TY - JOUR
AB - Gene expression is controlled by networks of regulatory proteins that interact specifically with external signals and DNA regulatory sequences. These interactions force the network components to co-evolve so as to continually maintain function. Yet, existing models of evolution mostly focus on isolated genetic elements. In contrast, we study the essential process by which regulatory networks grow: the duplication and subsequent specialization of network components. We synthesize a biophysical model of molecular interactions with the evolutionary framework to find the conditions and pathways by which new regulatory functions emerge. We show that specialization of new network components is usually slow, but can be drastically accelerated in the presence of regulatory crosstalk and mutations that promote promiscuous interactions between network components.
AU - Friedlander, Tamar
AU - Prizak, Roshan
AU - Barton, Nicholas H
AU - Tkacik, Gasper
ID - 955
IS - 1
JF - Nature Communications
SN - 20411723
TI - Evolution of new regulatory functions on biophysically realistic fitness landscapes
VL - 8
ER -
TY - JOUR
AB - We study a class of ergodic quantum Markov semigroups on finite-dimensional unital C⁎-algebras. These semigroups have a unique stationary state σ, and we are concerned with those that satisfy a quantum detailed balance condition with respect to σ. We show that the evolution on the set of states that is given by such a quantum Markov semigroup is gradient flow for the relative entropy with respect to σ in a particular Riemannian metric on the set of states. This metric is a non-commutative analog of the 2-Wasserstein metric, and in several interesting cases we are able to show, in analogy with work of Otto on gradient flows with respect to the classical 2-Wasserstein metric, that the relative entropy is strictly and uniformly convex with respect to the Riemannian metric introduced here. As a consequence, we obtain a number of new inequalities for the decay of relative entropy for ergodic quantum Markov semigroups with detailed balance.
AU - Carlen, Eric
AU - Maas, Jan
ID - 956
IS - 5
JF - Journal of Functional Analysis
SN - 00221236
TI - Gradient flow and entropy inequalities for quantum Markov semigroups with detailed balance
VL - 273
ER -
TY - JOUR
AB - In this work it is shown that scale-free tails in metabolic flux distributions inferred in stationary models are an artifact due to reactions involved in thermodynamically unfeasible cycles, unbounded by physical constraints and in principle able to perform work without expenditure of free energy. After implementing thermodynamic constraints by removing such loops, metabolic flux distributions scale meaningfully with the physical limiting factors, acquiring in turn a richer multimodal structure potentially leading to symmetry breaking while optimizing for objective functions.
AU - De Martino, Daniele
ID - 959
IS - 6
JF - Physical Review E Statistical Nonlinear and Soft Matter Physics
SN - 24700045
TI - Scales and multimodal flux distributions in stationary metabolic network models via thermodynamics
VL - 95
ER -
TY - JOUR
AB - The human cerebral cortex is the seat of our cognitive abilities and composed of an extraordinary number of neurons, organized in six distinct layers. The establishment of specific morphological and physiological features in individual neurons needs to be regulated with high precision. Impairments in the sequential developmental programs instructing corticogenesis lead to alterations in the cortical cytoarchitecture which is thought to represent the major underlying cause for several neurological disorders including neurodevelopmental and psychiatric diseases. In this review we discuss the role of cell polarity at sequential stages during cortex development. We first provide an overview of morphological cell polarity features in cortical neural stem cells and newly-born postmitotic neurons. We then synthesize a conceptual molecular and biochemical framework how cell polarity is established at the cellular level through a break in symmetry in nascent cortical projection neurons. Lastly we provide a perspective how the molecular mechanisms applying to single cells could be probed and integrated in an in vivo and tissue-wide context.
AU - Hansen, Andi H
AU - Düllberg, Christian F
AU - Mieck, Christine
AU - Loose, Martin
AU - Hippenmeyer, Simon
ID - 960
JF - Frontiers in Cellular Neuroscience
SN - 16625102
TI - Cell polarity in cerebral cortex development - cellular architecture shaped by biochemical networks
VL - 11
ER -
TY - THES
AB - Cell-cell contact formation constitutes the first step in the emergence of multicellularity in evolution, thereby allowing the differentiation of specialized cell types. In metazoan development, cell-cell contact formation is thought to influence cell fate specification, and cell fate specification has been implicated in cell-cell contact formation. However, remarkably little is yet known about whether and how the interaction and feedback between cell-cell contact formation and cell fate specification affect development. Here we identify a positive feedback loop between cell-cell contact duration, morphogen signaling and mesendoderm cell fate specification during zebrafish gastrulation. We show that long lasting cell-cell contacts enhance the competence of prechordal plate (ppl) progenitor cells to respond to Nodal signaling, required for proper ppl cell fate specification. We further show that Nodal signalling romotes ppl cell-cell contact duration, thereby generating an effective positive feedback loop between ppl cell-cell contact duration and cell fate specification. Finally, by using a combination of theoretical modeling and experimentation, we show that this feedback loop determines whether anterior axial mesendoderm cells become ppl progenitors or, instead, turn into endoderm progenitors. Our findings reveal that the gene regulatory networks leading to cell fate diversification within the developing embryo are controlled by the interdependent activities of cell-cell signaling and contact formation.
AU - Barone, Vanessa
ID - 961
TI - Cell adhesion and cell fate: An effective feedback loop during zebrafish gastrulation
ER -
TY - CONF
AB - Network games are widely used as a model for selfish resource-allocation problems. In the classical model, each player selects a path connecting her source and target vertex. The cost of traversing an edge depends on the number of players that traverse it. Thus, it abstracts the fact that different users may use a resource at different times and for different durations, which plays an important role in defining the costs of the users in reality. For example, when transmitting packets in a communication network, routing traffic in a road network, or processing a task in a production system, the traversal of the network involves an inherent delay, and so sharing and congestion of resources crucially depends on time. We study timed network games , which add a time component to network games. Each vertex v in the network is associated with a cost function, mapping the load on v to the price that a player pays for staying in v for one time unit with this load. In addition, each edge has a guard, describing time intervals in which the edge can be traversed, forcing the players to spend time on vertices. Unlike earlier work that add a time component to network games, the time in our model is continuous and cannot be discretized. In particular, players have uncountably many strategies, and a game may have uncountably many pure Nash equilibria. We study properties of timed network games with cost-sharing or congestion cost functions: their stability, equilibrium inefficiency, and complexity. In particular, we show that the answer to the question whether we can restrict attention to boundary strategies, namely ones in which edges are traversed only at the boundaries of guards, is mixed.
AU - Avni, Guy
AU - Guha, Shibashis
AU - Kupferman, Orna
ID - 963
SN - 18688969
TI - Timed network games with clocks
VL - 83
ER -
TY - JOUR
AB - The current-phase relation (CPR) of a Josephson junction (JJ) determines how the supercurrent evolves with the superconducting phase difference across the junction. Knowledge of the CPR is essential in order to understand the response of a JJ to various external parameters. Despite the rising interest in ultraclean encapsulated graphene JJs, the CPR of such junctions remains unknown. Here, we use a fully gate-tunable graphene superconducting quantum intereference device (SQUID) to determine the CPR of ballistic graphene JJs. Each of the two JJs in the SQUID is made with graphene encapsulated in hexagonal boron nitride. By independently controlling the critical current of the JJs, we can operate the SQUID either in a symmetric or asymmetric configuration. The highly asymmetric SQUID allows us to phase-bias one of the JJs and thereby directly obtain its CPR. The CPR is found to be skewed, deviating significantly from a sinusoidal form. The skewness can be tuned with the gate voltage and oscillates in antiphase with Fabry-Pérot resistance oscillations of the ballistic graphene cavity. We compare our experiments with tight-binding calculations that include realistic graphene-superconductor interfaces and find a good qualitative agreement.
AU - Nanda, Gaurav
AU - Aguilera Servin, Juan L
AU - Rakyta, Péter
AU - Kormányos, Andor
AU - Kleiner, Reinhold
AU - Koelle, Dieter
AU - Watanabe, Kazuo
AU - Taniguchi, Takashi
AU - Vandersypen, Lieven
AU - Goswami, Srijit
ID - 988
IS - 6
JF - Nano Letters
SN - 15306984
TI - Current-phase relation of ballistic graphene Josephson junctions
VL - 17
ER -
TY - JOUR
AB - Assortative mating is an important driver of speciation in populations with gene flow and is predicted to evolve under certain conditions in few-locus models. However, the evolution of assortment is less understood for mating based on quantitative traits, which are often characterized by high genetic variability and extensive linkage disequilibrium between trait loci. We explore this scenario for a two-deme model with migration, by considering a single polygenic trait subject to divergent viability selection across demes, as well as assortative mating and sexual selection within demes, and investigate how trait divergence is shaped by various evolutionary forces. Our analysis reveals the existence of sharp thresholds of assortment strength, at which divergence increases dramatically. We also study the evolution of assortment via invasion of modifiers of mate discrimination and show that the ES assortment strength has an intermediate value under a range of migration-selection parameters, even in diverged populations, due to subtle effects which depend sensitively on the extent of phenotypic variation within these populations. The evolutionary dynamics of the polygenic trait is studied using the hypergeometric and infinitesimal models. We further investigate the sensitivity of our results to the assumptions of the hypergeometric model, using individual-based simulations.
AU - Sachdeva, Himani
AU - Barton, Nicholas H
ID - 990
IS - 6
JF - Evolution; International Journal of Organic Evolution
SN - 00143820
TI - Divergence and evolution of assortative mating in a polygenic trait model of speciation with gene flow
VL - 71
ER -
TY - THES
AB - An instance of the Constraint Satisfaction Problem (CSP) is given by a finite set of
variables, a finite domain of labels, and a set of constraints, each constraint acting on
a subset of the variables. The goal is to find an assignment of labels to its variables
that satisfies all constraints (or decide whether one exists). If we allow more general
“soft” constraints, which come with (possibly infinite) costs of particular assignments,
we obtain instances from a richer class called Valued Constraint Satisfaction Problem
(VCSP). There the goal is to find an assignment with minimum total cost.
In this thesis, we focus (assuming that P
6
=
NP) on classifying computational com-
plexity of CSPs and VCSPs under certain restricting conditions. Two results are the core
content of the work. In one of them, we consider VCSPs parametrized by a constraint
language, that is the set of “soft” constraints allowed to form the instances, and finish
the complexity classification modulo (missing pieces of) complexity classification for
analogously parametrized CSP. The other result is a generalization of Edmonds’ perfect
matching algorithm. This generalization contributes to complexity classfications in two
ways. First, it gives a new (largest known) polynomial-time solvable class of Boolean
CSPs in which every variable may appear in at most two constraints and second, it
settles full classification of Boolean CSPs with planar drawing (again parametrized by a
constraint language).
AU - Rolinek, Michal
ID - 992
TI - Complexity of constraint satisfaction
ER -
TY - JOUR
AB - In real-world applications, observations are often constrained to a small fraction of a system. Such spatial subsampling can be caused by the inaccessibility or the sheer size of the system, and cannot be overcome by longer sampling. Spatial subsampling can strongly bias inferences about a system’s aggregated properties. To overcome the bias, we derive analytically a subsampling scaling framework that is applicable to different observables, including distributions of neuronal avalanches, of number of people infected during an epidemic outbreak, and of node degrees. We demonstrate how to infer the correct distributions of the underlying full system, how to apply it to distinguish critical from subcritical systems, and how to disentangle subsampling and finite size effects. Lastly, we apply subsampling scaling to neuronal avalanche models and to recordings from developing neural networks. We show that only mature, but not young networks follow power-law scaling, indicating self-organization to criticality during development.
AU - Levina (Martius), Anna
AU - Priesemann, Viola
ID - 993
JF - Nature Communications
SN - 20411723
TI - Subsampling scaling
VL - 8
ER -
TY - JOUR
AB - The formation of vortices is usually considered to be the main mechanism of angular momentum disposal in superfluids. Recently, it was predicted that a superfluid can acquire angular momentum via an alternative, microscopic route -- namely, through interaction with rotating impurities, forming so-called `angulon quasiparticles' [Phys. Rev. Lett. 114, 203001 (2015)]. The angulon instabilities correspond to transfer of a small number of angular momentum quanta from the impurity to the superfluid, as opposed to vortex instabilities, where angular momentum is quantized in units of ℏ per atom. Furthermore, since conventional impurities (such as molecules) represent three-dimensional (3D) rotors, the angular momentum transferred is intrinsically 3D as well, as opposed to a merely planar rotation which is inherent to vortices. Herein we show that the angulon theory can explain the anomalous broadening of the spectroscopic lines observed for CH 3 and NH 3 molecules in superfluid helium nanodroplets, thereby providing a fingerprint of the emerging angulon instabilities in experiment.
AU - Cherepanov, Igor
AU - Lemeshko, Mikhail
ID - 994
IS - 3
JF - Physical Review Materials
TI - Fingerprints of angulon instabilities in the spectra of matrix-isolated molecules
VL - 1
ER -
TY - JOUR
AB - Recently it was shown that an impurity exchanging orbital angular momentum with a surrounding bath can be described in terms of the angulon quasiparticle [Phys. Rev. Lett. 118, 095301 (2017)]. The angulon consists of a quantum rotor dressed by a many-particle field of boson excitations, and can be formed out of, for example, a molecule or a nonspherical atom in superfluid helium, or out of an electron coupled to lattice phonons or a Bose condensate. Here we develop an approach to the angulon based on the path-integral formalism, which sets the ground for a systematic, perturbative treatment of the angulon problem. The resulting perturbation series can be interpreted in terms of Feynman diagrams, from which, in turn, one can derive a set of diagrammatic rules. These rules extend the machinery of the graphical theory of angular momentum - well known from theoretical atomic spectroscopy - to the case where an environment with an infinite number of degrees of freedom is present. In particular, we show that each diagram can be interpreted as a 'skeleton', which enforces angular momentum conservation, dressed by an additional many-body contribution. This connection between the angulon theory and the graphical theory of angular momentum is particularly important as it allows to systematically and substantially simplify the analytical representation of each diagram. In order to exemplify the technique, we calculate the 1- and 2-loop contributions to the angulon self-energy, the spectral function, and the quasiparticle weight. The diagrammatic theory we develop paves the way to investigate next-to-leading order quantities in a more compact way compared to the variational approaches.
