TY - CONF
AB - We study the pattern frequency vector for runs in probabilistic Vector Addition Systems with States (pVASS). Intuitively, each configuration of a given pVASS is assigned one of finitely many patterns, and every run can thus be seen as an infinite sequence of these patterns. The pattern frequency vector assigns to each run the limit of pattern frequencies computed for longer and longer prefixes of the run. If the limit does not exist, then the vector is undefined. We show that for one-counter pVASS, the pattern frequency vector is defined and takes one of finitely many values for almost all runs. Further, these values and their associated probabilities can be approximated up to an arbitrarily small relative error in polynomial time. For stable two-counter pVASS, we show the same result, but we do not provide any upper complexity bound. As a byproduct of our study, we discover counterexamples falsifying some classical results about stochastic Petri nets published in the 80s.
AU - Brázdil, Tomáš
AU - Kiefer, Stefan
AU - Kučera, Antonín
AU - Novotny, Petr
ID - 1660
TI - Long-run average behaviour of probabilistic vector addition systems
ER -
TY - JOUR
AB - Which genetic alterations drive tumorigenesis and how they evolve over the course of disease and therapy are central questions in cancer biology. Here we identify 44 recurrently mutated genes and 11 recurrent somatic copy number variations through whole-exome sequencing of 538 chronic lymphocytic leukaemia (CLL) and matched germline DNA samples, 278 of which were collected in a prospective clinical trial. These include previously unrecognized putative cancer drivers (RPS15, IKZF3), and collectively identify RNA processing and export, MYC activity, and MAPK signalling as central pathways involved in CLL. Clonality analysis of this large data set further enabled reconstruction of temporal relationships between driver events. Direct comparison between matched pre-treatment and relapse samples from 59 patients demonstrated highly frequent clonal evolution. Thus, large sequencing data sets of clinically informative samples enable the discovery of novel genes associated with cancer, the network of relationships between the driver events, and their impact on disease relapse and clinical outcome.
AU - Landau, Dan
AU - Tausch, Eugen
AU - Taylor Weiner, Amaro
AU - Stewart, Chip
AU - Reiter, Johannes
AU - Bahlo, Jasmin
AU - Kluth, Sandra
AU - Božić, Ivana
AU - Lawrence, Michael
AU - Böttcher, Sebastian
AU - Carter, Scott
AU - Cibulskis, Kristian
AU - Mertens, Daniel
AU - Sougnez, Carrie
AU - Rosenberg, Mara
AU - Hess, Julian
AU - Edelmann, Jennifer
AU - Kless, Sabrina
AU - Kneba, Michael
AU - Ritgen, Matthias
AU - Fink, Anna
AU - Fischer, Kirsten
AU - Gabriel, Stacey
AU - Lander, Eric
AU - Nowak, Martin
AU - Döhner, Hartmut
AU - Hallek, Michael
AU - Neuberg, Donna
AU - Getz, Gad
AU - Stilgenbauer, Stephan
AU - Wu, Catherine
ID - 1665
IS - 7574
JF - Nature
TI - Mutations driving CLL and their evolution in progression and relapse
VL - 526
ER -
TY - JOUR
AB - CREB-binding protein (CBP) and p300 are transcriptional coactivators involved in numerous biological processes that affect cell growth, transformation, differentiation, and development. In this study, we provide evidence of the involvement of homeodomain-interacting protein kinase 2 (HIPK2) in the regulation of CBP activity. We show that HIPK2 interacts with and phosphorylates several regions of CBP. We demonstrate that serines 2361, 2363, 2371, 2376, and 2381 are responsible for the HIPK2-induced mobility shift of CBP C-terminal activation domain. Moreover, we show that HIPK2 strongly potentiates the transcriptional activity of CBP. However, our data suggest that HIPK2 activates CBP mainly by counteracting the repressive action of cell cycle regulatory domain 1 (CRD1), located between amino acids 977 and 1076, independently of CBP phosphorylation. Our findings thus highlight a complex regulation of CBP activity by HIPK2, which might be relevant for the control of specific sets of target genes involved in cellular proliferation, differentiation and apoptosis.
