaume
AU - Bollenbach, Mark Tobias
ID - 1823
IS - 4
JF - Molecular Systems Biology
TI - Systematic discovery of drug interaction mechanisms
VL - 11
ER -
TY - JOUR
AB - Condensation phenomena arise through a collective behaviour of particles. They are observed in both classical and quantum systems, ranging from the formation of traffic jams in mass transport models to the macroscopic occupation of the energetic ground state in ultra-cold bosonic gases (Bose-Einstein condensation). Recently, it has been shown that a driven and dissipative system of bosons may form multiple condensates. Which states become the condensates has, however, remained elusive thus far. The dynamics of this condensation are described by coupled birth-death processes, which also occur in evolutionary game theory. Here we apply concepts from evolutionary game theory to explain the formation of multiple condensates in such driven-dissipative bosonic systems. We show that the vanishing of relative entropy production determines their selection. The condensation proceeds exponentially fast, but the system never comes to rest. Instead, the occupation numbers of condensates may oscillate, as we demonstrate for a rock-paper-scissors game of condensates.
AU - Knebel, Johannes
AU - Weber, Markus
AU - Krüger, Torben H
AU - Frey, Erwin
ID - 1824
JF - Nature Communications
TI - Evolutionary games of condensates in coupled birth-death processes
VL - 6
ER -
TY - JOUR
AB - Bow-tie or hourglass structure is a common architectural feature found in many biological systems. A bow-tie in a multi-layered structure occurs when intermediate layers have much fewer components than the input and output layers. Examples include metabolism where a handful of building blocks mediate between multiple input nutrients and multiple output biomass components, and signaling networks where information from numerous receptor types passes through a small set of signaling pathways to regulate multiple output genes. Little is known, however, about how bow-tie architectures evolve. Here, we address the evolution of bow-tie architectures using simulations of multi-layered systems evolving to fulfill a given input-output goal. We find that bow-ties spontaneously evolve when the information in the evolutionary goal can be compressed. Mathematically speaking, bow-ties evolve when the rank of the input-output matrix describing the evolutionary goal is deficient. The maximal compression possible (the rank of the goal) determines the size of the narrowest part of the network—that is the bow-tie. A further requirement is that a process is active to reduce the number of links in the network, such as product-rule mutations, otherwise a non-bow-tie solution is found in the evolutionary simulations. This offers a mechanism to understand a common architectural principle of biological systems, and a way to quantitate the effective rank of the goals under which they evolved.
AU - Friedlander, Tamar
AU - Mayo, Avraham
AU - Tlusty, Tsvi
AU - Alon, Uri
ID - 1827
IS - 3
JF - PLoS Computational Biology
TI - Evolution of bow-tie architectures in biology
VL - 11
ER -
TY - JOUR
AB - We construct a non-linear Markov process connected with a biological model of a bacterial genome recombination. The description of invariant measures of this process gives us the solution of one problem in elementary probability theory.
AU - Akopyan, Arseniy
AU - Pirogov, Sergey
AU - Rybko, Aleksandr
ID - 1828
IS - 1
JF - Journal of Statistical Physics
TI - Invariant measures of genetic recombination process
VL - 160
ER -
TY - JOUR
AB - To prevent epidemics, insect societies have evolved collective disease defences that are highly effective at curing exposed individuals and limiting disease transmission to healthy group members. Grooming is an important sanitary behaviour—either performed towards oneself (self-grooming) or towards others (allogrooming)—to remove infectious agents from the body surface of exposed individuals, but at the risk of disease contraction by the groomer. We use garden ants (Lasius neglectus) and the fungal pathogen Metarhizium as a model system to study how pathogen presence affects self-grooming and allogrooming between exposed and healthy individuals. We develop an epidemiological SIS model to explore how experimentally observed grooming patterns affect disease spread within the colony, thereby providing a direct link between the expression and direction of sanitary behaviours, and their effects on colony-level epidemiology. We find that fungus-exposed ants increase self-grooming, while simultaneously decreasing allogrooming. This behavioural modulation seems universally adaptive and is predicted to contain disease spread in a great variety of host–pathogen systems. In contrast, allogrooming directed towards pathogen-exposed individuals might both increase and decrease disease risk. Our model reveals that the effect of allogrooming depends on the balance between pathogen infectiousness and efficiency of social host defences, which are likely to vary across host–pathogen systems.
AU - Theis, Fabian
AU - Ugelvig, Line V
AU - Marr, Carsten
AU - Cremer, Sylvia
ID - 1830
IS - 1669
JF - Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
TI - Opposing effects of allogrooming on disease transmission in ant societies
VL - 370
ER -
TY - JOUR
AB - This paper introduces a theme issue presenting the latest developments in research on the impacts of sociality on health and fitness. The articles that follow cover research on societies ranging from insects to humans. Variation in measures of fitness (i.e. survival and reproduction) has been linked to various aspects of sociality in humans and animals alike, and variability in individual health and condition has been recognized as a key mediator of these relationships. Viewed from a broad evolutionary perspective, the evolutionary transitions from a solitary lifestyle to group living have resulted in several new health-related costs and benefits of sociality. Social transmission of parasites within groups represents a major cost of group living, but some behavioural mechanisms, such as grooming, have evolved repeatedly to reduce this cost. Group living also has created novel costs in terms of altered susceptibility to infectious and non-infectious disease as a result of the unavoidable physiological consequences of social competition and integration, which are partly alleviated by social buffering in some vertebrates. Here, we define the relevant aspects of sociality, summarize their health-related costs and benefits, and discuss possible fitness measures in different study systems. Given the pervasive effects of social factors on health and fitness, we propose a synthesis of existing conceptual approaches in disease ecology, ecological immunology and behavioural neurosciences by adding sociality as a key factor, with the goal to generate a broader framework for organismal integration of health-related research.
AU - Kappeler, Peter
AU - Cremer, Sylvia
AU - Nunn, Charles
ID - 1831
IS - 1669
JF - Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
TI - Sociality and health: Impacts of sociality on disease susceptibility and transmission in animal and human societies
VL - 370
ER -
TY - JOUR
AB - Linearizability of concurrent data structures is usually proved by monolithic simulation arguments relying on the identification of the so-called linearization points. Regrettably, such proofs, whether manual or automatic, are often complicated and scale poorly to advanced non-blocking concurrency patterns, such as helping and optimistic updates. In response, we propose a more modular way of checking linearizability of concurrent queue algorithms that does not involve identifying linearization points. We reduce the task of proving linearizability with respect to the queue specification to establishing four basic properties, each of which can be proved independently by simpler arguments. As a demonstration of our approach, we verify the Herlihy and Wing queue, an algorithm that is challenging to verify by a simulation proof.
AU - Chakraborty, Soham
AU - Henzinger, Thomas A
AU - Sezgin, Ali
AU - Vafeiadis, Viktor
ID - 1832
IS - 1
JF - Logical Methods in Computer Science
TI - Aspect-oriented linearizability proofs
VL - 11
ER -
TY - JOUR
AB - Huge body of evidences demonstrated that volatile anesthetics affect the hippocampal neurogenesis and neurocognitive functions, and most of them showed impairment at anesthetic dose. Here, we investigated the effect of low dose (1.8%) sevoflurane on hippocampal neurogenesis and dentate gyrus-dependent learning. Neonatal rats at postnatal day 4 to 6 (P4-6) were treated with 1.8% sevoflurane for 6 hours. Neurogenesis was quantified by bromodeoxyuridine labeling and electrophysiology recording. Four and seven weeks after treatment, the Morris water maze and contextual-fear discrimination learning tests were performed to determine the influence on spatial learning and pattern separation. A 6-hour treatment with 1.8% sevoflurane promoted hippocampal neurogenesis and increased the survival of newborn cells and the proportion of immature granular cells in the dentate gyrus of neonatal rats. Sevoflurane-treated rats performed better during the training days of the Morris water maze test and in contextual-fear discrimination learning test. These results suggest that a subanesthetic dose of sevoflurane promotes hippocampal neurogenesis in neonatal rats and facilitates their performance in dentate gyrus-dependent learning tasks.