AU - Bighin, Giacomo
AU - Lemeshko, Mikhail
ID - 995
IS - 8
JF - Physical Review B - Condensed Matter and Materials Physics
SN - 24699950
TI - Diagrammatic approach to orbital quantum impurities interacting with a many-particle environment
VL - 96
ER -
TY - JOUR
AB - Iodine (I 2 ) molecules embedded in He nanodroplets are aligned by a 160 ps long laser pulse. The highest degree of alignment, occurring at the peak of the pulse and quantified by ⟨cos 2 θ 2D ⟩ , is measured as a function of the laser intensity. The results are well described by ⟨cos 2 θ 2D ⟩ calculated for a gas of isolated molecules each with an effective rotational constant of 0.6 times the gas-phase value, and at a temperature of 0.4 K. Theoretical analysis using the angulon quasiparticle to describe rotating molecules in superfluid helium rationalizes why the alignment mechanism is similar to that of isolated molecules with an effective rotational constant. A major advantage of molecules in He droplets is that their 0.4 K temperature leads to stronger alignment than what can generally be achieved for gas phase molecules -- here demonstrated by a direct comparison of the droplet results to measurements on a ∼ 1 K supersonic beam of isolated molecules. This point is further illustrated for more complex system by measurements on 1,4-diiodobenzene and 1,4-dibromobenzene. For all three molecular species studied the highest values of ⟨cos 2 θ 2D ⟩ achieved in He droplets exceed 0.96.
AU - Shepperson, Benjamin
AU - Chatterley, Adam
AU - Søndergaard, Anders
AU - Christiansen, Lars
AU - Lemeshko, Mikhail
AU - Stapelfeldt, Henrik
ID - 996
IS - 1
JF - The Journal of Chemical Physics
SN - 00219606
TI - Strongly aligned molecules inside helium droplets in the near-adiabatic regime
VL - 147
ER -
TY - JOUR
AB - Recently it was shown that molecules rotating in superfluid helium can be described in terms of the angulon quasiparticles (Phys. Rev. Lett. 118, 095301 (2017)). Here we demonstrate that in the experimentally realized regime the angulon can be seen as a point charge on a 2-sphere interacting with a gauge field of a non-abelian magnetic monopole. Unlike in several other settings, the gauge fields of the angulon problem emerge in the real coordinate space, as opposed to the momentum space or some effective parameter space. Furthermore, we find a topological transition associated with making the monopole abelian, which takes place in the vicinity of the previously reported angulon instabilities. These results pave the way for studying topological phenomena in experiments on molecules trapped in superfluid helium nanodroplets, as well as on other realizations of orbital impurity problems.
AU - Yakaboylu, Enderalp
AU - Deuchert, Andreas
AU - Lemeshko, Mikhail
ID - 997
IS - 23
JF - APS Physics, Physical Review Letters
SN - 00319007
TI - Emergence of non-abelian magnetic monopoles in a quantum impurity problem
VL - 119
ER -
TY - CONF
AB - A major open problem on the road to artificial intelligence is the development of incrementally learning systems that learn about more and more concepts over time from a stream of data. In this work, we introduce a new training strategy, iCaRL, that allows learning in such a class-incremental way: only the training data for a small number of classes has to be present at the same time and new classes can be added progressively. iCaRL learns strong classifiers and a data representation simultaneously. This distinguishes it from earlier works that were fundamentally limited to fixed data representations and therefore incompatible with deep learning architectures. We show by experiments on CIFAR-100 and ImageNet ILSVRC 2012 data that iCaRL can learn many classes incrementally over a long period of time where other strategies quickly fail.
AU - Rebuffi, Sylvestre Alvise
AU - Kolesnikov, Alexander
AU - Sperl, Georg
AU - Lampert, Christoph
ID - 998
SN - 978-153860457-1
TI - iCaRL: Incremental classifier and representation learning
VL - 2017
ER -
TY - JOUR
AB - We used femtosecond optical pump-probe spectroscopy to study the photoinduced change in reflectivity of thin films of the electron-doped cuprate La2-xCexCuO4 (LCCO) with dopings of x=0.08 (underdoped) and x=0.11 (optimally doped). Above Tc, we observe fluence-dependent relaxation rates that begin at a temperature similar to the one where transport measurements first show signatures of antiferromagnetic correlations. Upon suppressing superconductivity with a magnetic field, it is found that the fluence and temperature dependence of relaxation rates are consistent with bimolecular recombination of electrons and holes across a gap (2ΔAF) originating from antiferromagnetic correlations which comprise the pseudogap in electron-doped cuprates. This can be used to learn about coupling between electrons and high-energy (ω>2ΔAF) excitations in these compounds and set limits on the time scales on which antiferromagnetic correlations are static.
AU - Vishik, Inna
AU - Mahmood, Fahad
AU - Alpichshev, Zhanybek
AU - Gedik, Nuh
AU - Higgins, Joshu
AU - Greene, Richard
ID - 392
IS - 11
JF - Physical Review B
TI - Ultrafast dynamics in the presence of antiferromagnetic correlations in electron doped cuprate La2 xCexCuO4±δ
VL - 95
ER -
TY - JOUR
AB - We use a three-pulse ultrafast optical spectroscopy to study the relaxation processes in a frustrated Mott insulator Na2IrO3. By being able to independently produce the out-of-equilibrium bound states (excitons) of doublons and holons with the first pulse and suppress the underlying antiferromagnetic order with the second one, we were able to elucidate the relaxation mechanism of quasiparticles in this system. By observing the difference in the exciton dynamics in the magnetically ordered and disordered phases we found that the mass of this quasiparticle is mostly determined by its interaction with the surrounding spins.
AU - Alpichshev, Zhanybek
AU - Sie, Edbert
AU - Mahmood, Fahad
AU - Cao, Gang
AU - Gedik, Nuh
ID - 393
IS - 23
JF - Physical Review B
TI - Origin of the exciton mass in the frustrated Mott insulator Na2IrO3
VL - 96
ER -
TY - CHAP
AB - We show that very weak topological assumptions are enough to ensure the existence of a Helly-type theorem. More precisely, we show that for any non-negative integers b and d there exists an integer h(b, d) such that the following holds. If F is a finite family of subsets of Rd such that βi(∩G)≤b for any G⊊F and every 0 ≤ i ≤ [d/2]-1 then F has Helly number at most h(b, d). Here βi denotes the reduced Z2-Betti numbers (with singular homology). These topological conditions are sharp: not controlling any of these [d/2] first Betti numbers allow for families with unbounded Helly number. Our proofs combine homological non-embeddability results with a Ramsey-based approach to build, given an arbitrary simplicial complex K, some well-behaved chain map C*(K)→C*(Rd).
AU - Goaoc, Xavier
AU - Paták, Pavel
AU - Patakova, Zuzana
AU - Tancer, Martin
AU - Wagner, Uli
ED - Loebl, Martin
ED - Nešetřil, Jaroslav
ED - Thomas, Robin
ID - 424
SN - 978-331944479-6
T2 - A Journey through Discrete Mathematics: A Tribute to Jiri Matousek
TI - Bounding helly numbers via betti numbers
ER -
TY - CONF
AB - Parallel implementations of stochastic gradient descent (SGD) have received significant research attention, thanks to its excellent scalability properties. A fundamental barrier when parallelizing SGD is the high bandwidth cost of communicating gradient updates between nodes; consequently, several lossy compresion heuristics have been proposed, by which nodes only communicate quantized gradients. Although effective in practice, these heuristics do not always converge. In this paper, we propose Quantized SGD (QSGD), a family of compression schemes with convergence guarantees and good practical performance. QSGD allows the user to smoothly trade off communication bandwidth and convergence time: nodes can adjust the number of bits sent per iteration, at the cost of possibly higher variance. We show that this trade-off is inherent, in the sense that improving it past some threshold would violate information-theoretic lower bounds. QSGD guarantees convergence for convex and non-convex objectives, under asynchrony, and can be extended to stochastic variance-reduced techniques. When applied to training deep neural networks for image classification and automated speech recognition, QSGD leads to significant reductions in end-to-end training time. For instance, on 16GPUs, we can train the ResNet-152 network to full accuracy on ImageNet 1.8 × faster than the full-precision variant.
AU - Alistarh, Dan-Adrian
AU - Grubic, Demjan
AU - Li, Jerry
AU - Tomioka, Ryota
AU - Vojnović, Milan
ID - 431
SN - 10495258
TI - QSGD: Communication-efficient SGD via gradient quantization and encoding
VL - 2017
ER -
TY - CONF
AB - Recently there has been significant interest in training machine-learning models at low precision: by reducing precision, one can reduce computation and communication by one order of magnitude. We examine training at reduced precision, both from a theoretical and practical perspective, and ask: is it possible to train models at end-to-end low precision with provable guarantees? Can this lead to consistent order-of-magnitude speedups? We mainly focus on linear models, and the answer is yes for linear models. We develop a simple framework called ZipML based on one simple but novel strategy called double sampling. Our ZipML framework is able to execute training at low precision with no bias, guaranteeing convergence, whereas naive quanti- zation would introduce significant bias. We val- idate our framework across a range of applica- tions, and show that it enables an FPGA proto- type that is up to 6.5 × faster than an implemen- tation using full 32-bit precision. We further de- velop a variance-optimal stochastic quantization strategy and show that it can make a significant difference in a variety of settings. When applied to linear models together with double sampling, we save up to another 1.7 × in data movement compared with uniform quantization. When training deep networks with quantized models, we achieve higher accuracy than the state-of-the- art XNOR-Net.
AU - Zhang, Hantian
AU - Li, Jerry
AU - Kara, Kaan
AU - Alistarh, Dan-Adrian
AU - Liu, Ji
AU - Zhang, Ce
ID - 432
SN - 978-151085514-4
T2 - Proceedings of Machine Learning Research
TI - ZipML: Training linear models with end-to-end low precision, and a little bit of deep learning
VL - 70
ER -
TY - JOUR
AB - Pancreatic cancer has a five-year survival rate of ~8%, with characteristic molecular heterogeneity and restricted treatment options. Targeting metabolism has emerged as a potentially effective therapeutic strategy for cancers such as pancreatic cancer, which are driven by genetic alterations that are not tractable drug targets. Although somatic mitochondrial genome (mtDNA) mutations have been observed in various tumors types, understanding of metabolic genotype-phenotype relationships is limited.
AU - Hardie, Rae
AU - Van Dam, Ellen
AU - Cowley, Mark
AU - Han, Ting
AU - Balaban, Seher
AU - Pajic, Marina
AU - Pinese, Mark
AU - Iconomou, Mary
AU - Shearer, Robert
AU - Mckenna, Jessie
AU - Miller, David
AU - Waddell, Nicola
AU - Pearson, John
AU - Grimmond, Sean
AU - Sazanov, Leonid A
AU - Biankin, Andrew
AU - Villas Boas, Silas
AU - Hoy, Andrew
AU - Turner, Nigel
AU - Saunders, Darren
ID - 443
IS - 2
JF - Cancer & Metabolism
TI - Mitochondrial mutations and metabolic adaptation in pancreatic cancer
VL - 5
ER -
TY - JOUR
AB - The Loschmidt echo, defined as the overlap between quantum wave function evolved with different Hamiltonians, quantifies the sensitivity of quantum dynamics to perturbations and is often used as a probe of quantum chaos. In this work we consider the behavior of the Loschmidt echo in the many-body localized phase, which is characterized by emergent local integrals of motion and provides a generic example of nonergodic dynamics. We demonstrate that the fluctuations of the Loschmidt echo decay as a power law in time in the many-body localized phase, in contrast to the exponential decay in few-body ergodic systems. We consider the spin-echo generalization of the Loschmidt echo and argue that the corresponding correlation function saturates to a finite value in localized systems. Slow, power-law decay of fluctuations of such spin-echo-type overlap is related to the operator spreading and is present only in the many-body localized phase, but not in a noninteracting Anderson insulator. While most of the previously considered probes of dephasing dynamics could be understood by approximating physical spin operators with local integrals of motion, the Loschmidt echo and its generalizations crucially depend on the full expansion of the physical operators via local integrals of motion operators, as well as operators which flip local integrals of motion. Hence these probes allow one to get insights into the relation between physical operators and local integrals of motion and access the operator spreading in the many-body localized phase.
AU - Maksym Serbyn
AU - Abanin, Dimitry A
ID - 445
IS - 1
JF - Physical Review B - Condensed Matter and Materials Physics
TI - Loschmidt echo in many body localized phases
VL - 96
ER -
TY - JOUR
AB - We consider last passage percolation (LPP) models with exponentially distributed random variables, which are linked to the totally asymmetric simple exclusion process (TASEP). The competition interface for LPP was introduced and studied in Ferrari and Pimentel (2005a) for cases where the corresponding exclusion process had a rarefaction fan. Here we consider situations with a shock and determine the law of the fluctuations of the competition interface around its deter- ministic law of large number position. We also study the multipoint distribution of the LPP around the shock, extending our one-point result of Ferrari and Nejjar (2015).
AU - Ferrari, Patrik
AU - Nejjar, Peter
ID - 447
JF - Revista Latino-Americana de Probabilidade e Estatística
TI - Fluctuations of the competition interface in presence of shocks
VL - 9
ER -
TY - JOUR
AB - Most kinesin motors move in only one direction along microtubules. Members of the kinesin-5 subfamily were initially described as unidirectional plus-end-directed motors and shown to produce piconewton forces. However, some fungal kinesin-5 motors are bidirectional. The force production of a bidirectional kinesin-5 has not yet been measured. Therefore, it remains unknown whether the mechanism of the unconventional minus-end-directed motility differs fundamentally from that of plus-end-directed stepping. Using force spectroscopy, we have measured here the forces that ensembles of purified budding yeast kinesin-5 Cin8 produce in microtubule gliding assays in both plus- and minus-end direction. Correlation analysis of pause forces demonstrated that individual Cin8 molecules produce additive forces in both directions of movement. In ensembles, Cin8 motors were able to produce single-motor forces up to a magnitude of ∼1.5 pN. Hence, these properties appear to be conserved within the kinesin-5 subfamily. Force production was largely independent of the directionality of movement, indicating similarities between the motility mechanisms for both directions. These results provide constraints for the development of models for the bidirectional motility mechanism of fission yeast kinesin-5 and provide insight into the function of this mitotic motor.
AU - Fallesen, Todd
AU - Roostalu, Johanna
AU - Düllberg, Christian F
AU - Pruessner, Gunnar
AU - Surrey, Thomas
ID - 453
IS - 9
JF - Biophysical Journal
TI - Ensembles of bidirectional kinesin Cin8 produce additive forces in both directions of movement
VL - 113
ER -
TY - JOUR
AB - The social insects bees, wasps, ants, and termites are species-rich, occur in many habitats, and often constitute a large part of the biomass. Many are also invasive, including species of termites, the red imported fire ant, and the Argentine ant. While invasive social insects have been a problem in Southern Europe for some time, Central Europa was free of invasive ant species until recently because most ants are adapted to warmer climates. Only in the 1990s, did Lasius neglectus, a close relative of the common black garden ant, arrive in Germany. First described in 1990 based on individuals collected in Budapest, the species has since been detected for example in France, Germany, Spain, England, and Kyrgyzstan. The species is spread with soil during construction work or plantings, and L. neglectus therefore is often found in parks and botanical gardens. Another invasive ant now spreading in southern Germany is Formica fuscocinerea, which occurs along rivers, including in the sandy floodplains of the river Isar. As is typical of pioneer species, F. fuscocinerea quickly becomes extremely abundant and therefore causes problems for example on playgrounds in Munich. All invasive ant species are characterized by cooperation across nests, leading to strongly interconnected, very large super-colonies. The resulting dominance results in the extinction of native ant species as well as other arthropod species and thus in the reduction of biodiversity.