AU - Kovács, Krisztián
AU - Steinmann, Myriam
AU - Halfon, Olivier
AU - Magistretti, Pierre
AU - Cardinaux, Jean
ID - 1663
IS - 11
JF - Cellular Signalling
TI - Complex regulation of CREB-binding protein by homeodomain-interacting protein kinase 2
VL - 27
ER -
TY - CONF
AB - We consider parametric version of fixed-delay continuoustime Markov chains (or equivalently deterministic and stochastic Petri nets, DSPN) where fixed-delay transitions are specified by parameters, rather than concrete values. Our goal is to synthesize values of these parameters that, for a given cost function, minimise expected total cost incurred before reaching a given set of target states. We show that under mild assumptions, optimal values of parameters can be effectively approximated using translation to a Markov decision process (MDP) whose actions correspond to discretized values of these parameters. To this end we identify and overcome several interesting phenomena arising in systems with fixed delays.
AU - Brázdil, Tomáš
AU - Korenčiak, L'Uboš
AU - Krčál, Jan
AU - Novotny, Petr
AU - Řehák, Vojtěch
ID - 1667
TI - Optimizing performance of continuous-time stochastic systems using timeout synthesis
VL - 9259
ER -
TY - JOUR
AB - Over a century of research into the origin of turbulence in wall-bounded shear flows has resulted in a puzzling picture in which turbulence appears in a variety of different states competing with laminar background flow. At moderate flow speeds, turbulence is confined to localized patches; it is only at higher speeds that the entire flow becomes turbulent. The origin of the different states encountered during this transition, the front dynamics of the turbulent regions and the transformation to full turbulence have yet to be explained. By combining experiments, theory and computer simulations, here we uncover a bifurcation scenario that explains the transformation to fully turbulent pipe flow and describe the front dynamics of the different states encountered in the process. Key to resolving this problem is the interpretation of the flow as a bistable system with nonlinear propagation (advection) of turbulent fronts. These findings bridge the gap between our understanding of the onset of turbulence and fully turbulent flows.
AU - Barkley, Dwight
AU - Song, Baofang
AU - Vasudevan, Mukund
AU - Lemoult, Grégoire M
AU - Avila, Marc
AU - Hof, Björn
ID - 1664
IS - 7574
JF - Nature
TI - The rise of fully turbulent flow
VL - 526
ER -
TY - CONF
AB - Composable notions of incoercibility aim to forbid a coercer from using anything beyond the coerced parties’ inputs and outputs to catch them when they try to deceive him. Existing definitions are restricted to weak coercion types, and/or are not universally composable. Furthermore, they often make too strong assumptions on the knowledge of coerced parties—e.g., they assume they known the identities and/or the strategies of other coerced parties, or those of corrupted parties— which makes them unsuitable for applications of incoercibility such as e-voting, where colluding adversarial parties may attempt to coerce honest voters, e.g., by offering them money for a promised vote, and use their own view to check that the voter keeps his end of the bargain. In this work we put forward the first universally composable notion of incoercible multi-party computation, which satisfies the above intuition and does not assume collusions among coerced parties or knowledge of the corrupted set. We define natural notions of UC incoercibility corresponding to standard coercion-types, i.e., receipt-freeness and resistance to full-active coercion. Importantly, our suggested notion has the unique property that it builds on top of the well studied UC framework by Canetti instead of modifying it. This guarantees backwards compatibility, and allows us to inherit results from the rich UC literature. We then present MPC protocols which realize our notions of UC incoercibility given access to an arguably minimal setup—namely honestly generate tamper-proof hardware performing a very simple cryptographic operation—e.g., a smart card. This is, to our knowledge, the first proposed construction of an MPC protocol (for more than two parties) that is incoercibly secure and universally composable, and therefore the first construction of a universally composable receipt-free e-voting protocol.