AU - Chen, Chong
AU - Wang, Chao
AU - Zhao, Xuan
AU - Zhou, Tao
AU - Xu, Dao
AU - Wang, Zhi
AU - Wang, Ying
ID - 1834
IS - 2
JF - ASN Neuro
TI - Low-dose sevoflurane promoteshippocampal neurogenesis and facilitates the development of dentate gyrus-dependent learning in neonatal rats
VL - 7
ER -
TY - CONF
AB - The behaviour of gene regulatory networks (GRNs) is typically analysed using simulation-based statistical testing-like methods. In this paper, we demonstrate that we can replace this approach by a formal verification-like method that gives higher assurance and scalability. We focus on Wagner’s weighted GRN model with varying weights, which is used in evolutionary biology. In the model, weight parameters represent the gene interaction strength that may change due to genetic mutations. For a property of interest, we synthesise the constraints over the parameter space that represent the set of GRNs satisfying the property. We experimentally show that our parameter synthesis procedure computes the mutational robustness of GRNs –an important problem of interest in evolutionary biology– more efficiently than the classical simulation method. We specify the property in linear temporal logics. We employ symbolic bounded model checking and SMT solving to compute the space of GRNs that satisfy the property, which amounts to synthesizing a set of linear constraints on the weights.
AU - Giacobbe, Mirco
AU - Guet, Calin C
AU - Gupta, Ashutosh
AU - Henzinger, Thomas A
AU - Paixao, Tiago
AU - Petrov, Tatjana
ID - 1835
TI - Model checking gene regulatory networks
VL - 9035
ER -
TY - CONF
AB - In the standard framework for worst-case execution time (WCET) analysis of programs, the main data structure is a single instance of integer linear programming (ILP) that represents the whole program. The instance of this NP-hard problem must be solved to find an estimate forWCET, and it must be refined if the estimate is not tight.We propose a new framework for WCET analysis, based on abstract segment trees (ASTs) as the main data structure. The ASTs have two advantages. First, they allow computing WCET by solving a number of independent small ILP instances. Second, ASTs store more expressive constraints, thus enabling a more efficient and precise refinement procedure. In order to realize our framework algorithmically, we develop an algorithm for WCET estimation on ASTs, and we develop an interpolation-based counterexample-guided refinement scheme for ASTs. Furthermore, we extend our framework to obtain parametric estimates of WCET. We experimentally evaluate our approach on a set of examples from WCET benchmark suites and linear-algebra packages. We show that our analysis, with comparable effort, provides WCET estimates that in many cases significantly improve those computed by existing tools.
AU - Cerny, Pavol
AU - Henzinger, Thomas A
AU - Kovács, Laura
AU - Radhakrishna, Arjun
AU - Zwirchmayr, Jakob
ID - 1836
TI - Segment abstraction for worst-case execution time analysis
VL - 9032
ER -
TY - JOUR
AB - Transition to turbulence in straight pipes occurs in spite of the linear stability of the laminar Hagen-Poiseuille flow if both the amplitude of flow perturbations and the Reynolds number Re exceed a minimum threshold (subcritical transition). As the pipe curvature increases, centrifugal effects become important, modifying the basic flow as well as the most unstable linear modes. If the curvature (tube-to-coiling diameter d/D) is sufficiently large, a Hopf bifurcation (supercritical instability) is encountered before turbulence can be excited (subcritical instability). We trace the instability thresholds in the Re - d/D parameter space in the range 0.01 ≤ d/D\ ≤ 0.1 by means of laser-Doppler velocimetry and determine the point where the subcritical and supercritical instabilities meet. Two different experimental set-ups are used: a closed system where the pipe forms an axisymmetric torus and an open system employing a helical pipe. Implications for the measurement of friction factors in curved pipes are discussed.
AU - Kühnen, Jakob
AU - Braunshier, P
AU - Schwegel, M
AU - Kuhlmann, Hendrik
AU - Hof, Björn
ID - 1837
IS - 5
JF - Journal of Fluid Mechanics
TI - Subcritical versus supercritical transition to turbulence in curved pipes
VL - 770
ER -
TY - CONF
AB - Synthesis of program parts is particularly useful for concurrent systems. However, most approaches do not support common design tasks, like modifying a single process without having to re-synthesize or verify the whole system. Assume-guarantee synthesis (AGS) provides robustness against modifications of system parts, but thus far has been limited to the perfect information setting. This means that local variables cannot be hidden from other processes, which renders synthesis results cumbersome or even impossible to realize.We resolve this shortcoming by defining AGS under partial information. We analyze the complexity and decidability in different settings, showing that the problem has a high worstcase complexity and is undecidable in many interesting cases. Based on these observations, we present a pragmatic algorithm based on bounded synthesis, and demonstrate its practical applicability on several examples.
AU - Bloem, Roderick
AU - Chatterjee, Krishnendu
AU - Jacobs, Swen
AU - Könighofer, Robert
ID - 1838
TI - Assume-guarantee synthesis for concurrent reactive programs with partial information
VL - 9035
ER -
TY - CONF
AB - We present MultiGain, a tool to synthesize strategies for Markov decision processes (MDPs) with multiple mean-payoff objectives. Our models are described in PRISM, and our tool uses the existing interface and simulator of PRISM. Our tool extends PRISM by adding novel algorithms for multiple mean-payoff objectives, and also provides features such as (i) generating strategies and exploring them for simulation, and checking them with respect to other properties; and (ii) generating an approximate Pareto curve for two mean-payoff objectives. In addition, we present a new practical algorithm for the analysis of MDPs with multiple mean-payoff objectives under memoryless strategies.
AU - Brázdil, Tomáš
AU - Chatterjee, Krishnendu
AU - Forejt, Vojtěch
AU - Kučera, Antonín
ID - 1839
TI - Multigain: A controller synthesis tool for MDPs with multiple mean-payoff objectives
VL - 9035
ER -
TY - JOUR
AB - In this paper, we present a method for reducing a regular, discrete-time Markov chain (DTMC) to another DTMC with a given, typically much smaller number of states. The cost of reduction is defined as the Kullback-Leibler divergence rate between a projection of the original process through a partition function and a DTMC on the correspondingly partitioned state space. Finding the reduced model with minimal cost is computationally expensive, as it requires an exhaustive search among all state space partitions, and an exact evaluation of the reduction cost for each candidate partition. Our approach deals with the latter problem by minimizing an upper bound on the reduction cost instead of minimizing the exact cost. The proposed upper bound is easy to compute and it is tight if the original chain is lumpable with respect to the partition. Then, we express the problem in the form of information bottleneck optimization, and propose using the agglomerative information bottleneck algorithm for searching a suboptimal partition greedily, rather than exhaustively. The theory is illustrated with examples and one application scenario in the context of modeling bio-molecular interactions.
AU - Geiger, Bernhard
AU - Petrov, Tatjana
AU - Kubin, Gernot
AU - Koeppl, Heinz
ID - 1840
IS - 4
JF - IEEE Transactions on Automatic Control
SN - 0018-9286
TI - Optimal Kullback-Leibler aggregation via information bottleneck
VL - 60
ER -
TY - JOUR
AB - We propose a new family of message passing techniques for MAP estimation in graphical models which we call Sequential Reweighted Message Passing (SRMP). Special cases include well-known techniques such as Min-Sum Diffusion (MSD) and a faster Sequential Tree-Reweighted Message Passing (TRW-S). Importantly, our derivation is simpler than the original derivation of TRW-S, and does not involve a decomposition into trees. This allows easy generalizations. The new family of algorithms can be viewed as a generalization of TRW-S from pairwise to higher-order graphical models. We test SRMP on several real-world problems with promising results.