AU - Cremer, Sylvia
ID - 459
JF - Rundgespräche Forum Ökologie
TI - Invasive Ameisen in Europa: Wie sie sich ausbreiten und die heimische Fauna verändern
VL - 46
ER -
TY - CONF
AB - Tunneling of a particle through a potential barrier remains one of the most remarkable quantum phenomena. Owing to advances in laser technology, electric fields comparable to those electrons experience in atoms are readily generated and open opportunities to dynamically investigate the process of electron tunneling through the potential barrier formed by the superposition of both laser and atomic fields. Attosecond-time and angstrom-space resolution of the strong laser-field technique allow to address fundamental questions related to tunneling, which are still open and debated: Which time is spent under the barrier and what momentum is picked up by the particle in the meantime? In this combined experimental and theoretical study we demonstrate that for strong-field ionization the leading quantum mechanical Wigner treatment for the time resolved description of tunneling is valid. We achieve a high sensitivity on the tunneling barrier and unambiguously isolate its effects by performing a differential study of two systems with almost identical tunneling geometry. Moreover, working with a low frequency laser, we essentially limit the non-adiabaticity of the process as a major source of uncertainty. The agreement between experiment and theory implies two substantial corrections with respect to the widely employed quasiclassical treatment: In addition to a non-vanishing longitudinal momentum along the laser field-direction we provide clear evidence for a non-zero tunneling time delay. This addresses also the fundamental question how the transition occurs from the tunnel barrier to free space classical evolution of the ejected electron.
AU - Camus, Nicolas
AU - Yakaboylu, Enderalp
AU - Fechner, Lutz
AU - Klaiber, Michael
AU - Laux, Martin
AU - Mi, Yonghao
AU - Hatsagortsyan, Karen
AU - Pfeifer, Thomas
AU - Keitel, Cristoph
AU - Moshammer, Robert
ID - 313
IS - 1
SN - 17426588
TI - Experimental evidence for Wigner's tunneling time
VL - 999
ER -
TY - THES
AB - Bacteria and their pathogens – phages – are the most abundant living entities on Earth. Throughout their coevolution, bacteria have evolved multiple immune systems to overcome the ubiquitous threat from the phages. Although the molecu- lar details of these immune systems’ functions are relatively well understood, their epidemiological consequences for the phage-bacterial communities have been largely neglected. In this thesis we employed both experimental and theoretical methods to explore whether herd and social immunity may arise in bacterial popu- lations. Using our experimental system consisting of Escherichia coli strains with a CRISPR based immunity to the T7 phage we show that herd immunity arises in phage-bacterial communities and that it is accentuated when the populations are spatially structured. By fitting a mathematical model, we inferred expressions for the herd immunity threshold and the velocity of spread of a phage epidemic in partially resistant bacterial populations, which both depend on the bacterial growth rate, phage burst size and phage latent period. We also investigated the poten- tial for social immunity in Streptococcus thermophilus and its phage 2972 using a bioinformatic analysis of potentially coding short open reading frames with a signalling signature, encoded within the CRISPR associated genes. Subsequently, we tested one identified potentially signalling peptide and found that its addition to a phage-challenged culture increases probability of survival of bacteria two fold, although the results were only marginally significant. Together, these results demonstrate that the ubiquitous arms races between bacteria and phages have further consequences at the level of the population.
AU - Payne, Pavel
ID - 6291
TI - Bacterial herd and social immunity to phages
ER -
TY - THES
AB - Plant hormone auxin and its transport between cells belong to the most important
mechanisms controlling plant development. Auxin itself could change localization of PINs and
thereby control direction of its own flow. We performed an expression profiling experiment
in Arabidopsis roots to identify potential regulators of PIN polarity which are transcriptionally
regulated by auxin signalling. We identified several novel regulators and performed a detailed
characterization of the transcription factor WRKY23 (At2g47260) and its role in auxin
feedback on PIN polarity. Gain-of-function and dominant-negative mutants revealed that
WRKY23 plays a crucial role in mediating the auxin effect on PIN polarity. In concordance,
typical polar auxin transport processes such as gravitropism and leaf vascular pattern
formation were disturbed by interfering with WRKY23 function.
In order to identify direct targets of WRKY23, we performed consequential expression
profiling experiments using a WRKY23 inducible gain-of-function line and dominant-negative
WRKY23 line that is defunct in PIN re-arrangement. Among several genes mostly related to
the groups of cell wall and defense process regulators, we identified LYSINE-HISTIDINE
TRANSPORTER 1 (LHT1; At5g40780), a small amino acid permease gene from the amino
acid/auxin permease family (AAAP), we present its detailed characterisation in auxin feedback
on PIN repolarization, identified its transcriptional regulation, we propose a potential
mechanism of its action. Moreover, we identified also a member of receptor-like protein
kinase LRR-RLK (LEUCINE-RICH REPEAT TRANSMEMBRANE PROTEIN KINASE PROTEIN 1;
LRRK1; At1g05700), which also affects auxin-dependent PIN re-arrangement. We described
its transcriptional behaviour, subcellular localization. Based on global expression data, we
tried to identify ligand responsible for mechanism of signalling and suggest signalling partner
and interactors. Additionally, we described role of novel phytohormone group, strigolactone,
in auxin-dependent PIN re-arrangement, that could be a fundament for future studies in this
field.
Our results provide first insights into an auxin transcriptional network targeting PIN
localization and thus regulating plant development. We highlighted WRKY23 transcriptional
network and characterised its mediatory role in plant development. We identified direct
effectors of this network, LHT1 and LRRK1, and describe their roles in PIN re-arrangement and
PIN-dependent auxin transport processes.
AU - Prat, Tomas
ID - 1127
TI - Identification of novel regulators of PIN polarity and development of novel auxin sensor
ER -
TY - JOUR
AB - Plant meristems carry pools of continuously active stem cells, whose activity is controlled by developmental and environmental signals. After stem cell division, daughter cells that exit the stem cell domain acquire transit amplifying cell identity before they are incorporated into organs and differentiate. In this study, we used an integrated approach to elucidate the role of HECATE (HEC) genes in regulating developmental trajectories of shoot stem cells in Arabidopsis thaliana. Our work reveals that HEC function stabilizes cell fate in distinct zones of the shoot meristem thereby controlling the spatio-temporal dynamics of stem cell differentiation. Importantly, this activity is concomitant with the local modulation of cellular responses to cytokinin and auxin, two key phytohormones regulating cell behaviour. Mechanistically, we show that HEC factors transcriptionally control and physically interact with MONOPTEROS (MP), a key regulator of auxin signalling, and modulate the autocatalytic stabilization of auxin signalling output.
AU - Gaillochet, Christophe
AU - Stiehl, Thomas
AU - Wenzl, Christian
AU - Ripoll, Juan-José
AU - Bailey-Steinitz, Lindsay J
AU - Li, Lanxin
AU - Pfeiffer, Anne
AU - Miotk, Andrej
AU - Hakenjos, Jana P
AU - Forner, Joachim
AU - Yanofsky, Martin F
AU - Marciniak-Czochra, Anna
AU - Lohmann, Jan U
ID - 9190
JF - eLife
SN - 2050-084X
TI - Control of plant cell fate transitions by transcriptional and hormonal signals
VL - 6
ER -
TY - CONF
AB - In multi-task learning, a learner is given a collection of prediction tasks and needs to solve all of them. In contrast to previous work, which required that annotated training data must be available for all tasks, we consider a new setting, in which for some tasks, potentially most of them, only unlabeled training data is provided. Consequently, to solve all tasks, information must be transferred between tasks with labels and tasks without labels. Focusing on an instance-based transfer method we analyze two variants of this setting: when the set of labeled tasks is fixed, and when it can be actively selected by the learner. We state and prove a generalization bound that covers both scenarios and derive from it an algorithm for making the choice of labeled tasks (in the active case) and for transferring information between the tasks in a principled way. We also illustrate the effectiveness of the algorithm on synthetic and real data.
AU - Pentina, Anastasia
AU - Lampert, Christoph
ID - 999
SN - 9781510855144
TI - Multi-task learning with labeled and unlabeled tasks
VL - 70
ER -
TY - JOUR
AB - We generalize winning conditions in two-player games by adding a structural acceptance condition called obligations. Obligations are orthogonal to the linear winning conditions that define whether a play is winning. Obligations are a declaration that player 0 can achieve a certain value from a configuration. If the obligation is met, the value of that configuration for player 0 is 1. We define the value in such games and show that obligation games are determined. For Markov chains with Borel objectives and obligations, and finite turn-based stochastic parity games with obligations we give an alternative and simpler characterization of the value function. Based on this simpler definition we show that the decision problem of winning finite turn-based stochastic parity games with obligations is in NP∩co-NP. We also show that obligation games provide a game framework for reasoning about p-automata. © 2017 The Association for Symbolic Logic.
AU - Chatterjee, Krishnendu
AU - Piterman, Nir
ID - 684
IS - 2
JF - Journal of Symbolic Logic
SN - 0022-4812
TI - Obligation blackwell games and p-automata
VL - 82
ER -
TY - JOUR
AB - Cytosine methylation regulates essential genome functions across eukaryotes, but the fundamental question of whether nucleosomal or naked DNA is the preferred substrate of plant and animal methyltransferases remains unresolved. Here, we show that genetic inactivation of a single DDM1/Lsh family nucleosome remodeler biases methylation toward inter-nucleosomal linker DNA in Arabidopsis thaliana and mouse. We find that DDM1 enables methylation of DNA bound to the nucleosome, suggesting that nucleosome-free DNA is the preferred substrate of eukaryotic methyltransferases in vivo. Furthermore, we show that simultaneous mutation of DDM1 and linker histone H1 in Arabidopsis reproduces the strong linker-specific methylation patterns of species that diverged from flowering plants and animals over a billion years ago. Our results indicate that in the absence of remodeling, nucleosomes are strong barriers to DNA methyltransferases. Linker-specific methylation can evolve simply by breaking the connection between nucleosome remodeling and DNA methylation.
AU - Lyons, David B
AU - ZILBERMAN, Daniel
ID - 9445
JF - eLife
TI - DDM1 and Lsh remodelers allow methylation of DNA wrapped in nucleosomes
VL - 6
ER -
TY - JOUR
AB - Methylation in the bodies of active genes is common in animals and vascular plants. Evolutionary patterns indicate homeostatic functions for this type of methylation.
AU - ZILBERMAN, Daniel
ID - 9506
IS - 1
JF - Genome Biology
SN - 1474-760X
TI - An evolutionary case for functional gene body methylation in plants and animals
VL - 18
ER -
TY - JOUR
AB - RNA Polymerase II pauses and backtracks during transcription, with many consequences for gene expression and cellular physiology. Here, we show that the energy required to melt double-stranded nucleic acids in the transcription bubble predicts pausing in Saccharomyces cerevisiae far more accurately than nucleosome roadblocks do. In addition, the same energy difference also determines when the RNA polymerase backtracks instead of continuing to move forward. This data-driven model corroborates—in a genome wide and quantitative manner—previous evidence that sequence-dependent thermodynamic features of nucleic acids influence both transcriptional pausing and backtracking.
AU - Lukacisin, Martin
AU - Landon, Matthieu
AU - Jajoo, Rishi
ID - 1029
IS - 3
JF - PLoS One
SN - 19326203
TI - Sequence-specific thermodynamic properties of nucleic acids influence both transcriptional pausing and backtracking in yeast
VL - 12
ER -
TY - JOUR
AB - Left-right asymmetry is a fundamental feature of higher-order brain structure; however, the molecular basis of brain asymmetry remains unclear. We recently identified structural and functional asymmetries in mouse hippocampal circuitry that result from the asymmetrical distribution of two distinct populations of pyramidal cell synapses that differ in the density of the NMDA receptor subunit GluRε2 (also known as NR2B, GRIN2B or GluN2B). By examining the synaptic distribution of ε2 subunits, we previously found that β2-microglobulin-deficient mice, which lack cell surface expression of the vast majority of major histocompatibility complex class I (MHCI) proteins, do not exhibit circuit asymmetry. In the present study, we conducted electrophysiological and anatomical analyses on the hippocampal circuitry of mice with a knockout of the paired immunoglobulin-like receptor B (PirB), an MHCI receptor. As in β2-microglobulin-deficient mice, the PirB-deficient hippocampus lacked circuit asymmetries. This finding that MHCI loss-of-function mice and PirB knockout mice have identical phenotypes suggests that MHCI signals that produce hippocampal asymmetries are transduced through PirB. Our results provide evidence for a critical role of the MHCI/PirB signaling system in the generation of asymmetries in hippocampal circuitry.
AU - Ukai, Hikari
AU - Kawahara, Aiko
AU - Hirayama, Keiko
AU - Case, Matthew J
AU - Aino, Shotaro
AU - Miyabe, Masahiro
AU - Wakita, Ken
AU - Oogi, Ryohei
AU - Kasayuki, Michiyo
AU - Kawashima, Shihomi
AU - Sugimoto, Shunichi
AU - Chikamatsu, Kanako
AU - Nitta, Noritaka
AU - Koga, Tsuneyuki
AU - Shigemoto, Ryuichi
AU - Takai, Toshiyuki
AU - Ito, Isao
ID - 682
IS - 6
JF - PLoS One
SN - 19326203
TI - PirB regulates asymmetries in hippocampal circuitry
VL - 12
ER -
TY - JOUR
AB - Mutator strains are expected to evolve when the availability and effect of beneficial mutations are high enough to counteract the disadvantage from deleterious mutations that will inevitably accumulate. As the population becomes more adapted to its environment, both availability and effect of beneficial mutations necessarily decrease and mutation rates are predicted to decrease. It has been shown that certain molecular mechanisms can lead to increased mutation rates when the organism finds itself in a stressful environment. While this may be a correlated response to other functions, it could also be an adaptive mechanism, raising mutation rates only when it is most advantageous. Here, we use a mathematical model to investigate the plausibility of the adaptive hypothesis. We show that such a mechanism can be mantained if the population is subjected to diverse stresses. By simulating various antibiotic treatment schemes, we find that combination treatments can reduce the effectiveness of second-order selection on stress-induced mutagenesis. We discuss the implications of our results to strategies of antibiotic therapy.