AU - Alwen, Joel F
AU - Ostrovsky, Rafail
AU - Zhou, Hongsheng
AU - Zikas, Vassilis
ID - 1672
SN - 978-3-662-47999-5
T2 - Advances in Cryptology - CRYPTO 2015
TI - Incoercible multi-party computation and universally composable receipt-free voting
VL - 9216
ER -
TY - CONF
AB - Computational notions of entropy (a.k.a. pseudoentropy) have found many applications, including leakage-resilient cryptography, deterministic encryption or memory delegation. The most important tools to argue about pseudoentropy are chain rules, which quantify by how much (in terms of quantity and quality) the pseudoentropy of a given random variable X decreases when conditioned on some other variable Z (think for example of X as a secret key and Z as information leaked by a side-channel). In this paper we give a very simple and modular proof of the chain rule for HILL pseudoentropy, improving best known parameters. Our version allows for increasing the acceptable length of leakage in applications up to a constant factor compared to the best previous bounds. As a contribution of independent interest, we provide a comprehensive study of all known versions of the chain rule, comparing their worst-case strength and limitations.
AU - Pietrzak, Krzysztof Z
AU - Skórski, Maciej
ID - 1669
TI - The chain rule for HILL pseudoentropy, revisited
VL - 9230
ER -
TY - CONF
AB - This paper studies the concrete security of PRFs and MACs obtained by keying hash functions based on the sponge paradigm. One such hash function is KECCAK, selected as NIST’s new SHA-3 standard. In contrast to other approaches like HMAC, the exact security of keyed sponges is not well understood. Indeed, recent security analyses delivered concrete security bounds which are far from existing attacks. This paper aims to close this gap. We prove (nearly) exact bounds on the concrete PRF security of keyed sponges using a random permutation. These bounds are tight for the most relevant ranges of parameters, i.e., for messages of length (roughly) l ≤ min{2n/4, 2r} blocks, where n is the state size and r is the desired output length; and for l ≤ q queries (to the construction or the underlying permutation). Moreover, we also improve standard-model bounds. As an intermediate step of independent interest, we prove tight bounds on the PRF security of the truncated CBC-MAC construction, which operates as plain CBC-MAC, but only returns a prefix of the output.
AU - Gazi, Peter
AU - Pietrzak, Krzysztof Z
AU - Tessaro, Stefano
ID - 1671
TI - The exact PRF security of truncation: Tight bounds for keyed sponges and truncated CBC
VL - 9215
ER -
TY - JOUR
AB - When a new mutant arises in a population, there is a probability it outcompetes the residents and fixes. The structure of the population can affect this fixation probability. Suppressing population structures reduce the difference between two competing variants, while amplifying population structures enhance the difference. Suppressors are ubiquitous and easy to construct, but amplifiers for the large population limit are more elusive and only a few examples have been discovered. Whether or not a population structure is an amplifier of selection depends on the probability distribution for the placement of the invading mutant. First, we prove that there exist only bounded amplifiers for adversarial placement-that is, for arbitrary initial conditions. Next, we show that the Star population structure, which is known to amplify for mutants placed uniformly at random, does not amplify for mutants that arise through reproduction and are therefore placed proportional to the temperatures of the vertices. Finally, we construct population structures that amplify for all mutational events that arise through reproduction, uniformly at random, or through some combination of the two.
AU - Adlam, Ben
AU - Chatterjee, Krishnendu
AU - Nowak, Martin
ID - 1673
IS - 2181
JF - Proceedings of the Royal Society A: Mathematical, Physical and Engineering Sciences
TI - Amplifiers of selection
VL - 471
ER -
TY - CONF
AB - We revisit the security (as a pseudorandom permutation) of cascading-based constructions for block-cipher key-length extension. Previous works typically considered the extreme case where the adversary is given the entire codebook of the construction, the only complexity measure being the number qe of queries to the underlying ideal block cipher, representing adversary’s secret-key-independent computation. Here, we initiate a systematic study of the more natural case of an adversary restricted to adaptively learning a number qc of plaintext/ciphertext pairs that is less than the entire codebook. For any such qc, we aim to determine the highest number of block-cipher queries qe the adversary can issue without being able to successfully distinguish the construction (under a secret key) from a random permutation.
More concretely, we show the following results for key-length extension schemes using a block cipher with n-bit blocks and κ-bit keys:
Plain cascades of length ℓ=2r+1 are secure whenever qcqre≪2r(κ+n), qc≪2κ and qe≪22κ. The bound for r=1 also applies to two-key triple encryption (as used within Triple DES).
The r-round XOR-cascade is secure as long as qcqre≪2r(κ+n), matching an attack by Gaži (CRYPTO 2013).