AU - Kolmogorov, Vladimir
ID - 1841
IS - 5
JF - IEEE Transactions on Pattern Analysis and Machine Intelligence
TI - A new look at reweighted message passing
VL - 37
ER -
TY - JOUR
AU - Bod'ová, Katarína
AU - Paydarfar, David
AU - Forger, Daniel
ID - 1843
JF - Journal of Theoretical Biology
TI - Erratum to: Characterizing spiking in noisy type II neurons [J. Theor. Biol. 365 (2015) 40–54]
VL - 373
ER -
TY - JOUR
AB - Based on extrapolation from excitatory synapses, it is often assumed that depletion of the releasable pool of synaptic vesicles is the main factor underlying depression at inhibitory synapses. In this issue of Neuron, using subcellular patch-clamp recording from inhibitory presynaptic terminals, Kawaguchi and Sakaba (2015) show that at Purkinje cell-deep cerebellar nuclei neuron synapses, changes in presynaptic action potential waveform substantially contribute to synaptic depression. Based on extrapolation from excitatory synapses, it is often assumed that depletion of the releasable pool of synaptic vesicles is the main factor underlying depression at inhibitory synapses. In this issue of Neuron, using subcellular patch-clamp recording from inhibitory presynaptic terminals, Kawaguchi and Sakaba (2015) show that at Purkinje cell-deep cerebellar nuclei neuron synapses, changes in presynaptic action potential waveform substantially contribute to synaptic depression.
AU - Vandael, David H
AU - Espinoza Martinez, Claudia M
AU - Jonas, Peter M
ID - 1845
IS - 6
JF - Neuron
TI - Excitement about inhibitory presynaptic terminals
VL - 85
ER -
TY - JOUR
AB - Modal transition systems (MTS) is a well-studied specification formalism of reactive systems supporting a step-wise refinement methodology. Despite its many advantages, the formalism as well as its currently known extensions are incapable of expressing some practically needed aspects in the refinement process like exclusive, conditional and persistent choices. We introduce a new model called parametric modal transition systems (PMTS) together with a general modal refinement notion that overcomes many of the limitations. We investigate the computational complexity of modal and thorough refinement checking on PMTS and its subclasses and provide a direct encoding of the modal refinement problem into quantified Boolean formulae, allowing us to employ state-of-the-art QBF solvers for modal refinement checking. The experiments we report on show that the feasibility of refinement checking is more influenced by the degree of nondeterminism rather than by the syntactic restrictions on the types of formulae allowed in the description of the PMTS.
AU - Beneš, Nikola
AU - Kretinsky, Jan
AU - Larsen, Kim
AU - Möller, Mikael
AU - Sickert, Salomon
AU - Srba, Jiří
ID - 1846
IS - 2-3
JF - Acta Informatica
TI - Refinement checking on parametric modal transition systems
VL - 52
ER -
TY - JOUR
AU - Grones, Peter
AU - Friml, Jiřĺ
ID - 1847
IS - 3
JF - Molecular Plant
TI - ABP1: Finally docking
VL - 8
ER -
TY - JOUR
AB - The ability to escape apoptosis is a hallmark of cancer-initiating cells and a key factor of resistance to oncolytic therapy. Here, we identify FAM96A as a ubiquitous, evolutionarily conserved apoptosome-activating protein and investigate its potential pro-apoptotic tumor suppressor function in gastrointestinal stromal tumors (GISTs). Interaction between FAM96A and apoptotic peptidase activating factor 1 (APAF1) was identified in yeast two-hybrid screen and further studied by deletion mutants, glutathione-S-transferase pull-down, co-immunoprecipitation and immunofluorescence. Effects of FAM96A overexpression and knock-down on apoptosis sensitivity were examined in cancer cells and zebrafish embryos. Expression of FAM96A in GISTs and histogenetically related cells including interstitial cells of Cajal (ICCs), “fibroblast-like cells” (FLCs) and ICC stem cells (ICC-SCs) was investigated by Northern blotting, reverse transcription—polymerase chain reaction, immunohistochemistry and Western immunoblotting. Tumorigenicity of GIST cells and transformed murine ICC-SCs stably transduced to re-express FAM96A was studied by xeno- and allografting into immunocompromised mice. FAM96A was found to bind APAF1 and to enhance the induction of mitochondrial apoptosis. FAM96A protein or mRNA was dramatically reduced or lost in 106 of 108 GIST samples representing three independent patient cohorts. Whereas ICCs, ICC-SCs and FLCs, the presumed normal counterparts of GIST, were found to robustly express FAM96A protein and mRNA, FAM96A expression was much reduced in tumorigenic ICC-SCs. Re-expression of FAM96A in GIST cells and transformed ICC-SCs increased apoptosis sensitivity and diminished tumorigenicity. Our data suggest FAM96A is a novel pro-apoptotic tumor suppressor that is lost during GIST tumorigenesis.
AU - Schwamb, Bettina
AU - Pick, Robert
AU - Fernández, Sara
AU - Völp, Kirsten
AU - Heering, Jan
AU - Dötsch, Volker
AU - Bösser, Susanne
AU - Jung, Jennifer
AU - Beinoravičiute Kellner, Rasa
AU - Wesely, Josephine
AU - Zörnig, Inka
AU - Hammerschmidt, Matthias
AU - Nowak, Matthias
AU - Penzel, Roland
AU - Zatloukal, Kurt
AU - Joos, Stefan
AU - Rieker, Ralf
AU - Agaimy, Abbas
AU - Söder, Stephan
AU - Reid Lombardo, Kmarie
AU - Kendrick, Michael
AU - Bardsley, Michael
AU - Hayashi, Yujiro
AU - Asuzu, David
AU - Syed, Sabriya
AU - Ördög, Tamás
AU - Zörnig, Martin
ID - 1848
IS - 6
JF - International Journal of Cancer
TI - FAM96A is a novel pro-apoptotic tumor suppressor in gastrointestinal stromal tumors
VL - 137
ER -
TY - JOUR
AB - Cell polarity is a fundamental property of pro- and eukaryotic cells. It is necessary for coordination of cell division, cell morphogenesis and signaling processes. How polarity is generated and maintained is a complex issue governed by interconnected feed-back regulations between small GTPase signaling and membrane tension-based signaling that controls membrane trafficking, and cytoskeleton organization and dynamics. Here, we will review the potential role for calcium as a crucial signal that connects and coordinates the respective processes during polarization processes in plants. This article is part of a Special Issue entitled: 13th European Symposium on Calcium.
AU - Himschoot, Ellie
AU - Beeckman, Tom
AU - Friml, Jiřĺ
AU - Vanneste, Steffen
ID - 1849
IS - 9
JF - Biochimica et Biophysica Acta - Molecular Cell Research
TI - Calcium is an organizer of cell polarity in plants
VL - 1853
ER -
TY - JOUR
AB - Entomopathogenic fungi are potent biocontrol agents that are widely used against insect pests, many of which are social insects. Nevertheless, theoretical investigations of their particular life history are scarce. We develop a model that takes into account the main distinguishing features between traditionally studied diseases and obligate killing pathogens, like the (biocontrol-relevant) insect-pathogenic fungi Metarhizium and Beauveria. First, obligate killing entomopathogenic fungi produce new infectious particles (conidiospores) only after host death and not yet on the living host. Second, the killing rates of entomopathogenic fungi depend strongly on the initial exposure dosage, thus we explicitly consider the pathogen load of individual hosts. Further, we make the model applicable not only to solitary host species, but also to group living species by incorporating social interactions between hosts, like the collective disease defences of insect societies. Our results identify the optimal killing rate for the pathogen that minimises its invasion threshold. Furthermore, we find that the rate of contact between hosts has an ambivalent effect: dense interaction networks between individuals are considered to facilitate disease outbreaks because of increased pathogen transmission. In social insects, this is compensated by their collective disease defences, i.e., social immunity. For the type of pathogens considered here, we show that even without social immunity, high contact rates between live individuals dilute the pathogen in the host colony and hence can reduce individual pathogen loads below disease-causing levels.
