TY - GEN
AB - As a consequence of its difference in copy number between males and females, the X chromosome is subject to unique evolutionary forces and gene regulatory mechanisms. Previous studies of Drosophila melanogaster have shown that the expression of X-linked, testis-specific reporter genes is suppressed in the male germline. However, it is not known whether this phenomenon is restricted to testis-expressed genes or if it is a more general property of genes with tissue-specific expression, which are also underrepresented on the X chromosome. To test this, we compared the expression of three tissue-specific reporter genes (ovary, accessory gland and Malpighian tubule) inserted at various autosomal and X-chromosomal locations. In contrast to testis-specific reporter genes, we found no reduction of X-linked expression in any of the other tissues. In accessory gland and Malpighian tubule, we detected higher expression of the X-linked reporter genes, which suggests that they are at least partially dosage compensated. We found no difference in the tissue-specificity of X-linked and autosomal reporter genes. These findings indicate that, in general, the X chromosome is not a detrimental environment for tissue-specific gene expression and that the suppression of X-linked expression is limited to the male germline.
AU - Argyridou, Eliza
AU - Huylmans, Ann K
AU - Königer, Annabella
AU - Parsch, John
ID - 9861
TI - Data from: X-linkage is not a general inhibitor of tissue-specific gene expression in Drosophila melanogaster
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 - CONF
AB - We present a generalized optimal transport model in which the mass-preserving constraint for the L2-Wasserstein distance is relaxed by introducing a source term in the continuity equation. The source term is also incorporated in the path energy by means of its squared L2-norm in time of a functional with linear growth in space. This extension of the original transport model enables local density modulations, which is a desirable feature in applications such as image warping and blending. A key advantage of the use of a functional with linear growth in space is that it allows for singular sources and sinks, which can be supported on points or lines. On a technical level, the L2-norm in time ensures a disintegration of the source in time, which we use to obtain the well-posedness of the model and the existence of geodesic paths. The numerical discretization is based on the proximal splitting approach [18] and selected numerical test cases show the potential of the proposed approach. Furthermore, the approach is applied to the warping and blending of textures.
AU - Maas, Jan
AU - Rumpf, Martin
AU - Simon, Stefan
ED - Lauze, François
ED - Dong, Yiqiu
ED - Bjorholm Dahl, Anders
ID - 989
SN - 03029743
TI - Transport based image morphing with intensity modulation
VL - 10302
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 - JOUR
AB - Synaptotagmin 7 (Syt7) was originally identified as a slow Ca2+ sensor for lysosome fusion, but its function at fast synapses is controversial. The paper by Luo and Südhof (2017) in this issue of Neuron shows that at the calyx of Held in the auditory brainstem Syt7 triggers asynchronous release during stimulus trains, resulting in reliable and temporally precise high-frequency transmission. Thus, a slow Ca2+ sensor contributes to the fast signaling properties of the calyx synapse.
AU - Chen, Chong
AU - Jonas, Peter M
ID - 991
IS - 4
JF - Neuron
SN - 08966273
TI - Synaptotagmins: That’s why so many
VL - 94
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 - 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 - 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 - We introduce planar matchings on directed pseudo-line arrangements, which yield a planar set of pseudo-line segments such that only matching-partners are adjacent. By translating the planar matching problem into a corresponding stable roommates problem we show that such matchings always exist. Using our new framework, we establish, for the first time, a complete, rigorous definition of weighted straight skeletons, which are based on a so-called wavefront propagation process. We present a generalized and unified approach to treat structural changes in the wavefront that focuses on the restoration of weak planarity by finding planar matchings.
AU - Biedl, Therese
AU - Huber, Stefan
AU - Palfrader, Peter
ID - 481
IS - 3-4
JF - International Journal of Computational Geometry and Applications
TI - Planar matchings for weighted straight skeletons
VL - 26
ER -
TY - JOUR
AB - Two-player games on graphs provide the theoretical framework for many important problems such as reactive synthesis. While the traditional study of two-player zero-sum games has been extended to multi-player games with several notions of equilibria, they are decidable only for perfect-information games, whereas several applications require imperfect-information. In this paper we propose a new notion of equilibria, called doomsday equilibria, which is a strategy profile where all players satisfy their own objective, and if any coalition of players deviates and violates even one of the players' objective, then the objective of every player is violated. We present algorithms and complexity results for deciding the existence of doomsday equilibria for various classes of ω-regular objectives, both for imperfect-information games, and for perfect-information games. We provide optimal complexity bounds for imperfect-information games, and in most cases for perfect-information games.