We fully characterize the security of Gaži and Tessaro’s two-call
AU - Gazi, Peter
AU - Lee, Jooyoung
AU - Seurin, Yannick
AU - Steinberger, John
AU - Tessaro, Stefano
ID - 1668
TI - Relaxing full-codebook security: A refined analysis of key-length extension schemes
VL - 9054
ER -
TY - CONF
AB - Planning in hybrid domains poses a special challenge due to the involved mixed discrete-continuous dynamics. A recent solving approach for such domains is based on applying model checking techniques on a translation of PDDL+ planning problems to hybrid automata. However, the proposed translation is limited because must behavior is only overapproximated, and hence, processes and events are not reflected exactly. In this paper, we present the theoretical foundation of an exact PDDL+ translation. We propose a schema to convert a hybrid automaton with must transitions into an equivalent hybrid automaton featuring only may transitions.
AU - Bogomolov, Sergiy
AU - Magazzeni, Daniele
AU - Minopoli, Stefano
AU - Wehrle, Martin
ID - 1670
TI - PDDL+ planning with hybrid automata: Foundations of translating must behavior
ER -
TY - JOUR
AB - We consider N × N random matrices of the form H = W + V where W is a real symmetric Wigner matrix and V a random or deterministic, real, diagonal matrix whose entries are independent of W. We assume subexponential decay for the matrix entries of W and we choose V so that the eigenvalues of W and V are typically of the same order. For a large class of diagonal matrices V, we show that the rescaled distribution of the extremal eigenvalues is given by the Tracy-Widom distribution F1 in the limit of large N. Our proofs also apply to the complex Hermitian setting, i.e. when W is a complex Hermitian Wigner matrix.
AU - Lee, Jioon
AU - Schnelli, Kevin
ID - 1674
IS - 8
JF - Reviews in Mathematical Physics
TI - Edge universality for deformed Wigner matrices
VL - 27
ER -
TY - JOUR
AU - Lemoult, Grégoire M
AU - Maier, Philipp
AU - Hof, Björn
ID - 1679
IS - 9
JF - Physics of Fluids
TI - Taylor's Forest
VL - 27
ER -
TY - JOUR
AU - Sixt, Michael K
AU - Raz, Erez
ID - 1676
IS - 10
JF - Current Opinion in Cell Biology
TI - Editorial overview: Cell adhesion and migration
VL - 36
ER -
TY - JOUR
AB - Guided cell movement is essential for development and integrity of animals and crucially involved in cellular immune responses. Leukocytes are professional migratory cells that can navigate through most types of tissues and sense a wide range of directional cues. The responses of these cells to attractants have been mainly explored in tissue culture settings. How leukocytes make directional decisions in situ, within the challenging environment of a tissue maze, is less understood. Here we review recent advances in how leukocytes sense chemical cues in complex tissue settings and make links with paradigms of directed migration in development and Dictyostelium discoideum amoebae.
AU - Sarris, Milka
AU - Sixt, Michael K
ID - 1687
IS - 10
JF - Current Opinion in Cell Biology
TI - Navigating in tissue mazes: Chemoattractant interpretation in complex environments
VL - 36
ER -
TY - CONF
AB - Given a graph G cellularly embedded on a surface Σ of genus g, a cut graph is a subgraph of G such that cutting Σ along G yields a topological disk. We provide a fixed parameter tractable approximation scheme for the problem of computing the shortest cut graph, that is, for any ε > 0, we show how to compute a (1 + ε) approximation of the shortest cut graph in time f(ε, g)n3.
Our techniques first rely on the computation of a spanner for the problem using the technique of brick decompositions, to reduce the problem to the case of bounded tree-width. Then, to solve the bounded tree-width case, we introduce a variant of the surface-cut decomposition of Rué, Sau and Thilikos, which may be of independent interest.