AU - Novak, Sebastian
AU - Cremer, Sylvia
ID - 1850
IS - 5
JF - Journal of Theoretical Biology
TI - Fungal disease dynamics in insect societies: Optimal killing rates and the ambivalent effect of high social interaction rates
VL - 372
ER -
TY - JOUR
AB - We consider mating strategies for females who search for males sequentially during a season of limited length. We show that the best strategy rejects a given male type if encountered before a time-threshold but accepts him after. For frequency-independent benefits, we obtain the optimal time-thresholds explicitly for both discrete and continuous distributions of males, and allow for mistakes being made in assessing the correct male type. When the benefits are indirect (genes for the offspring) and the population is under frequency-dependent ecological selection, the benefits depend on the mating strategy of other females as well. This case is particularly relevant to speciation models that seek to explore the stability of reproductive isolation by assortative mating under frequency-dependent ecological selection. We show that the indirect benefits are to be quantified by the reproductive values of couples, and describe how the evolutionarily stable time-thresholds can be found. We conclude with an example based on the Levene model, in which we analyze the evolutionarily stable assortative mating strategies and the strength of reproductive isolation provided by them.
AU - Priklopil, Tadeas
AU - Kisdi, Eva
AU - Gyllenberg, Mats
ID - 1851
IS - 4
JF - Evolution
TI - Evolutionarily stable mating decisions for sequentially searching females and the stability of reproductive isolation by assortative mating
VL - 69
ER -
TY - JOUR
AB - Summary: Declining populations of bee pollinators are a cause of concern, with major repercussions for biodiversity loss and food security. RNA viruses associated with honeybees represent a potential threat to other insect pollinators, but the extent of this threat is poorly understood. This study aims to attain a detailed understanding of the current and ongoing risk of emerging infectious disease (EID) transmission between managed and wild pollinator species across a wide range of RNA viruses. Within a structured large-scale national survey across 26 independent sites, we quantify the prevalence and pathogen loads of multiple RNA viruses in co-occurring managed honeybee (Apis mellifera) and wild bumblebee (Bombus spp.) populations. We then construct models that compare virus prevalence between wild and managed pollinators. Multiple RNA viruses associated with honeybees are widespread in sympatric wild bumblebee populations. Virus prevalence in honeybees is a significant predictor of virus prevalence in bumblebees, but we remain cautious in speculating over the principle direction of pathogen transmission. We demonstrate species-specific differences in prevalence, indicating significant variation in disease susceptibility or tolerance. Pathogen loads within individual bumblebees may be high and in the case of at least one RNA virus, prevalence is higher in wild bumblebees than in managed honeybee populations. Our findings indicate widespread transmission of RNA viruses between managed and wild bee pollinators, pointing to an interconnected network of potential disease pressures within and among pollinator species. In the context of the biodiversity crisis, our study emphasizes the importance of targeting a wide range of pathogens and defining host associations when considering potential drivers of population decline.
AU - Mcmahon, Dino
AU - Fürst, Matthias
AU - Caspar, Jesicca
AU - Theodorou, Panagiotis
AU - Brown, Mark
AU - Paxton, Robert
ID - 1855
IS - 3
JF - Journal of Animal Ecology
TI - A sting in the spit: Widespread cross-infection of multiple RNA viruses across wild and managed bees
VL - 84
ER -
TY - JOUR
AB - The traditional synthesis question given a specification asks for the automatic construction of a system that satisfies the specification, whereas often there exists a preference order among the different systems that satisfy the given specification. Under a probabilistic assumption about the possible inputs, such a preference order is naturally expressed by a weighted automaton, which assigns to each word a value, such that a system is preferred if it generates a higher expected value. We solve the following optimal synthesis problem: given an omega-regular specification, a Markov chain that describes the distribution of inputs, and a weighted automaton that measures how well a system satisfies the given specification under the input assumption, synthesize a system that optimizes the measured value. For safety specifications and quantitative measures that are defined by mean-payoff automata, the optimal synthesis problem reduces to finding a strategy in a Markov decision process (MDP) that is optimal for a long-run average reward objective, which can be achieved in polynomial time. For general omega-regular specifications along with mean-payoff automata, the solution rests on a new, polynomial-time algorithm for computing optimal strategies in MDPs with mean-payoff parity objectives. Our algorithm constructs optimal strategies that consist of two memoryless strategies and a counter. The counter is in general not bounded. To obtain a finite-state system, we show how to construct an ε-optimal strategy with a bounded counter, for all ε > 0. Furthermore, we show how to decide in polynomial time if it is possible to construct an optimal finite-state system (i.e., a system without a counter) for a given specification. We have implemented our approach and the underlying algorithms in a tool that takes qualitative and quantitative specifications and automatically constructs a system that satisfies the qualitative specification and optimizes the quantitative specification, if such a system exists. We present some experimental results showing optimal systems that were automatically generated in this way.
AU - Chatterjee, Krishnendu
AU - Henzinger, Thomas A
AU - Jobstmann, Barbara
AU - Singh, Rohit
ID - 1856
IS - 1
JF - Journal of the ACM
TI - Measuring and synthesizing systems in probabilistic environments
VL - 62
ER -
TY - CONF
AB - Sharing information between multiple tasks enables algorithms to achieve good generalization performance even from small amounts of training data. However, in a realistic scenario of multi-task learning not all tasks are equally related to each other, hence it could be advantageous to transfer information only between the most related tasks. In this work we propose an approach that processes multiple tasks in a sequence with sharing between subsequent tasks instead of solving all tasks jointly. Subsequently, we address the question of curriculum learning of tasks, i.e. finding the best order of tasks to be learned. Our approach is based on a generalization bound criterion for choosing the task order that optimizes the average expected classification performance over all tasks. Our experimental results show that learning multiple related tasks sequentially can be more effective than learning them jointly, the order in which tasks are being solved affects the overall performance, and that our model is able to automatically discover the favourable order of tasks.
AU - Pentina, Anastasia
AU - Sharmanska, Viktoriia
AU - Lampert, Christoph
ID - 1857
TI - Curriculum learning of multiple tasks
ER -
TY - CONF
AB - We study the problem of predicting the future, though only in the probabilistic sense of estimating a future state of a time-varying probability distribution. This is not only an interesting academic problem, but solving this extrapolation problem also has many practical application, e.g. for training classifiers that have to operate under time-varying conditions. Our main contribution is a method for predicting the next step of the time-varying distribution from a given sequence of sample sets from earlier time steps. For this we rely on two recent machine learning techniques: embedding probability distributions into a reproducing kernel Hilbert space, and learning operators by vector-valued regression. We illustrate the working principles and the practical usefulness of our method by experiments on synthetic and real data. We also highlight an exemplary application: training a classifier in a domain adaptation setting without having access to examples from the test time distribution at training time.
AU - Lampert, Christoph
ID - 1858
TI - Predicting the future behavior of a time-varying probability distribution
ER -
TY - CONF
AB - Structural support vector machines (SSVMs) are amongst the best performing models for structured computer vision tasks, such as semantic image segmentation or human pose estimation. Training SSVMs, however, is computationally costly, because it requires repeated calls to a structured prediction subroutine (called \emph{max-oracle}), which has to solve an optimization problem itself, e.g. a graph cut.
In this work, we introduce a new algorithm for SSVM training that is more efficient than earlier techniques when the max-oracle is computationally expensive, as it is frequently the case in computer vision tasks. The main idea is to (i) combine the recent stochastic Block-Coordinate Frank-Wolfe algorithm with efficient hyperplane caching, and (ii) use an automatic selection rule for deciding whether to call the exact max-oracle or to rely on an approximate one based on the cached hyperplanes.