AU - Lukacisinova, Marta
AU - Novak, Sebastian
AU - Paixao, Tiago
ID - 696
IS - 7
JF - PLoS Computational Biology
SN - 1553734X
TI - Stress induced mutagenesis: Stress diversity facilitates the persistence of mutator genes
VL - 13
ER -
TY - JOUR
AB - The rising prevalence of antibiotic resistant bacteria is an increasingly serious public health challenge. To address this problem, recent work ranging from clinical studies to theoretical modeling has provided valuable insights into the mechanisms of resistance, its emergence and spread, and ways to counteract it. A deeper understanding of the underlying dynamics of resistance evolution will require a combination of experimental and theoretical expertise from different disciplines and new technology for studying evolution in the laboratory. Here, we review recent advances in the quantitative understanding of the mechanisms and evolution of antibiotic resistance. We focus on key theoretical concepts and new technology that enables well-controlled experiments. We further highlight key challenges that can be met in the near future to ultimately develop effective strategies for combating resistance.
AU - Lukacisinova, Marta
AU - Bollenbach, Mark Tobias
ID - 1027
JF - Current Opinion in Biotechnology
TI - Toward a quantitative understanding of antibiotic resistance evolution
VL - 46
ER -
TY - JOUR
AB - The history of auxin and cytokinin biology including the initial discoveries by father–son duo Charles Darwin and Francis Darwin (1880), and Gottlieb Haberlandt (1919) is a beautiful demonstration of unceasing continuity of research. Novel findings are integrated into existing hypotheses and models and deepen our understanding of biological principles. At the same time new questions are triggered and hand to hand with this new methodologies are developed to address these new challenges.
AU - Hurny, Andrej
AU - Benková, Eva
ID - 1024
JF - Auxins and Cytokinins in Plant Biology
SN - 10643745
TI - Methodological advances in auxin and cytokinin biology
VL - 1569
ER -
TY - JOUR
AB - How the organization of genes on a chromosome shapes adaptation is essential for understanding evolutionary paths. Here, we investigate how adaptation to rapidly increasing levels of antibiotic depends on the chromosomal neighborhood of a drug-resistance gene inserted at different positions of the Escherichia coli chromosome. Using a dual-fluorescence reporter that allows us to distinguish gene amplifications from other up-mutations, we track in real-time adaptive changes in expression of the drug-resistance gene. We find that the relative contribution of several mutation types differs systematically between loci due to properties of neighboring genes: essentiality, expression, orientation, termination, and presence of duplicates. These properties determine rate and fitness effects of gene amplification, deletions, and mutations compromising transcriptional termination. Thus, the adaptive potential of a gene under selection is a system-property with a complex genetic basis that is specific for each chromosomal locus, and it can be inferred from detailed functional and genomic data.
AU - Steinrück, Magdalena
AU - Guet, Calin C
ID - 704
JF - eLife
SN - 2050084X
TI - Complex chromosomal neighborhood effects determine the adaptive potential of a gene under selection
VL - 6
ER -
TY - JOUR
AB - The segregation of different cell types into distinct tissues is a fundamental process in metazoan development. Differences in cell adhesion and cortex tension are commonly thought to drive cell sorting by regulating tissue surface tension (TST). However, the role that differential TST plays in cell segregation within the developing embryo is as yet unclear. Here, we have analyzed the role of differential TST for germ layer progenitor cell segregation during zebrafish gastrulation. Contrary to previous observations that differential TST drives germ layer progenitor cell segregation in vitro, we show that germ layers display indistinguishable TST within the gastrulating embryo, arguing against differential TST driving germ layer progenitor cell segregation in vivo. We further show that the osmolarity of the interstitial fluid (IF) is an important factor that influences germ layer TST in vivo, and that lower osmolarity of the IF compared with standard cell culture medium can explain why germ layers display differential TST in culture but not in vivo. Finally, we show that directed migration of mesendoderm progenitors is required for germ layer progenitor cell segregation and germ layer formation.
AU - Krens, Gabriel
AU - Veldhuis, Jim
AU - Barone, Vanessa
AU - Capek, Daniel
AU - Maître, Jean-Léon
AU - Brodland, Wayne
AU - Heisenberg, Carl-Philipp J
ID - 676
IS - 10
JF - Development
SN - 09501991
TI - Interstitial fluid osmolarity modulates the action of differential tissue surface tension in progenitor cell segregation during gastrulation
VL - 144
ER -
TY - JOUR
AB - During embryonic development, mechanical forces are essential for cellular rearrangements driving tissue morphogenesis. Here, we show that in the early zebrafish embryo, friction forces are generated at the interface between anterior axial mesoderm (prechordal plate, ppl) progenitors migrating towards the animal pole and neurectoderm progenitors moving in the opposite direction towards the vegetal pole of the embryo. These friction forces lead to global rearrangement of cells within the neurectoderm and determine the position of the neural anlage. Using a combination of experiments and simulations, we show that this process depends on hydrodynamic coupling between neurectoderm and ppl as a result of E-cadherin-mediated adhesion between those tissues. Our data thus establish the emergence of friction forces at the interface between moving tissues as a critical force-generating process shaping the embryo.
AU - Smutny, Michael
AU - Ákos, Zsuzsa
AU - Grigolon, Silvia
AU - Shamipour, Shayan
AU - Ruprecht, Verena
AU - Capek, Daniel
AU - Behrndt, Martin
AU - Papusheva, Ekaterina
AU - Tada, Masazumi
AU - Hof, Björn
AU - Vicsek, Tamás
AU - Salbreux, Guillaume
AU - Heisenberg, Carl-Philipp J
ID - 661
JF - Nature Cell Biology
SN - 14657392
TI - Friction forces position the neural anlage
VL - 19
ER -
TY - CONF
AB - The notion of treewidth of graphs has been exploited for faster algorithms for several problems arising in verification and program analysis. Moreover, various notions of balanced tree decompositions have been used for improved algorithms supporting dynamic updates and analysis of concurrent programs. In this work, we present a tool for constructing tree-decompositions of CFGs obtained from Java methods, which is implemented as an extension to the widely used Soot framework. The experimental results show that our implementation on real-world Java benchmarks is very efficient. Our tool also provides the first implementation for balancing tree-decompositions. In summary, we present the first tool support for exploiting treewidth in the static analysis problems on Java programs.
AU - Chatterjee, Krishnendu
AU - Goharshady, Amir
AU - Pavlogiannis, Andreas
ED - D'Souza, Deepak
ID - 949
SN - 03029743
TI - JTDec: A tool for tree decompositions in soot
VL - 10482
ER -
TY - CONF
AB - We study the problem of developing efficient approaches for proving worst-case bounds of non-deterministic recursive programs. Ranking functions are sound and complete for proving termination and worst-case bounds of non-recursive programs. First, we apply ranking functions to recursion, resulting in measure functions, and show that they provide a sound and complete approach to prove worst-case bounds of non-deterministic recursive programs. Our second contribution is the synthesis of measure functions in non-polynomial forms. We show that non-polynomial measure functions with logarithm and exponentiation can be synthesized through abstraction of logarithmic or exponentiation terms, Farkas’ Lemma, and Handelman’s Theorem using linear programming. While previous methods obtain worst-case polynomial bounds, our approach can synthesize bounds of the form O(n log n) as well as O(nr) where r is not an integer. We present experimental results to demonstrate that our approach can efficiently obtain worst-case bounds of classical recursive algorithms such as Merge-Sort, Closest-Pair, Karatsuba’s algorithm and Strassen’s algorithm.
AU - Chatterjee, Krishnendu
AU - Fu, Hongfei
AU - Goharshady, Amir
ED - Majumdar, Rupak
ED - Kunčak, Viktor
ID - 639
SN - 978-331963389-3
TI - Non-polynomial worst case analysis of recursive programs
VL - 10427
ER -
TY - JOUR
AB - Consider the sum X(ξ)=∑ni=1aiξi, where a=(ai)ni=1 is a sequence of non-zero reals and ξ=(ξi)ni=1 is a sequence of i.i.d. Rademacher random variables (that is, Pr[ξi=1]=Pr[ξi=−1]=1/2). The classical Littlewood-Offord problem asks for the best possible upper bound on the concentration probabilities Pr[X=x]. In this paper we study a resilience version of the Littlewood-Offord problem: how many of the ξi is an adversary typically allowed to change without being able to force concentration on a particular value? We solve this problem asymptotically, and present a few interesting open problems.
AU - Bandeira, Afonso S.
AU - Ferber, Asaf
AU - Kwan, Matthew Alan
ID - 9574
JF - Electronic Notes in Discrete Mathematics
SN - 1571-0653
TI - Resilience for the Littlewood-Offord problem
VL - 61
ER -
TY - JOUR
AB - Consider the sum X(ξ)=∑ni=1aiξi , where a=(ai)ni=1 is a sequence of non-zero reals and ξ=(ξi)ni=1 is a sequence of i.i.d. Rademacher random variables (that is, Pr[ξi=1]=Pr[ξi=−1]=1/2 ). The classical Littlewood-Offord problem asks for the best possible upper bound on the concentration probabilities Pr[X=x] . In this paper we study a resilience version of the Littlewood-Offord problem: how many of the ξi is an adversary typically allowed to change without being able to force concentration on a particular value? We solve this problem asymptotically, and present a few interesting open problems.
AU - Bandeira, Afonso S.
AU - Ferber, Asaf
AU - Kwan, Matthew Alan
ID - 9588
JF - Advances in Mathematics
SN - 0001-8708
TI - Resilience for the Littlewood–Offord problem
VL - 319
ER -
TY - JOUR
AB - For any number field we calculate the exact proportion of rational numbers which are everywhere locally a norm but not globally a norm from the number field.
AU - Timothy Browning
AU - Newton, Rachel
ID - 262
IS - 2
JF - Mathematika
TI - The proportion of failures of the Hasse norm principle
VL - 62
ER -
TY - JOUR
AB - We count rational points of bounded height on the Cayley ruled cubic surface and interpret the result in the context of general conjectures due to Batyrev and Tschinkel.
AU - de la Bretèche, Régis
AU - Timothy Browning
AU - Salberger, Per
ID - 263
IS - 1
JF - European Journal of Mathematics
TI - Counting rational points on the Cayley ruled cubic
VL - 2
ER -
TY - JOUR
AB - Given a family of varieties over a number field, we determine conditions under which there is a Brauer-Manin obstruction to weak approximation for 100% of the fibres which are everywhere locally soluble.
AU - Bright, Maritn J
AU - Timothy Browning
AU - Loughran, Daniel
ID - 264
IS - 7
JF - Compositio Mathematica
TI - Failures of weak approximation in families
VL - 152
ER -
TY - JOUR
AB - Balance of cortical excitation and inhibition (EI) is thought to be disrupted in several neuropsychiatric conditions, yet it is not clear how it is maintained in the healthy human brain. When EI balance is disturbed during learning and memory in animal models, it can be restabilized via formation of inhibitory replicas of newly formed excitatory connections. Here we assess evidence for such selective inhibitory rebalancing in humans. Using fMRI repetition suppression we measure newly formed cortical associations in the human brain. We show that expression of these associations reduces over time despite persistence in behavior, consistent with inhibitory rebalancing. To test this, we modulated excitation/inhibition balance with transcranial direct current stimulation (tDCS). Using ultra-high-field (7T) MRI and spectroscopy, we show that reducing GABA allows cortical associations to be re-expressed. This suggests that in humans associative memories are stored in balanced excitatory-inhibitory ensembles that lie dormant unless latent inhibitory connections are unmasked.
AU - Barron, H.C.
AU - Vogels, Tim P
AU - Emir, U.E.
AU - Makin, T.R.
AU - O’Shea, J.
AU - Clare, S.
AU - Jbabdi, S.
AU - Dolan, R.J.
AU - Behrens, T.E.J.
ID - 8020
IS - 1
JF - Neuron
SN - 0896-6273
TI - Unmasking latent inhibitory connections in human cortex to reveal dormant cortical memories
VL - 90
ER -
TY - CONF
AB - With the accelerated development of robot technologies, optimal control becomes one of the central themes of research. In traditional approaches, the controller, by its internal functionality, finds appropriate actions on the basis of the history of sensor values, guided by the goals, intentions, objectives, learning schemes, and so forth. The idea is that the controller controls the world---the body plus its environment---as reliably as possible. This paper focuses on new lines of self-organization for developmental robotics. We apply the recently developed differential extrinsic synaptic plasticity to a muscle-tendon driven arm-shoulder system from the Myorobotics toolkit. In the experiments, we observe a vast variety of self-organized behavior patterns: when left alone, the arm realizes pseudo-random sequences of different poses. By applying physical forces, the system can be entrained into definite motion patterns like wiping a table. Most interestingly, after attaching an object, the controller gets in a functional resonance with the object's internal dynamics, starting to shake spontaneously bottles half-filled with water or sensitively driving an attached pendulum into a circular mode. When attached to the crank of a wheel the neural system independently discovers how to rotate it. In this way, the robot discovers affordances of objects its body is interacting with.
AU - Martius, Georg S
AU - Hostettler, Rafael
AU - Knoll, Alois
AU - Der, Ralf
ID - 8094
SN - 9780262339360
T2 - Proceedings of the Artificial Life Conference 2016
TI - Self-organized control of an tendon driven arm by differential extrinsic plasticity
VL - 28
ER -
TY - GEN
AB - The stimulus selectivity of synaptic currents in cortical neurons often shows a co-tuning of excitation and inhibition, but the mechanisms that underlie the emergence and plasticity of this co-tuning are not fully understood. Using a computational model, we show that an interaction of excitatory and inhibitory synaptic plasticity reproduces both the developmental and – when combined with a disinhibitory gate – the adult plasticity of excitatory and inhibitory receptive fields in auditory cortex. The co-tuning arises from inhibitory plasticity that balances excitation and inhibition, while excitatory stimulus selectivity can result from two different mechanisms. Inhibitory inputs with a broad stimulus tuning introduce a sliding threshold as in Bienenstock-Cooper-Munro rules, introducing an excitatory stimulus selectivity at the cost of a broader inhibitory receptive field. Alternatively, input asymmetries can be amplified by synaptic competition. The latter leaves any receptive field plasticity transient, a prediction we verify in recordings in auditory cortex.
AU - Clopath, Claudia
AU - Vogels, Tim P
AU - Froemke, Robert C.