AU - Cohen Addad, Vincent
AU - De Mesmay, Arnaud N
ID - 1685
TI - A fixed parameter tractable approximation scheme for the optimal cut graph of a surface
VL - 9294
ER -
TY - JOUR
AB - We estimate the selection constant in the following geometric selection theorem by Pach: For every positive integer d, there is a constant (Formula presented.) such that whenever (Formula presented.) are n-element subsets of (Formula presented.), we can find a point (Formula presented.) and subsets (Formula presented.) for every i∈[d+1], each of size at least cdn, such that p belongs to all rainbowd-simplices determined by (Formula presented.) simplices with one vertex in each Yi. We show a super-exponentially decreasing upper bound (Formula presented.). The ideas used in the proof of the upper bound also help us to prove Pach’s theorem with (Formula presented.), which is a lower bound doubly exponentially decreasing in d (up to some polynomial in the exponent). For comparison, Pach’s original approach yields a triply exponentially decreasing lower bound. On the other hand, Fox, Pach, and Suk recently obtained a hypergraph density result implying a proof of Pach’s theorem with (Formula presented.). In our construction for the upper bound, we use the fact that the minimum solid angle of every d-simplex is super-exponentially small. This fact was previously unknown and might be of independent interest. For the lower bound, we improve the ‘separation’ part of the argument by showing that in one of the key steps only d+1 separations are necessary, compared to 2d separations in the original proof. We also provide a measure version of Pach’s theorem.
AU - Karasev, Roman
AU - Kynčl, Jan
AU - Paták, Pavel
AU - Patakova, Zuzana
AU - Tancer, Martin
ID - 1688
IS - 3
JF - Discrete & Computational Geometry
TI - Bounds for Pach's selection theorem and for the minimum solid angle in a simplex
VL - 54
ER -
TY - JOUR
AB - We consider the satisfiability problem for modal logic over first-order definable classes of frames.We confirm the conjecture from Hemaspaandra and Schnoor [2008] that modal logic is decidable over classes definable by universal Horn formulae. We provide a full classification of Horn formulae with respect to the complexity of the corresponding satisfiability problem. It turns out, that except for the trivial case of inconsistent formulae, local satisfiability is eitherNP-complete or PSPACE-complete, and global satisfiability is NP-complete, PSPACE-complete, or ExpTime-complete. We also show that the finite satisfiability problem for modal logic over Horn definable classes of frames is decidable. On the negative side, we show undecidability of two related problems. First, we exhibit a simple universal three-variable formula defining the class of frames over which modal logic is undecidable. Second, we consider the satisfiability problem of bimodal logic over Horn definable classes of frames, and also present a formula leading to undecidability.
AU - Michaliszyn, Jakub
AU - Otop, Jan
AU - Kieroňski, Emanuel
ID - 1680
IS - 1
JF - ACM Transactions on Computational Logic
TI - On the decidability of elementary modal logics
VL - 17
ER -
TY - JOUR
AB - We study the problem of robust satisfiability of systems of nonlinear equations, namely, whether for a given continuous function f:K→ ℝn on a finite simplicial complex K and α > 0, it holds that each function g: K → ℝn such that ||g - f || ∞ < α, has a root in K. Via a reduction to the extension problem of maps into a sphere, we particularly show that this problem is decidable in polynomial time for every fixed n, assuming dimK ≤ 2n - 3. This is a substantial extension of previous computational applications of topological degree and related concepts in numerical and interval analysis. Via a reverse reduction, we prove that the problem is undecidable when dim K > 2n - 2, where the threshold comes from the stable range in homotopy theory. For the lucidity of our exposition, we focus on the setting when f is simplexwise linear. Such functions can approximate general continuous functions, and thus we get approximation schemes and undecidability of the robust satisfiability in other possible settings.
AU - Franek, Peter
AU - Krcál, Marek
ID - 1682
IS - 4
JF - Journal of the ACM
TI - Robust satisfiability of systems of equations
VL - 62
ER -
TY - JOUR
AB - The 1 MDa, 45-subunit proton-pumping NADH-ubiquinone oxidoreductase (complex I) is the largest complex of the mitochondrial electron transport chain. The molecular mechanism of complex I is central to the metabolism of cells, but has yet to be fully characterized. The last two years have seen steady progress towards this goal with the first atomic-resolution structure of the entire bacterial complex I, a 5 Å cryo-electron microscopy map of bovine mitochondrial complex I and a ∼3.8 Å resolution X-ray crystallographic study of mitochondrial complex I from yeast Yarrowia lipotytica. In this review we will discuss what we have learned from these studies and what remains to be elucidated.