We show experimentally that this strategy leads to faster convergence to the optimum with respect to the number of requires oracle calls, and that this translates into faster convergence with respect to the total runtime when the max-oracle is slow compared to the other steps of the algorithm.
AU - Shah, Neel
AU - Kolmogorov, Vladimir
AU - Lampert, Christoph
ID - 1859
TI - A multi-plane block-coordinate Frank-Wolfe algorithm for training structural SVMs with a costly max-oracle
ER -
TY - CONF
AB - Classifiers for object categorization are usually evaluated by their accuracy on a set of i.i.d. test examples. This provides us with an estimate of the expected error when applying the classifiers to a single new image. In real application, however, classifiers are rarely only used for a single image and then discarded. Instead, they are applied sequentially to many images, and these are typically not i.i.d. samples from a fixed data distribution, but they carry dependencies and their class distribution varies over time. In this work, we argue that the phenomenon of correlated data at prediction time is not a nuisance, but a blessing in disguise. We describe a probabilistic method for adapting classifiers at prediction time without having to retrain them. We also introduce a framework for creating realistically distributed image sequences, which offers a way to benchmark classifier adaptation methods, such as the one we propose. Experiments on the ILSVRC2010 and ILSVRC2012 datasets show that adapting object classification systems at prediction time can significantly reduce their error rate, even with no additional human feedback.
AU - Royer, Amélie
AU - Lampert, Christoph
ID - 1860
TI - Classifier adaptation at prediction time
ER -
TY - JOUR
AB - Continuous-time Markov chains are commonly used in practice for modeling biochemical reaction networks in which the inherent randomness of themolecular interactions cannot be ignored. This has motivated recent research effort into methods for parameter inference and experiment design for such models. The major difficulty is that such methods usually require one to iteratively solve the chemical master equation that governs the time evolution of the probability distribution of the system. This, however, is rarely possible, and even approximation techniques remain limited to relatively small and simple systems. An alternative explored in this article is to base methods on only some low-order moments of the entire probability distribution. We summarize the theory behind such moment-based methods for parameter inference and experiment design and provide new case studies where we investigate their performance.
AU - Ruess, Jakob
AU - Lygeros, John
ID - 1861
IS - 2
JF - ACM Transactions on Modeling and Computer Simulation
TI - Moment-based methods for parameter inference and experiment design for stochastic biochemical reaction networks
VL - 25
ER -
TY - JOUR
AB - The Altshuler–Shklovskii formulas (Altshuler and Shklovskii, BZh Eksp Teor Fiz 91:200, 1986) predict, for any disordered quantum system in the diffusive regime, a universal power law behaviour for the correlation functions of the mesoscopic eigenvalue density. In this paper and its companion (Erdős and Knowles, The Altshuler–Shklovskii formulas for random band matrices I: the unimodular case, 2013), we prove these formulas for random band matrices. In (Erdős and Knowles, The Altshuler–Shklovskii formulas for random band matrices I: the unimodular case, 2013) we introduced a diagrammatic approach and presented robust estimates on general diagrams under certain simplifying assumptions. In this paper, we remove these assumptions by giving a general estimate of the subleading diagrams. We also give a precise analysis of the leading diagrams which give rise to the Altschuler–Shklovskii power laws. Moreover, we introduce a family of general random band matrices which interpolates between real symmetric (β = 1) and complex Hermitian (β = 2) models, and track the transition for the mesoscopic density–density correlation. Finally, we address the higher-order correlation functions by proving that they behave asymptotically according to a Gaussian process whose covariance is given by the Altshuler–Shklovskii formulas.
AU - Erdös, László
AU - Knowles, Antti
ID - 1864
IS - 3
JF - Annales Henri Poincare
TI - The Altshuler–Shklovskii formulas for random band matrices II: The general case
VL - 16
ER -
TY - JOUR
AB - The plant hormone auxin and its directional transport are known to play a crucial role in defining the embryonic axis and subsequent development of the body plan. Although the role of PIN auxin efflux transporters has been clearly assigned during embryonic shoot and root specification, the role of the auxin influx carriers AUX1 and LIKE-AUX1 (LAX) proteins is not well established. Here, we used chemical and genetic tools on Brassica napus microspore-derived embryos and Arabidopsis thaliana zygotic embryos, and demonstrate that AUX1, LAX1 and LAX2 are required for both shoot and root pole formation, in concert with PIN efflux carriers. Furthermore, we uncovered a positive-feedback loop betweenMONOPTEROS(ARF5)-dependent auxin signalling and auxin transport. ThisMONOPTEROSdependent transcriptional regulation of auxin influx (AUX1, LAX1 and LAX2) and auxin efflux (PIN1 and PIN4) carriers by MONOPTEROS helps to maintain proper auxin transport to the root tip. These results indicate that auxin-dependent cell specification during embryo development requires balanced auxin transport involving both influx and efflux mechanisms, and that this transport is maintained by a positive transcriptional feedback on auxin signalling.
AU - Robert, Hélène
AU - Grunewald, Wim
AU - Sauer, Michael
AU - Cannoot, Bernard
AU - Soriano, Mercedes
AU - Swarup, Ranjan
AU - Weijers, Dolf
AU - Bennett, Malcolm
AU - Boutilier, Kim
AU - Friml, Jirí
ID - 1865
IS - 4
JF - Development
TI - Plant embryogenesis requires AUX/LAX-mediated auxin influx
VL - 142
ER -
TY - JOUR
AU - Henzinger, Thomas A
AU - Raskin, Jean
ID - 1866
IS - 2
JF - Communications of the ACM
TI - The equivalence problem for finite automata: Technical perspective
VL - 58
ER -
TY - JOUR
AB - Cultured mammalian cells essential are model systems in basic biology research, production platforms of proteins for medical use, and testbeds in synthetic biology. Flavin cofactors, in particular flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), are critical for cellular redox reactions and sense light in naturally occurring photoreceptors and optogenetic tools. Here, we quantified flavin contents of commonly used mammalian cell lines. We first compared three procedures for extraction of free and noncovalently protein-bound flavins and verified extraction using fluorescence spectroscopy. For separation, two CE methods with different BGEs were established, and detection was performed by LED-induced fluorescence with limit of detections (LODs 0.5-3.8 nM). We found that riboflavin (RF), FMN, and FAD contents varied significantly between cell lines. RF (3.1-14 amol/cell) and FAD (2.2-17.0 amol/cell) were the predominant flavins, while FMN (0.46-3.4 amol/cell) was found at markedly lower levels. Observed flavin contents agree with those previously extracted from mammalian tissues, yet reduced forms of RF were detected that were not described previously. Quantification of flavins in mammalian cell lines will allow a better understanding of cellular redox reactions and optogenetic tools.
AU - Hühner, Jens
AU - Inglés Prieto, Álvaro
AU - Neusüß, Christian
AU - Lämmerhofer, Michael
AU - Janovjak, Harald L
ID - 1867
IS - 4
JF - Electrophoresis
TI - Quantification of riboflavin, flavin mononucleotide, and flavin adenine dinucleotide in mammalian model cells by CE with LED-induced fluorescence detection
VL - 36
ER -
TY - JOUR
AB - We investigate high-dimensional nonlinear dynamical systems exhibiting multiple resonances under adiabatic parameter variations. Our motivations come from experimental considerations where time-dependent sweeping of parameters is a practical approach to probing and characterizing the bifurcations of the system. The question is whether bifurcations so detected are faithful representations of the bifurcations intrinsic to the original stationary system. Utilizing a harmonically forced, closed fluid flow system that possesses multiple resonances and solving the Navier-Stokes equation under proper boundary conditions, we uncover the phenomenon of the early effect. Specifically, as a control parameter, e.g., the driving frequency, is adiabatically increased from an initial value, resonances emerge at frequency values that are lower than those in the corresponding stationary system. The phenomenon is established by numerical characterization of physical quantities through the resonances, which include the kinetic energy and the vorticity field, and a heuristic analysis based on the concept of instantaneous frequency. A simple formula is obtained which relates the resonance points in the time-dependent and time-independent systems. Our findings suggest that, in general, any true bifurcation of a nonlinear dynamical system can be unequivocally uncovered through adiabatic parameter sweeping, in spite of a shift in the bifurcation point, which is of value to experimental studies of nonlinear dynamical systems.