AU - Sprekeler, Henning
ID - 8128
T2 - bioRxiv
TI - Receptive field formation by interacting excitatory and inhibitory synaptic plasticity
ER -
TY - JOUR
AB - Background: Anticancer vaccines could represent a valuable complementary strategy to established therapies, especially in settings of early stage and minimal residual disease. HER-2 is an important target for immunotherapy and addressed by the monoclonal antibody trastuzumab. We have previously generated HER-2 mimotope peptides from phage display libraries. The synthesized peptides were coupled to carriers and applied for epitope-specific induction of trastuzumab-like IgG. For simplification and to avoid methodological limitations of synthesis and coupling chemistry, we herewith present a novel and optimized approach by using adeno-associated viruses (AAV) as effective and high-density mimotope-display system, which can be directly used for vaccination. Methods: An AAV capsid display library was constructed by genetically incorporating random peptides in a plasmid encoding the wild-type AAV2 capsid protein. AAV clones, expressing peptides specifically reactive to trastuzumab, were employed to immunize BALB/c mice. Antibody titers against human HER-2 were determined, and the isotype composition and functional properties of these were tested. Finally, prophylactically immunized mice were challenged with human HER-2 transfected mouse D2F2/E2 cells. Results: HER-2 mimotope AAV-vaccines induced antibodies specific to human HER-2. Two clones were selected for immunization of mice, which were subsequently grafted D2F2/E2 cells. Both mimotope AAV clones delayed the growth of tumors significantly, as compared to controls. Conclusion: In this study, a novel mimotope AAV-based platform was created allowing the isolation of mimotopes, which can be directly used as anticancer vaccines. The example of trastuzumab AAV-mimotopes demonstrates that this vaccine strategy could help to establish active immunotherapy for breast-cancer patients.
AU - Singer, Josef
AU - Manzano-Szalai, Krisztina
AU - Fazekas, Judit
AU - Thell, Kathrin
AU - Bentley-Lukschal, Anna
AU - Stremnitzer, Caroline
AU - Roth-Walter, Franziska
AU - Weghofer, Margit
AU - Ritter, Mirko
AU - Pino Tossi, Kerstin
AU - Hörer, Markus
AU - Michaelis, Uwe
AU - Jensen-Jarolim, Erika
ID - 8241
IS - 7
JF - OncoImmunology
SN - 2162-402X
TI - Proof of concept study with an HER-2 mimotope anticancer vaccine deduced from a novel AAV-mimotope library platform
VL - 5
ER -
TY - CONF
AB - While showing great promise, Bitcoin requires users to wait tens of minutes for transactions to commit, and even then, offering only probabilistic guarantees. This paper introduces ByzCoin, a novel Byzantine consensus protocol that leverages scalable collective signing to commit Bitcoin transactions irreversibly within seconds. ByzCoin achieves Byzantine consensus while preserving Bitcoin’s open membership by dynamically forming hash power-proportionate consensus groups that represent recently-successful block miners. ByzCoin employs communication trees to optimize transaction commitment and verification under normal operation while guaranteeing safety and liveness under Byzantine faults, up to a near-optimal tolerance of f faulty group members among 3f + 2 total. ByzCoin mitigates double spending and selfish mining attacks by producing collectively signed transaction blocks within one minute of transaction submission. Tree-structured communication further reduces this latency to less than 30 seconds. Due to these optimizations, ByzCoin achieves a throughput higher than Paypal currently handles, with a confirmation latency of 15-20 seconds.
AU - Kokoris Kogias, Eleftherios
AU - Jovanovic, Philipp
AU - Gailly, Nicolas
AU - Khoffi, Ismail
AU - Gasser, Linus
AU - Ford, Bryan
ID - 8302
SN - 9781931971324
T2 - Proceedings of the 25th USENIX Conference on Security Symposium
TI - Enhancing bitcoin security and performance with strong consistency via collective signing
ER -
TY - JOUR
AB - Hybrid systems represent an important and powerful formalism for modeling real-world applications such as embedded systems. A verification tool like SpaceEx is based on the exploration of a symbolic search space (the region space). As a verification tool, it is typically optimized towards proving the absence of errors. In some settings, e.g., when the verification tool is employed in a feedback-directed design cycle, one would like to have the option to call a version that is optimized towards finding an error trajectory in the region space. A recent approach in this direction is based on guided search. Guided search relies on a cost function that indicates which states are promising to be explored, and preferably explores more promising states first. In this paper, we propose an abstraction-based cost function based on coarse-grained space abstractions for guiding the reachability analysis. For this purpose, a suitable abstraction technique that exploits the flexible granularity of modern reachability analysis algorithms is introduced. The new cost function is an effective extension of pattern database approaches that have been successfully applied in other areas. The approach has been implemented in the SpaceEx model checker. The evaluation shows its practical potential.
AU - Bogomolov, Sergiy
AU - Donzé, Alexandre
AU - Frehse, Goran
AU - Grosu, Radu
AU - Johnson, Taylor
AU - Ladan, Hamed
AU - Podelski, Andreas
AU - Wehrle, Martin
ID - 1705
IS - 4
JF - International Journal on Software Tools for Technology Transfer
TI - Guided search for hybrid systems based on coarse-grained space abstractions
VL - 18
ER -
TY - JOUR
AB - We calculate admissible values of r such that a square-free polynomial with integer coefficients, no fixed prime divisor and irreducible factors of degree at most 3 takes infinitely many values that are a product of at most r distinct primes.
AU - Browning, Timothy D
AU - Booker, Andrew
ID - 173
JF - Discrete Analysis
TI - Square-free values of reducible polynomials
VL - 8
ER -
TY - JOUR
AB - We consider Conditional random fields (CRFs) with pattern-based potentials defined on a chain. In this model the energy of a string (labeling) (Formula presented.) is the sum of terms over intervals [i, j] where each term is non-zero only if the substring (Formula presented.) equals a prespecified pattern w. Such CRFs can be naturally applied to many sequence tagging problems. We present efficient algorithms for the three standard inference tasks in a CRF, namely computing (i) the partition function, (ii) marginals, and (iii) computing the MAP. Their complexities are respectively (Formula presented.), (Formula presented.) and (Formula presented.) where L is the combined length of input patterns, (Formula presented.) is the maximum length of a pattern, and D is the input alphabet. This improves on the previous algorithms of Ye et al. (NIPS, 2009) whose complexities are respectively (Formula presented.), (Formula presented.) and (Formula presented.), where (Formula presented.) is the number of input patterns. In addition, we give an efficient algorithm for sampling, and revisit the case of MAP with non-positive weights.
AU - Kolmogorov, Vladimir
AU - Takhanov, Rustem
ID - 1794
IS - 1
JF - Algorithmica
TI - Inference algorithms for pattern-based CRFs on sequence data
VL - 76
ER -
TY - JOUR
AB - Relational models for contingency tables are generalizations of log-linear models, allowing effects associated with arbitrary subsets of cells in the table, and not necessarily containing the overall effect, that is, a common parameter in every cell. Similarly to log-linear models, relational models can be extended to non-negative distributions, but the extension requires more complex methods. An extended relational model is defined as an algebraic variety, and it turns out to be the closure of the original model with respect to the Bregman divergence. In the extended relational model, the MLE of the cell parameters always exists and is unique, but some of its properties may be different from those of the MLE under log-linear models. The MLE can be computed using a generalized iterative scaling procedure based on Bregman projections.
AU - Klimova, Anna
AU - Rudas, Tamás
ID - 1833
JF - Journal of Multivariate Analysis
TI - On the closure of relational models
VL - 143
ER -
TY - JOUR
AB - We consider random matrices of the form H=W+λV, λ∈ℝ+, where W is a real symmetric or complex Hermitian Wigner matrix of size N and V is a real bounded diagonal random matrix of size N with i.i.d.\ entries that are independent of W. We assume subexponential decay for the matrix entries of W and we choose λ∼1, so that the eigenvalues of W and λV are typically of the same order. Further, we assume that the density of the entries of V is supported on a single interval and is convex near the edges of its support. In this paper we prove that there is λ+∈ℝ+ such that the largest eigenvalues of H are in the limit of large N determined by the order statistics of V for λ>λ+. In particular, the largest eigenvalue of H has a Weibull distribution in the limit N→∞ if λ>λ+. Moreover, for N sufficiently large, we show that the eigenvectors associated to the largest eigenvalues are partially localized for λ>λ+, while they are completely delocalized for λ<λ+. Similar results hold for the lowest eigenvalues.
AU - Lee, Jioon
AU - Schnelli, Kevin
ID - 1881
IS - 1-2
JF - Probability Theory and Related Fields
TI - Extremal eigenvalues and eigenvectors of deformed Wigner matrices
VL - 164
ER -
TY - JOUR
AB - Kinetics of electrochemical reactions are several orders of magnitude slower in solids than in liquids as a result of the much lower ion diffusivity. Yet, the solid state maximizes the density of redox species, which is at least two orders of magnitude lower in liquids because of solubility limitations. With regard to electrochemical energy storage devices, this leads to high-energy batteries with limited power and high-power supercapacitors with a well-known energy deficiency. For such devices the ideal system should endow the liquid state with a density of redox species close to the solid state. Here we report an approach based on biredox ionic liquids to achieve bulk-like redox density at liquid-like fast kinetics. The cation and anion of these biredox ionic liquids bear moieties that undergo very fast reversible redox reactions. As a first demonstration of their potential for high-capacity/high-rate charge storage, we used them in redox supercapacitors. These ionic liquids are able to decouple charge storage from an ion-accessible electrode surface, by storing significant charge in the pores of the electrodes, to minimize self-discharge and leakage current as a result of retaining the redox species in the pores, and to raise working voltage due to their wide electrochemical window.
AU - Mourad, Eléonore
AU - Coustan, Laura
AU - Lannelongue, Pierre
AU - Zigah, Dodzi
AU - Mehdi, Ahmad
AU - Vioux, André
AU - Freunberger, Stefan Alexander
AU - Favier, Frédéric
AU - Fontaine, Olivier
ID - 7279
IS - 4
JF - Nature Materials
SN - 1476-1122
TI - Biredox ionic liquids with solid-like redox density in the liquid state for high-energy supercapacitors
VL - 16
ER -
TY - JOUR
AB - Redox mediators facilitate the oxidation of the highly insulating discharge product in metal–oxygen batteries during recharge and offer opportunities to achieve high reversible capacities. Now a design principle for selecting redox mediators that can recharge the batteries more efficiently is suggested.
AU - Freunberger, Stefan Alexander
ID - 7297
IS - 6
JF - Nature Energy
SN - 2058-7546
TI - Batteries: Charging ahead rationally
VL - 1
ER -
TY - JOUR
AB - Normal leaf margin development is important for leaf morphogenesis and contributes to diverse leaf shapes in higher plants. We here show the crucial roles of an atypical type II phosphatidylinositol 4-kinase, PI4Kγ5, in Arabidopsis leaf margin development. PI4Kγ5 presents a dynamics expression pattern along with leaf development and a T-DNA mutant lacking PI4Kγ5, pi4kγ5–1, presents serrated leaves, which is resulted from the accelerated cell division and increased auxin concentration at serration tips. Studies revealed that PI4Kγ5 interacts with and phosphorylates a membrane-bound NAC transcription factor, ANAC078. Previous studies demonstrated that membrane-bound transcription factors regulate gene transcription by undergoing proteolytic process to translocate into nucleus, and ANAC078 undergoes proteolysis by cleaving off the transmembrane region and carboxyl terminal. Western blot analysis indeed showed that ANAC078 deleting of carboxyl terminal is significantly reduced in pi4kγ5–1, indicating that PI4Kγ5 is important for the cleavage of ANAC078. This is consistent with the subcellular localization observation showing that fluorescence by GFP-ANAC078 is detected at plasma membrane but not nucleus in pi4kγ5–1 mutant and that expression of ANAC078 deleting of carboxyl terminal, driven by PI4Kγ5 promoter, could rescue the leaf serration defects of pi4kγ5–1. Further analysis showed that ANAC078 suppresses the auxin synthesis by directly binding and regulating the expression of auxin synthesis-related genes. These results indicate that PI4Kγ5 interacts with ANAC078 to negatively regulate auxin synthesis and hence influences cell proliferation and leaf development, providing informative clues for the regulation of in situ auxin synthesis and cell division, as well as the cleavage and functional mechanism of membrane-bound transcription factors.
AU - Tang, Yong
AU - Zhao, Chun-Yan
AU - Tan, Shutang
AU - Xue, Hong-Wei
ID - 7599
IS - 8
JF - PLOS Genetics
SN - 1553-7404
TI - Arabidopsis type II phosphatidylinositol 4-kinase PI4Kγ5 regulates auxin biosynthesis and leaf margin development through interacting with membrane-bound transcription factor ANAC078
VL - 12
ER -
TY - JOUR
AB - Genome-wide association studies (GWAS) have identified thousands of genetic variants associated with human complex traits. However, the genes or functional DNA elements through which these variants exert their effects on the traits are often unknown. We propose a method (called SMR) that integrates summary-level data from GWAS with data from expression quantitative trait locus (eQTL) studies to identify genes whose expression levels are associated with a complex trait because of pleiotropy. We apply the method to five human complex traits using GWAS data on up to 339,224 individuals and eQTL data on 5,311 individuals, and we prioritize 126 genes (for example, TRAF1 and ANKRD55 for rheumatoid arthritis and SNX19 and NMRAL1 for schizophrenia), of which 25 genes are new candidates; 77 genes are not the nearest annotated gene to the top associated GWAS SNP. These genes provide important leads to design future functional studies to understand the mechanism whereby DNA variation leads to complex trait variation.
AU - Zhu, Zhihong
AU - Zhang, Futao
AU - Hu, Han
AU - Bakshi, Andrew
AU - Robinson, Matthew Richard
AU - Powell, Joseph E
AU - Montgomery, Grant W
AU - Goddard, Michael E
AU - Wray, Naomi R
AU - Visscher, Peter M
AU - Yang, Jian
ID - 7737
IS - 5
JF - Nature Genetics
SN - 1061-4036
TI - Integration of summary data from GWAS and eQTL studies predicts complex trait gene targets
VL - 48
ER -
TY - JOUR
AB - Lock-free concurrent algorithms guarantee that some concurrent operation will always make progress in a finite number of steps. Yet programmers prefer to treat concurrent code as if it were wait-free, guaranteeing that all operations always make progress. Unfortunately, designing wait-free algorithms is generally a very complex task, and the resulting algorithms are not always efficient. Although obtaining efficient wait-free algorithms has been a long-time goal for the theory community, most nonblocking commercial code is only lock-free. This article suggests a simple solution to this problem.We show that for a large class of lock-free algorithms, under scheduling conditions that approximate those found in commercial hardware architectures, lock-free algorithms behave as if they are wait-free. In other words, programmers can continue to design simple lock-free algorithms instead of complex wait-free ones, and in practice, they will get wait-free progress. Our main contribution is a new way of analyzing a general class of lock-free algorithms under a stochastic scheduler. Our analysis relates the individual performance of processes to the global performance of the system using Markov chain lifting between a complex per-process chain and a simpler system progress chain. We show that lock-free algorithms are not only wait-free with probability 1 but that in fact a general subset of lock-free algorithms can be closely bounded in terms of the average number of steps required until an operation completes. To the best of our knowledge, this is the first attempt to analyze progress conditions, typically stated in relation to a worst-case adversary, in a stochastic model capturing their expected asymptotic behavior.