AU - Letts, Jame A
AU - Sazanov, Leonid A
ID - 1683
IS - 8
JF - Current Opinion in Structural Biology
TI - Gaining mass: The structure of respiratory complex I-from bacterial towards mitochondrial versions
VL - 33
ER -
TY - JOUR
AU - Kiermaier, Eva
AU - Sixt, Michael K
ID - 1686
IS - 6252
JF - Science
TI - Fragmented communication between immune cells: Neutrophils blaze a trail with migratory cues for T cells to follow to sites of infection
VL - 349
ER -
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 - CONF
AB - A number of powerful and scalable hybrid systems model checkers have recently emerged. Although all of them honor roughly the same hybrid systems semantics, they have drastically different model description languages. This situation (a) makes it difficult to quickly evaluate a specific hybrid automaton model using the different tools, (b) obstructs comparisons of reachability approaches, and (c) impedes the widespread application of research results that perform model modification and could benefit many of the tools. In this paper, we present Hyst, a Hybrid Source Transformer. Hyst is a source-to-source translation tool, currently taking input in the SpaceEx model format, and translating to the formats of HyCreate, Flow∗, or dReach. Internally, the tool supports generic model-to-model transformation passes that serve to both ease the translation and potentially improve reachability results for the supported tools. Although these model transformation passes could be implemented within each tool, the Hyst approach provides a single place for model modification, generating modified input sources for the unmodified target tools. Our evaluation demonstrates Hyst is capable of automatically translating benchmarks in several classes (including affine and nonlinear hybrid automata) to the input formats of several tools. Additionally, we illustrate a general model transformation pass based on pseudo-invariants implemented in Hyst that illustrates the reachability improvement.
AU - Bak, Stanley
AU - Bogomolov, Sergiy
AU - Johnson, Taylor
ID - 1690
TI - HYST: A source transformation and translation tool for hybrid automaton models
ER -
TY - CONF
AB - We consider a case study of the problem of deploying an autonomous air vehicle in a partially observable, dynamic, indoor environment from a specification given as a linear temporal logic (LTL) formula over regions of interest. We model the motion and sensing capabilities of the vehicle as a partially observable Markov decision process (POMDP). We adapt recent results for solving POMDPs with parity objectives to generate a control policy. We also extend the existing framework with a policy minimization technique to obtain a better implementable policy, while preserving its correctness. The proposed techniques are illustrated in an experimental setup involving an autonomous quadrotor performing surveillance in a dynamic environment.
AU - Svoreňová, Mária
AU - Chmelik, Martin
AU - Leahy, Kevin
AU - Eniser, Hasan
AU - Chatterjee, Krishnendu
AU - Cěrná, Ivana
AU - Belta, Cǎlin
ID - 1691
T2 - Proceedings of the 18th International Conference on Hybrid Systems: Computation and Control
TI - Temporal logic motion planning using POMDPs with parity objectives: Case study paper
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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 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 - 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 - 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 - 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 - 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 - 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 - 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 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
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 - 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 - 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 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
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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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
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
AU - Jonas, Peter M
ID - 1845
IS - 6
JF - Neuron
TI - Excitement about inhibitory presynaptic terminals
VL - 85
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
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
AU - Grones, Peter
AU - Friml, Jiřĺ
ID - 1847
IS - 3
JF - Molecular Plant
TI - ABP1: Finally docking
VL - 8
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
SN - 0014-3820
TI - Evolutionarily stable mating decisions for sequentially searching females and the stability of reproductive isolation by assortative mating
VL - 69
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 - 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 - 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 - 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 - 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
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 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 - 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
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 - 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 - 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 - 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 - 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 - 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 - 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 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
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 - Rakusová, Hana
AU - Fendrych, Matyas
AU - Friml, Jirí
ID - 1944
IS - 2
JF - Current Opinion in Plant Biology
TI - Intracellular trafficking and PIN-mediated cell polarity during tropic responses in plants
VL - 23
ER -
TY - CONF
AB - We present a method and a tool for generating succinct representations of sets of concurrent traces. We focus on trace sets that contain all correct or all incorrect permutations of events from a given trace. We represent trace sets as HB-Formulas that are Boolean combinations of happens-before constraints between events. To generate a representation of incorrect interleavings, our method iteratively explores interleavings that violate the specification and gathers generalizations of the discovered interleavings into an HB-Formula; its complement yields a representation of correct interleavings.