AU - Park, Youngyong
AU - Do, Younghae
AU - Altmeyer, Sebastian
AU - Lai, Yingcheng
AU - Lee, Gyuwon
ID - 1868
IS - 2
JF - Physical Review E
SN - 1539-3755
TI - Early effect in time-dependent, high-dimensional nonlinear dynamical systems with multiple resonances
VL - 91
ER -
TY - JOUR
AB - The plant hormone auxin is a key regulator of plant growth and development. Differences in auxin distribution within tissues are mediated by the polar auxin transport machinery, and cellular auxin responses occur depending on changes in cellular auxin levels. Multiple receptor systems at the cell surface and in the interior operate to sense and interpret fluctuations in auxin distribution that occur during plant development. Until now, three proteins or protein complexes that can bind auxin have been identified. SCFTIR1 [a SKP1-cullin-1-F-box complex that contains transport inhibitor response 1 (TIR1) as the F-box protein] and S-phase-kinaseassociated protein 2 (SKP2) localize to the nucleus, whereas auxinbinding protein 1 (ABP1), predominantly associates with the endoplasmic reticulum and cell surface. In this Cell Science at a Glance article, we summarize recent discoveries in the field of auxin transport and signaling that have led to the identification of new components of these pathways, as well as their mutual interaction.
AU - Grones, Peter
AU - Friml, Jirí
ID - 1871
IS - 1
JF - Journal of Cell Science
TI - Auxin transporters and binding proteins at a glance
VL - 128
ER -
TY - JOUR
AB - We consider partially observable Markov decision processes (POMDPs) with limit-average payoff, where a reward value in the interval [0,1] is associated with every transition, and the payoff of an infinite path is the long-run average of the rewards. We consider two types of path constraints: (i) a quantitative constraint defines the set of paths where the payoff is at least a given threshold λ1ε(0,1]; and (ii) a qualitative constraint which is a special case of the quantitative constraint with λ1=1. We consider the computation of the almost-sure winning set, where the controller needs to ensure that the path constraint is satisfied with probability 1. Our main results for qualitative path constraints are as follows: (i) the problem of deciding the existence of a finite-memory controller is EXPTIME-complete; and (ii) the problem of deciding the existence of an infinite-memory controller is undecidable. For quantitative path constraints we show that the problem of deciding the existence of a finite-memory controller is undecidable. We also present a prototype implementation of our EXPTIME algorithm and experimental results on several examples.
AU - Chatterjee, Krishnendu
AU - Chmelik, Martin
ID - 1873
JF - Artificial Intelligence
TI - POMDPs under probabilistic semantics
VL - 221
ER -
TY - JOUR
AB - The hippocampal region, comprising the hippocampal formation and the parahippocampal region, has been one of the most intensively studied parts of the brain for decades. Better understanding of its functional diversity and complexity has led to an increased demand for specificity in experimental procedures and manipulations. In view of the complex 3D structure of the hippocampal region, precisely positioned experimental approaches require a fine-grained architectural description that is available and readable to experimentalists lacking detailed anatomical experience. In this paper, we provide the first cyto- and chemoarchitectural description of the hippocampal formation and parahippocampal region in the rat at high resolution and in the three standard sectional planes: coronal, horizontal and sagittal. The atlas uses a series of adjacent sections stained for neurons and for a number of chemical marker substances, particularly parvalbumin and calbindin. All the borders defined in one plane have been cross-checked against their counterparts in the other two planes. The entire dataset will be made available as a web-based interactive application through the Rodent Brain WorkBench (http://www.rbwb.org) which, together with this paper, provides a unique atlas resource.
AU - Boccara, Charlotte
AU - Kjønigsen, Lisa
AU - Hammer, Ingvild
AU - Bjaalie, Jan
AU - Leergaard, Trygve
AU - Witter, Menno
ID - 1874
IS - 7
JF - Hippocampus
TI - A three-plane architectonic atlas of the rat hippocampal region
VL - 25
ER -
TY - JOUR
AB - Petrocoptis is a small genus of chasmophytic plants endemic to the Iberian Peninsula, with some localized populations in the French Pyrenees. Within the genus, a dozen species have been recognized based on morphological diversity, most of them with limited distribution area, in small populations and frequently with potential threats to their survival. To date, however, a molecular evaluation of the current systematic treatments has not been carried out. The aim of the present study is to infer phylogenetic relationships among its subordinate taxa by using plastidial rps16 intron and nuclear internal transcribed spacer (ITS) DNA sequences; and evaluate the phylogenetic placement of the genus Petrocoptis within the family Caryophyllaceae. The monophyly of Petrocoptis is supported by both ITS and rps16 intron sequence analyses. Furthermore, time estimates using BEAST analyses indicate a Middle to Late Miocene diversification (10.59 Myr, 6.44–15.26 Myr highest posterior densities [HPD], for ITS; 14.30 Myr, 8.61–21.00 Myr HPD, for rps16 intron).
AU - Cires Rodriguez, Eduardo
AU - Prieto, José
ID - 1878
IS - 2
JF - Journal of Plant Research
TI - Phylogenetic relationships of Petrocoptis A. Braun ex Endl. (Caryophyllaceae), a discussed genus from the Iberian Peninsula
VL - 128
ER -
TY - JOUR
AB - When electron microscopy (EM) was introduced in the 1930s it gave scientists their first look into the nanoworld of cells. Over the last 80 years EM has vastly increased our understanding of the complex cellular structures that underlie the diverse functions that cells need to maintain life. One drawback that has been difficult to overcome was the inherent lack of volume information, mainly due to the limit on the thickness of sections that could be viewed in a transmission electron microscope (TEM). For many years scientists struggled to achieve three-dimensional (3D) EM using serial section reconstructions, TEM tomography, and scanning EM (SEM) techniques such as freeze-fracture. Although each technique yielded some special information, they required a significant amount of time and specialist expertise to obtain even a very small 3D EM dataset. Almost 20 years ago scientists began to exploit SEMs to image blocks of embedded tissues and perform serial sectioning of these tissues inside the SEM chamber. Using first focused ion beams (FIB) and subsequently robotic ultramicrotomes (serial block-face, SBF-SEM) microscopists were able to collect large volumes of 3D EM information at resolutions that could address many important biological questions, and do so in an efficient manner. We present here some examples of 3D EM taken from the many diverse specimens that have been imaged in our core facility. We propose that the next major step forward will be to efficiently correlate functional information obtained using light microscopy (LM) with 3D EM datasets to more completely investigate the important links between cell structures and their functions.
AU - Kremer, A
AU - Lippens, Stefaan
AU - Bartunkova, Sonia
AU - Asselbergh, Bob
AU - Blanpain, Cendric
AU - Fendrych, Matyas
AU - Goossens, A
AU - Holt, Matthew
AU - Janssens, Sophie
AU - Krols, Michiel
AU - Larsimont, Jean
AU - Mc Guire, Conor
AU - Nowack, Moritz
AU - Saelens, Xavier
AU - Schertel, Andreas
AU - Schepens, B
AU - Slezak, M
AU - Timmerman, Vincent
AU - Theunis, Clara
AU - Van Brempt, Ronald
AU - Visser, Y
AU - Guérin, Christophe
ID - 1879
IS - 2
JF - Journal of Microscopy
TI - Developing 3D SEM in a broad biological context
VL - 259
ER -
TY - JOUR
AB - We investigate the relation between Bose-Einstein condensation (BEC) and superfluidity in the ground state of a one-dimensional model of interacting bosons in a strong random potential. We prove rigorously that in a certain parameter regime the superfluid fraction can be arbitrarily small while complete BEC prevails. In another regime there is both complete BEC and complete superfluidity, despite the strong disorder
AU - Könenberg, Martin
AU - Moser, Thomas
AU - Seiringer, Robert
AU - Yngvason, Jakob
ID - 1880
JF - New Journal of Physics
TI - Superfluid behavior of a Bose-Einstein condensate in a random potential
VL - 17
ER -
TY - CONF
AB - We provide a framework for compositional and iterative design and verification of systems with quantitative information, such as rewards, time or energy. It is based on disjunctive modal transition systems where we allow actions to bear various types of quantitative information. Throughout the design process the actions can be further refined and the information made more precise. We show how to compute the results of standard operations on the systems, including the quotient (residual), which has not been previously considered for quantitative non-deterministic systems. Our quantitative framework has close connections to the modal nu-calculus and is compositional with respect to general notions of distances between systems and the standard operations.