AU - Chatterjee, Krishnendu
AU - Doyen, Laurent
AU - Filiot, Emmanuel
AU - Raskin, Jean
ID - 681
JF - Information and Computation
SN - 08905401
TI - Doomsday equilibria for omega-regular games
VL - 254
ER -
TY - JOUR
AB - Auxin steers numerous physiological processes in plants, making the tight control of its endogenous levels and spatiotemporal distribution a necessity. This regulation is achieved by different mechanisms, including auxin biosynthesis, metabolic conversions, degradation, and transport. Here, we introduce cis-cinnamic acid (c-CA) as a novel and unique addition to a small group of endogenous molecules affecting in planta auxin concentrations. c-CA is the photo-isomerization product of the phenylpropanoid pathway intermediate trans-CA (t-CA). When grown on c-CA-containing medium, an evolutionary diverse set of plant species were shown to exhibit phenotypes characteristic for high auxin levels, including inhibition of primary root growth, induction of root hairs, and promotion of adventitious and lateral rooting. By molecular docking and receptor binding assays, we showed that c-CA itself is neither an auxin nor an anti-auxin, and auxin profiling data revealed that c-CA does not significantly interfere with auxin biosynthesis. Single cell-based auxin accumulation assays showed that c-CA, and not t-CA, is a potent inhibitor of auxin efflux. Auxin signaling reporters detected changes in spatiotemporal distribution of the auxin response along the root of c-CA-treated plants, and long-distance auxin transport assays showed no inhibition of rootward auxin transport. Overall, these results suggest that the phenotypes of c-CA-treated plants are the consequence of a local change in auxin accumulation, induced by the inhibition of auxin efflux. This work reveals a novel mechanism how plants may regulate auxin levels and adds a novel, naturally occurring molecule to the chemical toolbox for the studies of auxin homeostasis.
AU - Steenackers, Ward
AU - Klíma, Petr
AU - Quareshy, Mussa
AU - Cesarino, Igor
AU - Kumpf, Robert
AU - Corneillie, Sander
AU - Araújo, Pedro
AU - Viaene, Tom
AU - Goeminne, Geert
AU - Nowack, Moritz
AU - Ljung, Karin
AU - Friml, Jirí
AU - Blakeslee, Joshua
AU - Novák, Ondřej
AU - Zažímalová, Eva
AU - Napier, Richard
AU - Boerjan, Wout
AU - Vanholme, Bartel
ID - 1159
IS - 1
JF - Plant Physiology
SN - 0032-0889
TI - Cis-cinnamic acid is a novel natural auxin efflux inhibitor that promotes lateral root formation
VL - 173
ER -
TY - CHAP
AB - In the analysis of reactive systems a quantitative objective assigns a real value to every trace of the system. The value decision problem for a quantitative objective requires a trace whose value is at least a given threshold, and the exact value decision problem requires a trace whose value is exactly the threshold. We compare the computational complexity of the value and exact value decision problems for classical quantitative objectives, such as sum, discounted sum, energy, and mean-payoff for two standard models of reactive systems, namely, graphs and graph games.
AU - Chatterjee, Krishnendu
AU - Doyen, Laurent
AU - Henzinger, Thomas A
ED - Aceto, Luca
ED - Bacci, Giorgio
ED - Ingólfsdóttir, Anna
ED - Legay, Axel
ED - Mardare, Radu
ID - 625
SN - 0302-9743
T2 - Models, Algorithms, Logics and Tools
TI - The cost of exactness in quantitative reachability
VL - 10460
ER -
TY - BOOK
AB - This book is a concise and self-contained introduction of recent techniques to prove local spectral universality for large random matrices. Random matrix theory is a fast expanding research area, and this book mainly focuses on the methods that the authors participated in developing over the past few years. Many other interesting topics are not included, and neither are several new developments within the framework of these methods. The authors have chosen instead to present key concepts that they believe are the core of these methods and should be relevant for future applications. They keep technicalities to a minimum to make the book accessible to graduate students. With this in mind, they include in this book the basic notions and tools for high-dimensional analysis, such as large deviation, entropy, Dirichlet form, and the logarithmic Sobolev inequality.
AU - Erdös, László
AU - Yau, Horng
ID - 567
SN - 9-781-4704-3648-3
TI - A Dynamical Approach to Random Matrix Theory
VL - 28
ER -
TY - CHAP
AB - We give a short overview on a recently developed notion of Ricci curvature for discrete spaces. This notion relies on geodesic convexity properties of the relative entropy along geodesics in the space of probability densities, for a metric which is similar to (but different from) the 2-Wasserstein metric. The theory can be considered as a discrete counterpart to the theory of Ricci curvature for geodesic measure spaces developed by Lott–Sturm–Villani.