We claim that our trace set representations can drive diverse verification, fault localization, repair, and synthesis techniques for concurrent programs. We demonstrate this by using our tool in three case studies involving synchronization synthesis, bug summarization, and abstraction refinement based verification. In each case study, our initial experimental results have been promising.
In the first case study, we present an algorithm for inferring missing synchronization from an HB-Formula representing correct interleavings of a given trace. The algorithm applies rules to rewrite specific patterns in the HB-Formula into locks, barriers, and wait-notify constructs. In the second case study, we use an HB-Formula representing incorrect interleavings for bug summarization. While the HB-Formula itself is a concise counterexample summary, we present additional inference rules to help identify specific concurrency bugs such as data races, define-use order violations, and two-stage access bugs. In the final case study, we present a novel predicate learning procedure that uses HB-Formulas representing abstract counterexamples to accelerate counterexample-guided abstraction refinement (CEGAR). In each iteration of the CEGAR loop, the procedure refines the abstraction to eliminate multiple spurious abstract counterexamples drawn from the HB-Formula.
AU - Gupta, Ashutosh
AU - Henzinger, Thomas A
AU - Radhakrishna, Arjun
AU - Samanta, Roopsha
AU - Tarrach, Thorsten
ID - 1992
SN - 978-1-4503-3300-9
TI - Succinct representation of concurrent trace sets
ER -
TY - JOUR
AB - We prove that the three-state toric homogeneous Markov chain model has Markov degree two. In algebraic terminology this means, that a certain class of toric ideals is generated by quadratic binomials. This was conjectured by Haws, Martin del Campo, Takemura and Yoshida, who proved that they are generated by degree six binomials.
AU - Noren, Patrik
ID - 1997
IS - May-June
JF - Journal of Symbolic Computation
TI - The three-state toric homogeneous Markov chain model has Markov degree two
VL - 68/Part 2
ER -
TY - JOUR
AB - The paper describes a generalized iterative proportional fitting procedure that can be used for maximum likelihood estimation in a special class of the general log-linear model. The models in this class, called relational, apply to multivariate discrete sample spaces that do not necessarily have a Cartesian product structure and may not contain an overall effect. When applied to the cell probabilities, the models without the overall effect are curved exponential families and the values of the sufficient statistics are reproduced by the MLE only up to a constant of proportionality. The paper shows that Iterative Proportional Fitting, Generalized Iterative Scaling, and Improved Iterative Scaling fail to work for such models. The algorithm proposed here is based on iterated Bregman projections. As a by-product, estimates of the multiplicative parameters are also obtained. An implementation of the algorithm is available as an R-package.
AU - Klimova, Anna
AU - Rudas, Tamás
ID - 2008
IS - 3
JF - Scandinavian Journal of Statistics
TI - Iterative scaling in curved exponential families
VL - 42
ER -
TY - JOUR
AB - The monotone secant conjecture posits a rich class of polynomial systems, all of whose solutions are real. These systems come from the Schubert calculus on flag manifolds, and the monotone secant conjecture is a compelling generalization of the Shapiro conjecture for Grassmannians (Theorem of Mukhin, Tarasov, and Varchenko). We present some theoretical evidence for this conjecture, as well as computational evidence obtained by 1.9 teraHertz-years of computing, and we discuss some of the phenomena we observed in our data.
AU - Hein, Nicolas
AU - Hillar, Christopher
AU - Martin Del Campo Sanchez, Abraham
AU - Sottile, Frank
AU - Teitler, Zach
ID - 2006
IS - 3
JF - Experimental Mathematics
TI - The monotone secant conjecture in the real Schubert calculus
VL - 24
ER -
TY - JOUR
AB - The concepts of faithfulness and strong-faithfulness are important for statistical learning of graphical models. Graphs are not sufficient for describing the association structure of a discrete distribution. Hypergraphs representing hierarchical log-linear models are considered instead, and the concept of parametric (strong-) faithfulness with respect to a hypergraph is introduced. Strong-faithfulness ensures the existence of uniformly consistent parameter estimators and enables building uniformly consistent procedures for a hypergraph search. The strength of association in a discrete distribution can be quantified with various measures, leading to different concepts of strong-faithfulness. Lower and upper bounds for the proportions of distributions that do not satisfy strong-faithfulness are computed for different parameterizations and measures of association.