AU - Fahrenberg, Uli
AU - Kretinsky, Jan
AU - Legay, Axel
AU - Traonouez, Louis
ID - 1882
TI - Compositionality for quantitative specifications
VL - 8997
ER -
TY - JOUR
AB - We introduce a one-parametric family of tree growth models, in which branching probabilities decrease with branch age τ as τ-α. Depending on the exponent α, the scaling of tree depth with tree size n displays a transition between the logarithmic scaling of random trees and an algebraic growth. At the transition (α=1) tree depth grows as (logn)2. This anomalous scaling is in good agreement with the trend observed in evolution of biological species, thus providing a theoretical support for age-dependent speciation and associating it to the occurrence of a critical point.
AU - Keller-Schmidt, Stephanie
AU - Tugrul, Murat
AU - Eguíluz, Víctor
AU - Hernandez Garcia, Emilio
AU - Klemm, Konstantin
ID - 1883
IS - 2
JF - Physical Review E Statistical Nonlinear and Soft Matter Physics
TI - Anomalous scaling in an age-dependent branching model
VL - 91
ER -
TY - JOUR
AB - The concept of positional information is central to our understanding of how cells determine their location in a multicellular structure and thereby their developmental fates. Nevertheless, positional information has neither been defined mathematically nor quantified in a principled way. Here we provide an information-theoretic definition in the context of developmental gene expression patterns and examine the features of expression patterns that affect positional information quantitatively. We connect positional information with the concept of positional error and develop tools to directly measure information and error from experimental data. We illustrate our framework for the case of gap gene expression patterns in the early Drosophila embryo and show how information that is distributed among only four genes is sufficient to determine developmental fates with nearly single-cell resolution. Our approach can be generalized to a variety of different model systems; procedures and examples are discussed in detail.
AU - Tkacik, Gasper
AU - Dubuis, Julien
AU - Petkova, Mariela
AU - Gregor, Thomas
ID - 1885
IS - 1
JF - Genetics
TI - Positional information, positional error, and readout precision in morphogenesis: A mathematical framework
VL - 199
ER -
TY - JOUR
AB - We numerically investigate the distribution of extrema of 'chaotic' Laplacian eigenfunctions on two-dimensional manifolds. Our contribution is two-fold: (a) we count extrema on grid graphs with a small number of randomly added edges and show the behavior to coincide with the 1957 prediction of Longuet-Higgins for the continuous case and (b) we compute the regularity of their spatial distribution using discrepancy, which is a classical measure from the theory of Monte Carlo integration. The first part suggests that grid graphs with randomly added edges should behave like two-dimensional surfaces with ergodic geodesic flow; in the second part we show that the extrema are more regularly distributed in space than the grid Z2.
AU - Pausinger, Florian
AU - Steinerberger, Stefan
ID - 1938
IS - 6
JF - Physics Letters, Section A
TI - On the distribution of local extrema in quantum chaos
VL - 379
ER -
TY - JOUR
AU - Dereziński, Jan
AU - Napiórkowski, Marcin M
ID - 1939
IS - 7
JF - Annales Henri Poincare
TI - Erratum to: Excitation spectrum of interacting bosons in the Mean-Field Infinite-Volume limit
VL - 16
ER -
TY - JOUR
AB - We typically think of cells as responding to external signals independently by regulating their gene expression levels, yet they often locally exchange information and coordinate. Can such spatial coupling be of benefit for conveying signals subject to gene regulatory noise? Here we extend our information-theoretic framework for gene regulation to spatially extended systems. As an example, we consider a lattice of nuclei responding to a concentration field of a transcriptional regulator (the "input") by expressing a single diffusible target gene. When input concentrations are low, diffusive coupling markedly improves information transmission; optimal gene activation functions also systematically change. A qualitatively new regulatory strategy emerges where individual cells respond to the input in a nearly step-like fashion that is subsequently averaged out by strong diffusion. While motivated by early patterning events in the Drosophila embryo, our framework is generically applicable to spatially coupled stochastic gene expression models.
AU - Sokolowski, Thomas R
AU - Tkacik, Gasper
ID - 1940
IS - 6
JF - Physical Review E Statistical Nonlinear and Soft Matter Physics
TI - Optimizing information flow in small genetic networks. IV. Spatial coupling
VL - 91
ER -
TY - JOUR
AU - Rakusová, Hana
AU - Fendrych, Matyas
AU - Friml, Jirí
ID - 1944
IS - 2
JF - Current Opinion in Plant Biology
TI - Intracellular trafficking and PIN-mediated cell polarity during tropic responses in plants
VL - 23
ER -
TY - 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 - Human immunodeficiency virus type 1 (HIV-1) assembly proceeds in two stages. First, the 55 kilodalton viral Gag polyprotein assembles into a hexameric protein lattice at the plasma membrane of the infected cell, inducing budding and release of an immature particle. Second, Gag is cleaved by the viral protease, leading to internal rearrangement of the virus into the mature, infectious form. Immature and mature HIV-1 particles are heterogeneous in size and morphology, preventing high-resolution analysis of their protein arrangement in situ by conventional structural biology methods. Here we apply cryo-electron tomography and sub-tomogram averaging methods to resolve the structure of the capsid lattice within intact immature HIV-1 particles at subnanometre resolution, allowing unambiguous positioning of all Î±-helices. The resulting model reveals tertiary and quaternary structural interactions that mediate HIV-1 assembly. Strikingly, these interactions differ from those predicted by the current model based on in vitro-assembled arrays of Gag-derived proteins from Mason-Pfizer monkey virus. To validate this difference, we solve the structure of the capsid lattice within intact immature Mason-Pfizer monkey virus particles. Comparison with the immature HIV-1 structure reveals that retroviral capsid proteins, while having conserved tertiary structures, adopt different quaternary arrangements during virus assembly. The approach demonstrated here should be applicable to determine structures of other proteins at subnanometre resolution within heterogeneous environments.
AU - Florian Schur
AU - Hagen, Wim J
AU - Rumlová, Michaela
AU - Ruml, Tomáš
AU - Müller B
AU - Kraüsslich, Hans Georg
AU - Briggs, John A
ID - 814
IS - 7535
JF - Nature
TI - Structure of the immature HIV-1 capsid in intact virus particles at 8.8 Å resolution
VL - 517
ER -
TY - JOUR
AB - The polyprotein Gag is the primary structural component of retroviruses. Gag consists of independently folded domains connected by flexible linkers. Interactions between the conserved capsid (CA) domains of Gag mediate formation of hexameric protein lattices that drive assembly of immature virus particles. Proteolytic cleavage of Gag by the viral protease (PR) is required for maturation of retroviruses from an immature form into an infectious form. Within the assembled Gag lattices of HIV-1 and Mason- Pfizer monkey virus (M-PMV), the C-terminal domain of CA adopts similar quaternary arrangements, while the N-terminal domain of CA is packed in very different manners. Here, we have used cryo-electron tomography and subtomogram averaging to study in vitro-assembled, immature virus-like Rous sarcoma virus (RSV) Gag particles and have determined the structure of CA and the surrounding regions to a resolution of ~8 Å. We found that the C-terminal domain of RSV CA is arranged similarly to HIV-1 and M-PMV, whereas the N-terminal domain of CA adopts a novel arrangement in which the upstream p10 domain folds back into the CA lattice. In this position the cleavage site between CA and p10 appears to be inaccessible to PR. Below CA, an extended density is consistent with the presence of a six-helix bundle formed by the spacer-peptide region. We have also assessed the affect of lattice assembly on proteolytic processing by exogenous PR. The cleavage between p10 and CA is indeed inhibited in the assembled lattice, a finding consistent with structural regulation of proteolytic maturation.