AU - Alistarh, Dan-Adrian
AU - Censor Hillel, Keren
AU - Shavit, Nir
ID - 786
IS - 4
JF - Journal of the ACM
TI - Are lock free concurrent algorithms practically wait free
VL - 63
ER -
TY - JOUR
AB - NF-κB signaling is a central pathway of immunity and integrates signal transduction upon a wide array of inflammatory stimuli. Noncanonical NF-κB signaling is activated by a small subset of TNF family receptors and characterized by NF-κB2/p52 transcriptional activity. The medical relevance of this pathway has recently re-emerged from the discovery of primary immunodeficiency patients that have loss-of-function mutations in the MAP3K14 gene encoding NIK. Nevertheless, knowledge of protein interactions that regulate noncanonical NF-κB signaling is sparse. Here we report a detailed state-of-the-art mass spectrometry-based protein–protein interaction network including the noncanonical NF-κB signaling nodes TRAF2, TRAF3, IKKα, NIK, and NF-κB2/p100. The value of the data set was confirmed by the identification of interactions already known to regulate this pathway. In addition, a remarkable number of novel interactors were identified. We provide validation of the novel NIK and IKKα interactor FKBP8, which may regulate processes downstream of noncanonical NF-κB signaling. To understand perturbed noncanonical NF-κB signaling in the context of misregulated NIK in disease, we also provide a differential interactome of NIK mutants that cause immunodeficiency. Altogether, this data set not only provides critical insight into how protein–protein interactions can regulate immune signaling but also offers a novel resource on noncanonical NF-κB signaling.
AU - Willmann, Katharina L
AU - Roberto Sacco
AU - Martins, Rui
AU - Garncarz, Wojciech
AU - Krolo, Ana
AU - Knapp, Sylvia
AU - Bennett, Keiryn L
AU - Boztug, Kaan
ID - 460
IS - 9
JF - Journal of Proteome Research
TI - Expanding the interactome of the noncanonical NF-κB signaling pathway
VL - 15
ER -
TY - CONF
AB - Magic: the Gathering is a game about magical combat for any number of players. Formally it is a zero-sum, imperfect information stochastic game that consists of a potentially unbounded number of steps. We consider the problem of deciding if a move is legal in a given single step of Magic. We show that the problem is (a) coNP-complete in general; and (b) in P if either of two small sets of cards are not used. Our lower bound holds even for single-player Magic games. The significant aspects of our results are as follows: First, in most real-life game problems, the task of deciding whether a given move is legal in a single step is trivial, and the computationally hard task is to find the best sequence of legal moves in the presence of multiple players. In contrast, quite uniquely our hardness result holds for single step and with only one-player. Second, we establish efficient algorithms for important special cases of Magic.
AU - Chatterjee, Krishnendu
AU - Ibsen-Jensen, Rasmus
ID - 478
TI - The complexity of deciding legality of a single step of magic: The gathering
VL - 285
ER -
TY - CONF
AB - Graph games provide the foundation for modeling and synthesizing reactive processes. In the synthesis of stochastic reactive processes, the traditional model is perfect-information stochastic games, where some transitions of the game graph are controlled by two adversarial players, and the other transitions are executed probabilistically. We consider such games where the objective is the conjunction of several quantitative objectives (specified as mean-payoff conditions), which we refer to as generalized mean-payoff objectives. The basic decision problem asks for the existence of a finite-memory strategy for a player that ensures the generalized mean-payoff objective be satisfied with a desired probability against all strategies of the opponent. A special case of the decision problem is the almost-sure problem where the desired probability is 1. Previous results presented a semi-decision procedure for -approximations of the almost-sure problem. In this work, we show that both the almost-sure problem as well as the general basic decision problem are coNP-complete, significantly improving the previous results. Moreover, we show that in the case of 1-player stochastic games, randomized memoryless strategies are sufficient and the problem can be solved in polynomial time. In contrast, in two-player stochastic games, we show that even with randomized strategies exponential memory is required in general, and present a matching exponential upper bound. We also study the basic decision problem with infinite-memory strategies and present computational complexity results for the problem. Our results are relevant in the synthesis of stochastic reactive systems with multiple quantitative requirements.
AU - Chatterjee, Krishnendu
AU - Doyen, Laurent
ID - 480
TI - Perfect-information stochastic games with generalized mean-payoff objectives
VL - 05-08-July-2016
ER -
TY - JOUR
AB - The CLE (CLAVATA3/Embryo Surrounding Region-related) peptides are small secreted signaling peptides that are primarily involved in the regulation of stem cell homeostasis in different plant meristems. Particularly, the characterization of the CLE41-PXY/TDR signaling pathway has greatly advanced our understanding on the potential roles of CLE peptides in vascular development and wood formation. Nevertheless, our knowledge on this gene family in a tree species is limited. In a recent study, we reported on a systematically investigation of the CLE gene family in Populus trichocarpa . The potential roles of PtCLE genes were studied by comparative analysis and transcriptional pro fi ling. Among fi fty PtCLE members, many PtCLE proteins share identical CLE motifs or contain the same CLE motif as that of AtCLEs, while PtCLE genes exhibited either comparable or distinct expression patterns comparing to their Arabidopsis counterparts. These fi ndings indicate the existence of both functional conservation and functional divergence between PtCLEs and their AtCLE orthologues. Our results provide valuable resources for future functional investigations of these critical signaling molecules in woody plants.
AU - Liu, Zhijun
AU - Yang, Nan
AU - Lv, Yanting
AU - Pan, Lixia
AU - Lv, Shuo
AU - Han, Huibin
AU - Wang, Guodong
ID - 510
IS - 6
JF - Plant Signaling & Behavior
TI - The CLE gene family in Populus trichocarpa
VL - 11
ER -
TY - GEN
AB - We consider the quantitative analysis problem for interprocedural control-flow graphs (ICFGs). The input consists of an ICFG, a positive weight function that assigns every transition a positive integer-valued number, and a labelling of the transitions (events) as good, bad, and neutral events. The weight function assigns to each transition a numerical value that represents ameasure of how good or bad an event is. The quantitative analysis problem asks whether there is a run of the ICFG where the ratio of the sum of the numerical weights of good events versus the sum of weights of bad events in the long-run is at least a given threshold (or equivalently, to compute the maximal ratio among all valid paths in the ICFG). The quantitative analysis problem for ICFGs can be solved in polynomial time, and we present an efficient and practical algorithm for the problem. We show that several problems relevant for static program analysis, such as estimating the worst-case execution time of a program or the average energy consumption of a mobile application, can be modeled in our framework. We have implemented our algorithm as a tool in the Java Soot framework. We demonstrate the effectiveness of our approach with two case studies. First, we show that our framework provides a sound approach (no false positives) for the analysis of inefficiently-used containers. Second, we show that our approach can also be used for static profiling of programs which reasons about methods that are frequently invoked. Our experimental results show that our tool scales to relatively large benchmarks, and discovers relevant and useful information that can be used to optimize performance of the programs.
AU - Chatterjee, Krishnendu
AU - Pavlogiannis, Andreas
AU - Velner, Yaron
ID - 5445
SN - 2664-1690
TI - Quantitative interprocedural analysis
ER -
TY - GEN
AB - We study the problem of developing efficient approaches for proving termination of recursive programs with one-dimensional arrays. Ranking functions serve as a sound and complete approach for proving termination of non-recursive programs without array operations. First, we generalize ranking functions to the notion of measure functions, and prove that measure functions (i) provide a sound method to prove termination of recursive programs (with one-dimensional arrays), and (ii) is both sound and complete over recursive programs without array operations. Our second contribution is the synthesis of measure functions of specific forms in polynomial time. More precisely, we prove that (i) polynomial measure functions over recursive programs can be synthesized in polynomial time through Farkas’ Lemma and Handelman’s Theorem, and (ii) measure functions involving logarithm and exponentiation can be synthesized in polynomial time through abstraction of logarithmic or exponential terms and Handelman’s Theorem. A key application of our method is the worst-case analysis of recursive programs. While previous methods obtain worst-case polynomial bounds of the form O(n^k), where k is an integer, our polynomial time methods can synthesize bounds of the form O(n log n), as well as O(n^x), where x is not an integer. We show the applicability of our automated technique to obtain worst-case complexity of classical recursive algorithms such as (i) Merge-Sort, the divideand-
conquer algorithm for the Closest-Pair problem, where we obtain O(n log n) worst-case bound, and (ii) Karatsuba’s algorithm for polynomial multiplication and Strassen’s algorithm for matrix multiplication, where we obtain O(n^x) bound, where x is not an integer and close to the best-known bounds for the respective algorithms. Finally, we present experimental results to demonstrate the
effectiveness of our approach.
AU - Anonymous, 1
AU - Anonymous, 2
AU - Anonymous, 3
ID - 5446
SN - 2664-1690
TI - Termination and worst-case analysis of recursive programs
ER -
TY - GEN
AB - We consider the problem of developing automated techniques to aid the average-case complexity analysis of programs. Several classical textbook algorithms have quite efficient average-case complexity, whereas the corresponding worst-case bounds are either inefficient (e.g., QUICK-SORT), or completely ineffective (e.g., COUPONCOLLECTOR). Since the main focus of average-case analysis is to obtain efficient bounds, we consider bounds that are either logarithmic,
linear, or almost-linear (O(log n), O(n), O(n · log n),
respectively, where n represents the size of the input). Our main contribution is a sound approach for deriving such average-case bounds for randomized recursive programs. Our approach is efficient (a simple linear-time algorithm), and it is based on (a) the analysis of recurrence relations induced by randomized algorithms, and (b) a guess-and-check technique. Our approach can infer the asymptotically optimal average-case bounds for classical randomized algorithms, including RANDOMIZED-SEARCH, QUICKSORT, QUICK-SELECT, COUPON-COLLECTOR, where the worstcase
bounds are either inefficient (such as linear as compared to logarithmic of average-case, or quadratic as compared to linear or almost-linear of average-case), or ineffective. We have implemented our approach, and the experimental results show that we obtain the bounds efficiently for various classical algorithms.
AU - Anonymous, 1
AU - Anonymous, 2
AU - Anonymous, 3
ID - 5447
SN - 2664-1690
TI - Average-case analysis of programs: Automated recurrence analysis for almost-linear bounds
ER -
TY - GEN
AB - We present a new dynamic partial-order reduction method for stateless model checking of concurrent programs. A common approach for exploring program behaviors relies on enumerating the traces of the program, without storing the visited states (aka stateless exploration). As the number of distinct traces grows exponentially, dynamic partial-order reduction (DPOR) techniques have been successfully used to partition the space of traces into equivalence classes (Mazurkiewicz partitioning), with the goal of exploring only few representative traces from each class.
We introduce a new equivalence on traces under sequential consistency semantics, which we call the observation equivalence. Two traces are observationally equivalent if every read event observes the same write event in both traces. While the traditional Mazurkiewicz equivalence is control-centric, our new definition is data-centric. We show that our observation equivalence is coarser than the Mazurkiewicz equivalence, and in many cases even exponentially coarser. We devise a DPOR exploration of the trace space, called data-centric DPOR, based on the observation equivalence.
1. For acyclic architectures, our algorithm is guaranteed to explore exactly one representative trace from each observation class, while spending polynomial time per class. Hence, our algorithm is optimal wrt the observation equivalence, and in several cases explores exponentially fewer traces than any enumerative method based on the Mazurkiewicz equivalence.
2. For cyclic architectures, we consider an equivalence between traces which is finer than the observation equivalence; but coarser than the Mazurkiewicz equivalence, and in some cases is exponentially coarser. Our data-centric DPOR algorithm remains optimal under this trace equivalence.
Finally, we perform a basic experimental comparison between the existing Mazurkiewicz-based DPOR and our data-centric DPOR on a set of academic benchmarks. Our results show a significant reduction in both running time and the number of explored equivalence classes.
AU - Anonymous, 1
AU - Anonymous, 2
AU - Anonymous, 3
AU - Anonymous, 4
ID - 5448
SN - 2664-1690
TI - Data-centric dynamic partial order reduction
ER -
TY - GEN
AB - The fixation probability is the probability that a new mutant introduced in a homogeneous population eventually takes over the entire population.
The fixation probability is a fundamental quantity of natural selection, and known to depend on the population structure.
Amplifiers of natural selection are population structures which increase the fixation probability of advantageous mutants, as compared to the baseline case of well-mixed populations. In this work we focus on symmetric population structures represented as undirected graphs. In the regime of undirected graphs, the strongest amplifier known has been the Star graph, and the existence of undirected graphs with stronger amplification properties has remained open for over a decade.
In this work we present the Comet and Comet-swarm families of undirected graphs. We show that for a range of fitness values of the mutants, the Comet and Comet-swarm graphs have fixation probability strictly larger than the fixation probability of the Star graph, for fixed population size and at the limit of large populations, respectively.
AU - Pavlogiannis, Andreas
AU - Tkadlec, Josef
AU - Chatterjee, Krishnendu
AU - Nowak, Martin
ID - 5449
SN - 2664-1690
TI - Amplification on undirected population structures: Comets beat stars
ER -
TY - GEN
AU - Pavlogiannis, Andreas
AU - Tkadlec, Josef
AU - Chatterjee, Krishnendu
AU - Nowak, Martin
ID - 5451
SN - 2664-1690
TI - Strong amplifiers of natural selection
ER -
TY - GEN
AU - Pavlogiannis, Andreas
AU - Tkadlec, Josef
AU - Chatterjee, Krishnendu
AU - Nowak, Martin
ID - 5452
SN - 2664-1690
TI - Arbitrarily strong amplifiers of natural selection
ER -
TY - GEN
AU - Pavlogiannis, Andreas
AU - Tkadlec, Josef
AU - Chatterjee, Krishnendu
AU - Nowak, Martin
ID - 5453
SN - 2664-1690
TI - Arbitrarily strong amplifiers of natural selection
ER -
TY - DATA
AB - We collected flower colour information on species in the tribe Antirrhineae from taxonomic literature. We also retreived molecular data from GenBank for as many of these species as possible to estimate phylogenetic relationships among these taxa. We then used the R package 'diversitree' to examine patterns of evolutionary transitions between anthocyanin and yellow pigmentation across the phylogeny.
For full details of the methods see:
Ellis TJ and Field DL "Repeated gains in yellow and anthocyanin pigmentation in flower colour transitions in the Antirrhineae”, Annals of Botany (in press)
AU - Ellis, Thomas
AU - Field, David
ID - 5550
TI - Flower colour data and phylogeny (NEXUS) files
ER -
TY - DATA
AB - Data from array experiments investigating pollinator behaviour on snapdragons in controlled conditions, and their effect on plant mating. Data were collected as part of Tom Ellis' PhD thesis , submitted February 2016.
We placed a total of 36 plants in a grid inside a closed organza tent, with a single hive of commercially bred bumblebees (Bombus hortorum). We used only the yellow-flowered Antirrhinum majus striatum and the magenta-flowered Antirrhinum majus pseudomajus, at ratios of 6:36, 12:24, 18:18, 24:12 and 30:6.