AU - Klimova, Anna
AU - Uhler, Caroline
AU - Rudas, Tamás
ID - 2014
IS - 7
JF - Computational Statistics & Data Analysis
TI - Faithfulness and learning hypergraphs from discrete distributions
VL - 87
ER -
TY - JOUR
AB - Small GTP-binding proteins of the Ras superfamily play diverse roles in intracellular trafficking. Among them, the Rab, Arf, and Rho families function in successive steps of vesicle transport, in forming vesicles from donor membranes, directing vesicle trafficking toward target membranes and docking vesicles onto target membranes. These proteins act as molecular switches that are controlled by a cycle of GTP binding and hydrolysis regulated by guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs). In this study we explored the role of GAPs in the regulation of the endocytic pathway using fluorescently labeled yeast mating pheromone α-factor. Among 25 non-essential GAP mutants, we found that deletion of the GLO3 gene, encoding Arf-GAP protein, caused defective internalization of fluorescently labeled α-factor. Quantitative analysis revealed that glo3Δ cells show defective α-factor binding to the cell surface. Interestingly, Ste2p, the α-factor receptor, was mis-localized from the plasma membrane to the vacuole in glo3Δ cells. Domain deletion mutants of Glo3p revealed that a GAP-independent function, as well as the GAP activity, of Glo3p is important for both α-factor binding and Ste2p localization at the cell surface. Additionally, we found that deletion of the GLO3 gene affects the size and number of Arf1p-residing Golgi compartments and causes a defect in transport from the TGN to the plasma membrane. Furthermore, we demonstrated that glo3Δ cells were defective in the late endosome-to-TGN transport pathway, but not in the early endosome-to-TGN transport pathway. These findings suggest novel roles for Arf-GAP Glo3p in endocytic recycling of cell surface proteins.
AU - Kawada, Daiki
AU - Kobayashi, Hiromu
AU - Tomita, Tsuyoshi
AU - Nakata, Eisuke
AU - Nagano, Makoto
AU - Siekhaus, Daria E
AU - Toshima, Junko
AU - Toshimaa, Jiro
ID - 2025
IS - 1
JF - Biochimica et Biophysica Acta - Molecular Cell Research
TI - The yeast Arf-GAP Glo3p is required for the endocytic recycling of cell surface proteins
VL - 1853
ER -
TY - JOUR
AB - A hybrid-parallel direct-numerical-simulation method with application to turbulent Taylor-Couette flow is presented. The Navier-Stokes equations are discretized in cylindrical coordinates with the spectral Fourier-Galerkin method in the axial and azimuthal directions, and high-order finite differences in the radial direction. Time is advanced by a second-order, semi-implicit projection scheme, which requires the solution of five Helmholtz/Poisson equations, avoids staggered grids and renders very small slip velocities. Nonlinear terms are evaluated with the pseudospectral method. The code is parallelized using a hybrid MPI-OpenMP strategy, which, compared with a flat MPI parallelization, is simpler to implement, allows to reduce inter-node communications and MPI overhead that become relevant at high processor-core counts, and helps to contain the memory footprint. A strong scaling study shows that the hybrid code maintains scalability up to more than 20,000 processor cores and thus allows to perform simulations at higher resolutions than previously feasible. In particular, it opens up the possibility to simulate turbulent Taylor-Couette flows at Reynolds numbers up to O(105). This enables to probe hydrodynamic turbulence in Keplerian flows in experimentally relevant regimes.
AU - Shi, Liang
AU - Rampp, Markus
AU - Hof, Björn
AU - Avila, Marc
ID - 2030
IS - 1
JF - Computers and Fluids
TI - A hybrid MPI-OpenMP parallel implementation for pseudospectral simulations with application to Taylor-Couette flow
VL - 106
ER -