AU - Schur, Florian
AU - Dick, Robert
AU - Hagen, Wim
AU - Vogt, Volker
AU - Briggs, John
ID - 815
IS - 20
JF - Journal of Virology
TI - The structure of immature virus like Rous sarcoma virus gag particles reveals a structural role for the p10 domain in assembly
VL - 89
ER -
TY - GEN
AB - We study conditions under which a finite simplicial complex $K$ can be mapped to $\mathbb R^d$ without higher-multiplicity intersections. An almost $r$-embedding is a map $f: K\to \mathbb R^d$ such that the images of any $r$
pairwise disjoint simplices of $K$ do not have a common point. We show that if $r$ is not a prime power and $d\geq 2r+1$, then there is a counterexample to the topological Tverberg conjecture, i.e., there is an almost $r$-embedding of
the $(d+1)(r-1)$-simplex in $\mathbb R^d$. This improves on previous constructions of counterexamples (for $d\geq 3r$) based on a series of papers by M. \"Ozaydin, M. Gromov, P. Blagojevi\'c, F. Frick, G. Ziegler, and the second and fourth present authors. The counterexamples are obtained by proving the following algebraic criterion in codimension 2: If $r\ge3$ and if $K$ is a finite $2(r-1)$-complex then there exists an almost $r$-embedding $K\to \mathbb R^{2r}$ if and only if there exists a general position PL map $f:K\to \mathbb R^{2r}$ such that the algebraic intersection number of the $f$-images of any $r$ pairwise disjoint simplices of $K$ is zero. This result can be restated in terms of cohomological obstructions or equivariant maps, and extends an analogous codimension 3 criterion by the second and fourth authors. As another application we classify ornaments $f:S^3 \sqcup S^3\sqcup S^3\to \mathbb R^5$ up to ornament
concordance. It follows from work of M. Freedman, V. Krushkal and P. Teichner that the analogous criterion for $r=2$ is false. We prove a lemma on singular higher-dimensional Borromean rings, yielding an elementary proof of the counterexample.
AU - Avvakumov, Sergey
AU - Mabillard, Isaac
AU - Skopenkov, A.
AU - Wagner, Uli
ID - 8183
TI - Eliminating higher-multiplicity intersections, III. Codimension 2
ER -
TY - JOUR
AU - Einhorn, Lukas
AU - Fazekas, Judit
AU - Muhr, Martina
AU - Schoos, Alexandra
AU - Oida, Kumiko
AU - Singer, Josef
AU - Panakova, Lucia
AU - Manzano-Szalai, Krisztina
AU - Jensen-Jarolim, Erika
ID - 8242
IS - 2
JF - Journal of Allergy and Clinical Immunology
SN - 0091-6749
TI - Generation of recombinant FcεRIα of dog, cat and horse for component-resolved allergy diagnosis in veterinary patients
VL - 135
ER -
TY - JOUR
AB - Plants maintain capacity to form new organs such as leaves, flowers, lateral shoots and roots throughout their postembryonic lifetime. Lateral roots (LRs) originate from a few pericycle cells that acquire attributes of founder cells (FCs), undergo series of anticlinal divisions, and give rise to a few short initial cells. After initiation, coordinated cell division and differentiation occur, giving rise to lateral root primordia (LRP). Primordia continue to grow, emerge through the cortex and epidermal layers of the primary root, and finally a new apical meristem is established taking over the responsibility for growth of mature lateral roots [for detailed description of the individual stages of lateral root organogenesis see Malamy and Benfey (1997)]. To examine this highly dynamic developmental process and to investigate a role of various hormonal, genetic and environmental factors in the regulation of lateral root organogenesis, the real time imaging based analyses represent extremely powerful tools (Laskowski et al., 2008; De Smet et al., 2012; Marhavy et al., 2013 and 2014). Herein, we describe a protocol for real time lateral root primordia (LRP) analysis, which enables the monitoring of an onset of the specific gene expression and subcellular protein localization during primordia organogenesis, as well as the evaluation of the impact of genetic and environmental perturbations on LRP organogenesis.
AU - Peter Marhavy
AU - Eva Benková
ID - 832
IS - 8
JF - Bio-protocol
TI - Real time analysis of lateral root organogenesis in arabidopsis
VL - 5
ER -
TY - JOUR
AB - The nature of factors governing the tempo and mode of protein evolution is a fundamental issue in evolutionary biology. Specifically, whether or not interactions between different sites, or epistasis, are important in directing the course of evolution became one of the central questions. Several recent reports have scrutinized patterns of long-term protein evolution claiming them to be compatible only with an epistatic fitness landscape. However, these claims have not yet been substantiated with a formal model of protein evolution. Here, we formulate a simple covarion-like model of protein evolution focusing on the rate at which the fitness impact of amino acids at a site changes with time. We then apply the model to the data on convergent and divergent protein evolution to test whether or not the incorporation of epistatic interactions is necessary to explain the data. We find that convergent evolution cannot be explained without the incorporation of epistasis and the rate at which an amino acid state switches from being acceptable at a site to being deleterious is faster than the rate of amino acid substitution. Specifically, for proteins that have persisted in modern prokaryotic organisms since the last universal common ancestor for one amino acid substitution approximately ten amino acid states switch from being accessible to being deleterious, or vice versa. Thus, molecular evolution can only be perceived in the context of rapid turnover of which amino acids are available for evolution.
AU - Usmanova, Dinara
AU - Ferretti, Luca
AU - Povolotskaya, Inna
AU - Vlasov, Peter
AU - Kondrashov, Fyodor
ID - 848
IS - 2
JF - Molecular Biology and Evolution
TI - A model of substitution trajectories in sequence space and long-term protein evolution
VL - 32
ER -
TY - JOUR
AB - Proteases play important roles in many biologic processes and are key mediators of cancer, inflammation, and thrombosis. However, comprehensive and quantitative techniques to define the substrate specificity profile of proteases are lacking. The metalloprotease ADAMTS13 regulates blood coagulation by cleaving von Willebrand factor (VWF), reducing its procoagulant activity. A mutagenized substrate phage display library based on a 73-amino acid fragment of VWF was constructed, and the ADAMTS13-dependent change in library complexity was evaluated over reaction time points, using high-throughput sequencing. Reaction rate constants (kcat/KM) were calculated for nearly every possible single amino acid substitution within this fragment. This massively parallel enzyme kinetics analysis detailed the specificity of ADAMTS13 and demonstrated the critical importance of the P1-P1' substrate residues while defining exosite binding domains. These data provided empirical evidence for the propensity for epistasis within VWF and showed strong correlation to conservation across orthologs, highlighting evolutionary selective pressures for VWF.
AU - Kretz, Colin A
AU - Dai, Manhong
AU - Soylemez, Onuralp
AU - Yee, Andrew
AU - Desch, Karl C
AU - Siemieniak, David R
AU - Tomberg, Kärt
AU - Fyodor Kondrashov
AU - Meng, Fan
AU - Ginsburg, David B
ID - 866
IS - 30
JF - PNAS
TI - Massively parallel enzyme kinetics reveals the substrate recognition landscape of the metalloprotease ADAMTS13
VL - 112
ER -