After 24 hours to learn how to deal with snapdragons, I observed pollinators foraging on plants, and recorded the transitions between plants. Thereafter seeds on plants were allowed to develops. A sample of these were grown to maturity when their flower colour could be determined, and they were scored as yellow, magenta, or hybrid.
AU - Ellis, Thomas
ID - 5551
TI - Data on pollinator observations and offpsring phenotypes
ER -
TY - DATA
AB - Data on pollinator visitation to wild snapdragons in a natural hybrid zone, collected as part of Tom Ellis' PhD thesis (submitted February 2016).
Snapdragon flowers have a mouth-like structure which pollinators must open to access nectar. We placed 5mm cellophane tags in these mouths, which are held in place by the pressure of the flower until a pollinator visits. When she opens the flower, the tag drops out, and one can infer a visit. We surveyed plants over multiple days in 2010, 2011 and 2012.
Also included are data on phenotypic and demographic variables which may be explanatory variables for pollinator visitation.
AU - Ellis, Thomas
ID - 5552
TI - Pollinator visitation data for wild Antirrhinum majus plants, with phenotypic and frequency data.
ER -
TY - DATA
AB - Genotypic, phenotypic and demographic data for 2128 wild snapdragons and 1127 open-pollinated progeny from a natural hybrid zone, collected as part of Tom Ellis' PhD thesis (submitted) February 2016).
Tissue samples were sent to LGC Genomics in Berlin for DNA extraction, and genotyping at 70 SNP markers by KASPR genotyping. 29 of these SNPs failed to amplify reliably, and have been removed from this dataset.
Other data were retreived from an online database of this population at www.antspec.org.
AU - Field, David
AU - Ellis, Thomas
ID - 5553
KW - paternity assignment
KW - pedigree
KW - matting patterns
KW - assortative mating
KW - Antirrhinum majus
KW - frequency-dependent selection
KW - plant-pollinator interaction
TI - Inference of mating patterns among wild snapdragons in a natural hybrid zone in 2012
ER -
TY - DATA
AB - This FIJI script calculates the population average of the migration speed as a function of time of all cells from wide field microscopy movies.
AU - Hauschild, Robert
ID - 5555
KW - cell migration
KW - wide field microscopy
KW - FIJI
TI - Fiji script to determine average speed and direction of migration of cells
ER -
TY - DATA
AB - MATLAB code and processed datasets available for reproducing the results in:
Lukačišin, M.*, Landon, M.*, Jajoo, R*. (2016) Sequence-Specific Thermodynamic Properties of Nucleic Acids Influence Both Transcriptional Pausing and Backtracking in Yeast.
*equal contributions
AU - Lukacisin, Martin
AU - Landon, Matthieu
AU - Jajoo, Rishi
ID - 5556
KW - transcription
KW - pausing
KW - backtracking
KW - polymerase
KW - RNA
KW - NET-seq
KW - nucleosome
KW - basepairing
TI - MATLAB analysis code for 'Sequence-Specific Thermodynamic Properties of Nucleic Acids Influence Both Transcriptional Pausing and Backtracking in Yeast'
ER -
TY - DATA
AB - Small synthetic discrete tomography problems.
Sizes are 32x32, 64z64 and 256x256.
Projection angles are 2, 4, and 6.
Number of labels are 3 and 5.
AU - Swoboda, Paul
ID - 5557
KW - discrete tomography
TI - Synthetic discrete tomography problems
ER -
TY - DATA
AB - PhD thesis LaTeX source code
AU - Bojsen-Hansen, Morten
ID - 5558
TI - Tracking, Correcting and Absorbing Water Surface Waves
ER -
TY - JOUR
AB - Retroviruses such as HIV-1 assemble and bud from infected cells in an immature, non-infectious form. Subsequently, a series of proteolytic cleavages catalysed by the viral protease leads to a spectacular structural rearrangement of the viral particle into a mature form that is competent to fuse with and infect a new cell. Maturation involves changes in the structures of protein domains, in the interactions between protein domains, and in the architecture of the viral components that are assembled by the proteins. Tight control of proteolytic cleavages at different sites is required for successful maturation, and the process is a major target of antiretroviral drugs. Here we will describe what is known about the structures of immature and mature retrovirus particles, and about the maturation process by which one transitions into the other. Despite a wealth of available data, fundamental questions about retroviral maturation remain unanswered.
AU - Mattei, Simone
AU - Schur, Florian
AU - Briggs, John AG
ID - 5771
IS - 6
JF - Current Opinion in Virology
SN - 1879-6257
TI - Retrovirus maturation—an extraordinary structural transformation
VL - 18
ER -
TY - JOUR
AB - Quantum metrology exploits entangled states of particles to improve sensing precision beyond the limit achievable with uncorrelated particles. All previous methods required detection noise levels below this standard quantum limit to realize the benefits of the intrinsic sensitivity provided by these states.We experimentally demonstrate a widely applicable method for entanglement-enhanced measurements without low-noise detection. The method involves an intermediate quantum phase magnification step that eases implementation complexity. We used it to perform squeezed-state metrology 8 decibels below the standard quantum limit with a detection system that has a noise floor 10 decibels above the standard quantum limit.
AU - Onur Hosten
AU - Krishnakumar, Rajiv
AU - Engelsen, Nils J
AU - Kasevich, Mark A
ID - 587
IS - 6293
JF - Science
TI - Quantum phase magnification
VL - 352
ER -
TY - JOUR
AB - Consider the transmission of a polar code of block length N and rate R over a binary memoryless symmetric channel W and let P e be the block error probability under successive cancellation decoding. In this paper, we develop new bounds that characterize the relationship of the parameters R, N, P e , and the quality of the channel W quantified by its capacity I(W) and its Bhattacharyya parameter Z(W). In previous work, two main regimes were studied. In the error exponent regime, the channel W and the rate R <; I(W) are fixed, and it was proved that the error probability Pe scales roughly as 2 -√N . In the scaling exponent approach, the channel W and the error probability Pe are fixed and it was proved that the gap to capacity I(W) - R scales as N -1/μ . Here, μ is called scaling exponent and this scaling exponent depends on the channel W. A heuristic computation for the binary erasure channel (BEC) gives μ = 3.627 and it was shown that, for any channel W, 3.579 ≤ μ ≤ 5.702. Our contributions are as follows. First, we provide the tighter upper bound μ <;≤ 4.714 valid for any W. With the same technique, we obtain the upper bound μ ≤ 3.639 for the case of the BEC; this upper bound approaches very closely the heuristically derived value for the scaling exponent of the erasure channel. Second, we develop a trade-off between the gap to capacity I(W)- R and the error probability Pe as the functions of the block length N. In other words, we neither fix the gap to capacity (error exponent regime) nor the error probability (scaling exponent regime), but we do consider a moderate deviations regime in which we study how fast both quantities, as the functions of the block length N, simultaneously go to 0. Third, we prove that polar codes are not affected by error floors. To do so, we fix a polar code of block length N and rate R. Then, we vary the channel W and study the impact of this variation on the error probability. We show that the error probability Pe scales as the Bhattacharyya parameter Z(W) raised to a power that scales roughly like VN. This agrees with the scaling in the error exponent regime.
AU - Mondelli, Marco
AU - Hassani, S. Hamed
AU - Urbanke, Rudiger L.
ID - 6732
IS - 12
JF - IEEE Transactions on Information Theory
SN - 0018-9448
TI - Unified scaling of polar codes: Error exponent, scaling exponent, moderate deviations, and error floors
VL - 62
ER -
TY - CONF
AB - The question whether RM codes are capacity-achieving is a long-standing open problem in coding theory that was recently answered in the affirmative for transmission over erasure channels [1], [2]. Remarkably, the proof does not rely on specific properties of RM codes, apart from their symmetry. Indeed, the main technical result consists in showing that any sequence of linear codes, with doubly-transitive permutation groups, achieves capacity on the memoryless erasure channel under bit-MAP decoding. Thus, a natural question is what happens under block-MAP decoding. In [1], [2], by exploiting further symmetries of the code, the bit-MAP threshold was shown to be sharp enough so that the block erasure probability also converges to 0. However, this technique relies heavily on the fact that the transmission is over an erasure channel. We present an alternative approach to strengthen results regarding the bit-MAP threshold to block-MAP thresholds. This approach is based on a careful analysis of the weight distribution of RM codes. In particular, the flavor of the main result is the following: assume that the bit-MAP error probability decays as N -δ , for some δ > 0. Then, the block-MAP error probability also converges to 0. This technique applies to transmission over any binary memoryless symmetric channel. Thus, it can be thought of as a first step in extending the proof that RM codes are capacity-achieving to the general case.
AU - Kudekar, Shrinivas
AU - Kumar, Santhosh
AU - Mondelli, Marco
AU - Pfister, Henry D.
AU - Urbankez, Rudiger
ID - 6733
T2 - 2016 IEEE International Symposium on Information Theory
TI - Comparing the bit-MAP and block-MAP decoding thresholds of Reed-Muller codes on BMS channels
ER -
TY - JOUR
AB - Electrons in materials with linear dispersion behave as massless Weyl- or Dirac-quasiparticles, and continue to intrigue due to their close resemblance to elusive ultra-relativistic particles as well as their potential for future electronics. Yet the experimental signatures of Weyl-fermions are often subtle and indirect, in particular if they coexist with conventional, massive quasiparticles. Here we show a pronounced anomaly in the magnetic torque of the Weyl semimetal NbAs upon entering the quantum limit state in high magnetic fields. The torque changes sign in the quantum limit, signalling a reversal of the magnetic anisotropy that can be directly attributed to the topological nature of the Weyl electrons. Our results establish that anomalous quantum limit torque measurements provide a direct experimental method to identify and distinguish Weyl and Dirac systems.
AU - Moll, Philip J. W.
AU - Potter, Andrew C.
AU - Nair, Nityan L.
AU - Ramshaw, B. J.
AU - Modic, Kimberly A
AU - Riggs, Scott
AU - Zeng, Bin
AU - Ghimire, Nirmal J.
AU - Bauer, Eric D.
AU - Kealhofer, Robert
AU - Ronning, Filip
AU - Analytis, James G.
ID - 7068
JF - Nature Communications
SN - 2041-1723
TI - Magnetic torque anomaly in the quantum limit of Weyl semimetals
VL - 7
ER -
TY - JOUR
AB - A crucial step in the early development of multicellular organisms involves the establishment of spatial patterns of gene expression which later direct proliferating cells to take on different cell fates. These patterns enable the cells to infer their global position within a tissue or an organism by reading out local gene expression levels. The patterning system is thus said to encode positional information, a concept that was formalized recently in the framework of information theory. Here we introduce a toy model of patterning in one spatial dimension, which can be seen as an extension of Wolpert's paradigmatic "French Flag" model, to patterning by several interacting, spatially coupled genes subject to intrinsic and extrinsic noise. Our model, a variant of an Ising spin system, allows us to systematically explore expression patterns that optimally encode positional information. We find that optimal patterning systems use positional cues, as in the French Flag model, together with gene-gene interactions to generate combinatorial codes for position which we call "Counter" patterns. Counter patterns can also be stabilized against noise and variations in system size or morphogen dosage by longer-range spatial interactions of the type invoked in the Turing model. The simple setup proposed here qualitatively captures many of the experimentally observed properties of biological patterning systems and allows them to be studied in a single, theoretically consistent framework.
AU - Hillenbrand, Patrick
AU - Gerland, Ulrich
AU - Tkacik, Gasper
ID - 1270
IS - 9
JF - PLoS One
TI - Beyond the French flag model: Exploiting spatial and gene regulatory interactions for positional information
VL - 11
ER -
TY - JOUR
AB - Background: High directional persistence is often assumed to enhance the efficiency of chemotactic migration. Yet, cells in vivo usually display meandering trajectories with relatively low directional persistence, and the control and function of directional persistence during cell migration in three-dimensional environments are poorly understood. Results: Here, we use mesendoderm progenitors migrating during zebrafish gastrulation as a model system to investigate the control of directional persistence during migration in vivo. We show that progenitor cells alternate persistent run phases with tumble phases that result in cell reorientation. Runs are characterized by the formation of directed actin-rich protrusions and tumbles by enhanced blebbing. Increasing the proportion of actin-rich protrusions or blebs leads to longer or shorter run phases, respectively. Importantly, both reducing and increasing run phases result in larger spatial dispersion of the cells, indicative of reduced migration precision. A physical model quantitatively recapitulating the migratory behavior of mesendoderm progenitors indicates that the ratio of tumbling to run times, and thus the specific degree of directional persistence of migration, are critical for optimizing migration precision. Conclusions: Together, our experiments and model provide mechanistic insight into the control of migration directionality for cells moving in three-dimensional environments that combine different protrusion types, whereby the proportion of blebs to actin-rich protrusions determines the directional persistence and precision of movement by regulating the ratio of tumbling to run times.
AU - Diz Muñoz, Alba
AU - Romanczuk, Pawel
AU - Yu, Weimiao
AU - Bergert, Martin
AU - Ivanovitch, Kenzo
AU - Salbreux, Guillame
AU - Heisenberg, Carl-Philipp J
AU - Paluch, Ewa
ID - 1271
IS - 1
JF - BMC Biology
TI - Steering cell migration by alternating blebs and actin-rich protrusions
VL - 14
ER -
TY - JOUR
AB - We study different means to extend offsetting based on skeletal structures beyond the well-known constant-radius and mitered offsets supported by Voronoi diagrams and straight skeletons, for which the orthogonal distance of offset elements to their respective input elements is constant and uniform over all input elements. Our main contribution is a new geometric structure, called variable-radius Voronoi diagram, which supports the computation of variable-radius offsets, i.e., offsets whose distance to the input is allowed to vary along the input. We discuss properties of this structure and sketch a prototype implementation that supports the computation of variable-radius offsets based on this new variant of Voronoi diagrams.
AU - Held, Martin
AU - Huber, Stefan
AU - Palfrader, Peter
ID - 1272
IS - 5
JF - Computer-Aided Design and Applications
TI - Generalized offsetting of planar structures using skeletons
VL - 13
ER -
TY - JOUR
AB - Lateral root primordia (LRP) originate from pericycle stem cells located deep within parental root tissues. LRP emerge through overlying root tissues by inducing auxin-dependent cell separation and hydraulic changes in adjacent cells. The auxin-inducible auxin influx carrier LAX3 plays a key role concentrating this signal in cells overlying LRP. Delimiting LAX3 expression to two adjacent cell files overlying new LRP is crucial to ensure that auxin-regulated cell separation occurs solely along their shared walls. Multiscale modeling has predicted that this highly focused pattern of expression requires auxin to sequentially induce auxin efflux and influx carriers PIN3 and LAX3, respectively. Consistent with model predictions, we report that auxin-inducible LAX3 expression is regulated indirectly by AUXIN RESPONSE FACTOR 7 (ARF7). Yeast one-hybrid screens revealed that the LAX3 promoter is bound by the transcription factor LBD29, which is a direct target for regulation by ARF7. Disrupting auxin-inducible LBD29 expression or expressing an LBD29-SRDX transcriptional repressor phenocopied the lax3 mutant, resulting in delayed lateral root emergence. We conclude that sequential LBD29 and LAX3 induction by auxin is required to coordinate cell separation and organ emergence.
AU - Porco, Silvana
AU - Larrieu, Antoine
AU - Du, Yujuan
AU - Gaudinier, Allison
AU - Goh, Tatsuaki
AU - Swarup, Kamal
AU - Swarup, Ranjan
AU - Kuempers, Britta
AU - Bishopp, Anthony
AU - Lavenus, Julien
AU - Casimiro, Ilda
AU - Hill, Kristine
AU - Benková, Eva
AU - Fukaki, Hidehiro
AU - Brady, Siobhan
AU - Scheres, Ben
AU - Peéet, Benjamin
AU - Bennett, Malcolm
ID - 1273
IS - 18
JF - Development
TI - Lateral root emergence in Arabidopsis is dependent on transcription factor LBD29 regulation of auxin influx carrier LAX3
VL - 143
ER -
TY - JOUR
AB - Synchronized tissue polarization during regeneration or de novo vascular tissue formation is a plant-specific example of intercellular communication and coordinated development. According to the canalization hypothesis, the plant hormone auxin serves as polarizing signal that mediates directional channel formation underlying the spatio-temporal vasculature patterning. A necessary part of canalization is a positive feedback between auxin signaling and polarity of the intercellular auxin flow. The cellular and molecular mechanisms of this process are still poorly understood, not the least, because of a lack of a suitable model system. We show that the main genetic model plant, Arabidopsis (Arabidopsis thaliana) can be used to study the canalization during vascular cambium regeneration and new vasculature formation. We monitored localized auxin responses, directional auxin-transport channels formation, and establishment of new vascular cambium polarity during regenerative processes after stem wounding. The increased auxin response above and around the wound preceded the formation of PIN1 auxin transporter-marked channels from the primarily homogenous tissue and the transient, gradual changes in PIN1 localization preceded the polarity of newly formed vascular tissue. Thus, Arabidopsis is a useful model for studies of coordinated tissue polarization and vasculature formation after wounding allowing for genetic and mechanistic dissection of the canalization hypothesis.
AU - Mazur, Ewa
AU - Benková, Eva
AU - Friml, Jirí
ID - 1274
JF - Scientific Reports
TI - Vascular cambium regeneration and vessel formation in wounded inflorescence stems of Arabidopsis
VL - 6
ER -
TY - JOUR
AB - The cytochrome (cyt) bc 1 complex is an integral component of the respiratory electron transfer chain sustaining the energy needs of organisms ranging from humans to bacteria. Due to its ubiquitous role in the energy metabolism, both the oxidation and reduction of the enzyme's substrate co-enzyme Q has been studied vigorously. Here, this vast amount of data is reassessed after probing the substrate reduction steps at the Q i-site of the cyt bc 1 complex of Rhodobacter capsulatus using atomistic molecular dynamics simulations. The simulations suggest that the Lys251 side chain could rotate into the Q i-site to facilitate binding of half-protonated semiquinone-a reaction intermediate that is potentially formed during substrate reduction. At this bent pose, the Lys251 forms a salt bridge with the Asp252, thus making direct proton transfer possible. In the neutral state, the lysine side chain stays close to the conserved binding location of cardiolipin (CL). This back-and-forth motion between the CL and Asp252 indicates that Lys251 functions as a proton shuttle controlled by pH-dependent negative feedback. The CL/K/D switching, which represents a refinement to the previously described CL/K pathway, fine-tunes the proton transfer process. Lastly, the simulation data was used to formulate a mechanism for reducing the substrate at the Q i-site.
AU - Postila, Pekka
AU - Kaszuba, Karol
AU - Kuleta, Patryk
AU - Vattulainen, Ilpo
AU - Sarewicz, Marcin
AU - Osyczka, Artur
AU - Róg, Tomasz
ID - 1276
JF - Scientific Reports
TI - Atomistic determinants of co-enzyme Q reduction at the Qi-site of the cytochrome bc1 complex
VL - 6
ER -
TY - JOUR
AB - The Arabidopsis thaliana endogenous elicitor peptides (AtPeps) are released into the apoplast after cellular damage caused by pathogens or wounding to induce innate immunity by direct binding to the membrane-localized leucine-rich repeat receptor kinases, PEP RECEPTOR1 (PEPR1) and PEPR2. Although the PEPR-mediated signaling components and responses have been studied extensively, the contributions of the subcellular localization and dynamics of the active PEPRs remain largely unknown. We used live-cell imaging of the fluorescently labeled and bioactive pep1 to visualize the intracellular behavior of the PEPRs in the Arabidopsis root meristem. We found that AtPep1 decorated the plasma membrane (PM) in a receptor-dependent manner and cointernalized with PEPRs. Trafficking of the AtPep1-PEPR1 complexes to the vacuole required neither the trans-Golgi network/early endosome (TGN/EE)-localized vacuolar H+ -ATPase activity nor the function of the brefeldin A-sensitive ADP-ribosylation factor-guanine exchange factors (ARF-GEFs). In addition, AtPep1 and different TGN/EE markers colocalized only rarely, implying that the intracellular route of this receptor-ligand pair is largely independent of the TGN/EE. Inducible overexpression of the Arabidopsis clathrin coat disassembly factor, Auxilin2, which inhibits clathrin-mediated endocytosis (CME), impaired the AtPep1-PEPR1 internalization and compromised AtPep1-mediated responses. Our results show that clathrin function at the PM is required to induce plant defense responses, likely through CME of cell surface-located signaling components.
AU - Ortiz Morea, Fausto
AU - Savatin, Daniel
AU - Dejonghe, Wim
AU - Kumar, Rahul
AU - Luo, Yu
AU - Adamowski, Maciek
AU - Van Begin, Jos
AU - Dressano, Keini
AU - De Oliveira, Guilherme
AU - Zhao, Xiuyang
AU - Lu, Qing
AU - Madder, Annemieke
AU - Friml, Jirí
AU - De Moura, Daniel
AU - Russinova, Eugenia
ID - 1277
IS - 39
JF - PNAS
TI - Danger-associated peptide signaling in Arabidopsis requires clathrin
VL - 113
ER -
TY - JOUR
AB - Adaptations of vestibulo-ocular and optokinetic response eye movements have been studied as an experimental model of cerebellum-dependent motor learning. Several previous physiological and pharmacological studies have consistently suggested that the cerebellar flocculus (FL) Purkinje cells (P-cells) and the medial vestibular nucleus (MVN) neurons targeted by FL (FL-targeted MVN neurons) may respectively maintain the memory traces of short- and long-term adaptation. To study the basic structures of the FL-MVN synapses by light microscopy (LM) and electron microscopy (EM), we injected green florescence protein (GFP)-expressing lentivirus into FL to anterogradely label the FL P-cell axons in C57BL/6J mice. The FL P-cell axonal boutons were distributed in the magnocellular MVN and in the border region of parvocellular MVN and prepositus hypoglossi (PrH). In the magnocellular MVN, the FL-P cell axons mainly terminated on somata and proximal dendrites. On the other hand, in the parvocellular MVN/PrH, the FL P-cell axonal synaptic boutons mainly terminated on the relatively small-diameter (< 1 μm) distal dendrites of MVN neurons, forming symmetrical synapses. The majority of such parvocellular MVN/PrH neurons were determined to be glutamatergic by immunocytochemistry and in-situ hybridization of GFP expressing transgenic mice. To further examine the spatial relationship between the synapses of FL P-cells and those of vestibular nerve on the neurons of the parvocellular MVN/ PrH, we added injections of biotinylated dextran amine into the semicircular canal and anterogradely labeled vestibular nerve axons in some mice. The MVN dendrites receiving the FL P-cell axonal synaptic boutons often closely apposed vestibular nerve synaptic boutons in both LM and EM studies. Such a partial overlap of synaptic boutons of FL P-cell axons with those of vestibular nerve axons in the distal dendrites of MVN neurons suggests that inhibitory synapses of FL P-cells may influence the function of neighboring excitatory synapses of vestibular nerve in the parvocellular MVN/PrH neurons.
AU - Matsuno, Hitomi
AU - Kudoh, Moeko
AU - Watakabe, Akiya
AU - Yamamori, Tetsuo
AU - Shigemoto, Ryuichi
AU - Nagao, Soichi
ID - 1278
IS - 10
JF - PLoS One
TI - Distribution and structure of synapses on medial vestibular nuclear neurons targeted by cerebellar flocculus purkinje cells and vestibular nerve in mice: Light and electron microscopy studies
VL - 11
ER -
TY - JOUR
AB - During hippocampal sharp wave/ripple (SWR) events, previously occurring, sensory inputdriven neuronal firing patterns are replayed. Such replay is thought to be important for plasticity- related processes and consolidation of memory traces. It has previously been shown that the electrical stimulation-induced disruption of SWR events interferes with learning in rodents in different experimental paradigms. On the other hand, the cognitive map theory posits that the plastic changes of the firing of hippocampal place cells constitute the electrophysiological counterpart of the spatial learning, observable at the behavioral level. Therefore, we tested whether intact SWR events occurring during the sleep/rest session after the first exploration of a novel environment are needed for the stabilization of the CA1 code, which process requires plasticity. We found that the newly-formed representation in the CA1 has the same level of stability with optogenetic SWR blockade as with a control manipulation that delivered the same amount of light into the brain. Therefore our results suggest that at least in the case of passive exploratory behavior, SWR-related plasticity is dispensable for the stability of CA1 ensembles.
AU - Kovács, Krisztián
AU - O'Neill, Joseph
AU - Schönenberger, Philipp
AU - Penttonen, Markku
AU - Rangel Guerrero, Dámaris K
AU - Csicsvari, Jozsef L
ID - 1279
IS - 10
JF - PLoS One
TI - Optogenetically blocking sharp wave ripple events in sleep does not interfere with the formation of stable spatial representation in the CA1 area of the hippocampus
VL - 11
ER -
TY - JOUR
AB - We prove the Wigner-Dyson-Mehta conjecture at fixed energy in the bulk of the spectrum for generalized symmetric and Hermitian Wigner matrices. Previous results concerning the universality of random matrices either require an averaging in the energy parameter or they hold only for Hermitian matrices if the energy parameter is fixed. We develop a homogenization theory of the Dyson Brownian motion and show that microscopic universality follows from mesoscopic statistics.
AU - Bourgade, Paul
AU - Erdös, László
AU - Yau, Horngtzer
AU - Yin, Jun
ID - 1280
IS - 10
JF - Communications on Pure and Applied Mathematics
TI - Fixed energy universality for generalized wigner matrices
VL - 69
ER -
TY - JOUR
AB - Plants are able to modulate root growth and development to optimize their nitrogen nutrition. In Arabidopsis (Arabidopsis thaliana), the adaptive root response to nitrate (NO3 -) depends on the NRT1.1/NPF6.3 transporter/sensor. NRT1.1 represses emergence of lateral root primordia (LRPs) at low concentration or absence of NO3 - through its auxin transport activity that lowers auxin accumulation in LR. However, these functional data strongly contrast with the known transcriptional regulation of NRT1.1, which is markedly repressed in LRPs in the absence of NO3 -. To explain this discrepancy, we investigated in detail the spatiotemporal expression pattern of the NRT1.1 protein during LRP development and combined local transcript analysis with the use of transgenic lines expressing tagged NRT1.1 proteins. Our results show that although NO3 - stimulates NRT1.1 transcription and probably mRNA stability both in primary root tissues and in LRPs, it acts differentially on protein accumulation, depending on the tissues considered with stimulation in cortex and epidermis of the primary root and a strong repression in LRPs and to a lower extent at the primary root tip. This demonstrates that NRT1.1 is strongly regulated at the posttranscriptional level by tissue-specific mechanisms. These mechanisms are crucial for controlling the large palette of adaptive responses to NO3 - mediated by NRT1.1 as they ensure that the protein is present in the proper tissue under the specific conditions where it plays a signaling role in this particular tissue.
AU - Bouguyon, Eléonore
AU - Perrine Walker, Francine
AU - Pervent, Marjorie
AU - Rochette, Juliette
AU - Cuesta, Candela
AU - Benková, Eva
AU - Martinière, Alexandre
AU - Bach, Lien
AU - Krouk, Gabriel
AU - Gojon, Alain
AU - Nacry, Philippe
ID - 1281
IS - 2
JF - Plant Physiology
TI - Nitrate controls root development through posttranscriptional regulation of the NRT1.1/NPF6.3 transporter sensor
VL - 172
ER -
TY - JOUR
AB - We consider higher-dimensional generalizations of the normalized Laplacian and the adjacency matrix of graphs and study their eigenvalues for the Linial–Meshulam model Xk(n, p) of random k-dimensional simplicial complexes on n vertices. We show that for p = Ω(logn/n), the eigenvalues of each of the matrices are a.a.s. concentrated around two values. The main tool, which goes back to the work of Garland, are arguments that relate the eigenvalues of these matrices to those of graphs that arise as links of (k - 2)-dimensional faces. Garland’s result concerns the Laplacian; we develop an analogous result for the adjacency matrix. The same arguments apply to other models of random complexes which allow for dependencies between the choices of k-dimensional simplices. In the second part of the paper, we apply this to the question of possible higher-dimensional analogues of the discrete Cheeger inequality, which in the classical case of graphs relates the eigenvalues of a graph and its edge expansion. It is very natural to ask whether this generalizes to higher dimensions and, in particular, whether the eigenvalues of the higher-dimensional Laplacian capture the notion of coboundary expansion—a higher-dimensional generalization of edge expansion that arose in recent work of Linial and Meshulam and of Gromov; this question was raised, for instance, by Dotterrer and Kahle. We show that this most straightforward version of a higher-dimensional discrete Cheeger inequality fails, in quite a strong way: For every k ≥ 2 and n ∈ N, there is a k-dimensional complex Yn k on n vertices that has strong spectral expansion properties (all nontrivial eigenvalues of the normalised k-dimensional Laplacian lie in the interval [1−O(1/√1), 1+0(1/√1]) but whose coboundary expansion is bounded from above by O(log n/n) and so tends to zero as n → ∞; moreover, Yn k can be taken to have vanishing integer homology in dimension less than k.
AU - Gundert, Anna
AU - Wagner, Uli
ID - 1282
IS - 2
JF - Israel Journal of Mathematics
TI - On eigenvalues of random complexes
VL - 216
ER -