AU - Maas, Jan
ED - Najman, Laurent
ED - Romon, Pascal
ID - 649
SN - 978-3-319-58001-2
T2 - Modern Approaches to Discrete Curvature
TI - Entropic Ricci curvature for discrete spaces
VL - 2184
ER -
TY - GEN
AB - This book constitutes the refereed proceedings of the 9th InternationalWorkshop on Numerical Software Verification, NSV 2016, held in Toronto, ON, Canada in July 2011 - colocated with CAV 2016, the 28th International Conference on Computer Aided Verification.
The NSV workshop is dedicated to the development of logical and mathematical techniques for the reasoning about programmability and reliability.
ED - Bogomolov, Sergiy
ED - Martel, Matthieu
ED - Prabhakar, Pavithra
ID - 638
SN - 0302-9743
TI - Numerical Software Verification
VL - 10152
ER -
TY - JOUR
AB - We consider N×N Hermitian random matrices H consisting of blocks of size M≥N6/7. The matrix elements are i.i.d. within the blocks, close to a Gaussian in the four moment matching sense, but their distribution varies from block to block to form a block-band structure, with an essential band width M. We show that the entries of the Green’s function G(z)=(H−z)−1 satisfy the local semicircle law with spectral parameter z=E+iη down to the real axis for any η≫N−1, using a combination of the supersymmetry method inspired by Shcherbina (J Stat Phys 155(3): 466–499, 2014) and the Green’s function comparison strategy. Previous estimates were valid only for η≫M−1. The new estimate also implies that the eigenvectors in the middle of the spectrum are fully delocalized.
AU - Bao, Zhigang
AU - Erdös, László
ID - 1528
IS - 3-4
JF - Probability Theory and Related Fields
SN - 01788051
TI - Delocalization for a class of random block band matrices
VL - 167
ER -
TY - THES
AB - Restriction-modification (RM) represents the simplest and possibly the most widespread mechanism of self/non-self discrimination in nature. In order to provide bacteria with immunity against bacteriophages and other parasitic genetic elements, RM systems rely on a balance between two enzymes: the restriction enzyme, which cleaves non-self DNA at specific restriction sites, and the modification enzyme, which tags the host’s DNA as self and thus protects it from cleavage. In this thesis, I use population and single-cell level experiments in combination with mathematical modeling to study different aspects of the interplay between RM systems, bacteria and bacteriophages. First, I analyze how mutations in phage restriction sites affect the probability of phage escape – an inherently stochastic process, during which phages accidently get modified instead of restricted. Next, I use single-cell experiments to show that RM systems can, with a low probability, attack the genome of their bacterial host and that this primitive form of autoimmunity leads to a tradeoff between the evolutionary cost and benefit of RM systems. Finally, I investigate the nature of interactions between bacteria, RM systems and temperate bacteriophages to find that, as a consequence of phage escape and its impact on population dynamics, RM systems can promote acquisition of symbiotic bacteriophages, rather than limit it. The results presented here uncover new fundamental biological properties of RM systems and highlight their importance in the ecology and evolution of bacteria, bacteriophages and their interactions.
AU - Pleska, Maros
ID - 202
TI - Biology of restriction-modification systems at the single-cell and population level
ER -
TY - JOUR
AB - Restriction–modification systems are widespread genetic elements that protect bacteria from bacteriophage infections by recognizing and cleaving heterologous DNA at short, well-defined sequences called restriction sites. Bioinformatic evidence shows that restriction sites are significantly underrepresented in bacteriophage genomes, presumably because bacteriophages with fewer restriction sites are more likely to escape cleavage by restriction–modification systems. However, how mutations in restriction sites affect the likelihood of bacteriophage escape is unknown. Using the bacteriophage l and the restriction–modification system EcoRI, we show that while mutation effects at different restriction sites are unequal, they are independent. As a result, the probability of bacteriophage escape increases with each mutated restriction site. Our results experimentally support the role of restriction site avoidance as a response to selection imposed by restriction–modification systems and offer an insight into the events underlying the process of bacteriophage escape.
AU - Pleska, Maros
AU - Guet, Calin C
ID - 561
IS - 12
JF - Biology Letters
SN - 1744-9561
TI - Effects of mutations in phage restriction sites during escape from restriction–modification
VL - 13
ER -
TY - JOUR
AB - From microwave ovens to satellite television to the GPS and data services on our mobile phones, microwave technology is everywhere today. But one technology that has so far failed to prove its worth in this wavelength regime is quantum communication that uses the states of single photons as information carriers. This is because single microwave photons, as opposed to classical microwave signals, are extremely vulnerable to noise from thermal excitations in the channels through which they travel. Two new independent studies, one by Ze-Liang Xiang at Technische Universität Wien (Vienna), Austria, and colleagues [1] and another by Benoît Vermersch at the University of Innsbruck, also in Austria, and colleagues [2] now describe a theoretical protocol for microwave quantum communication that is resilient to thermal and other types of noise. Their approach could become a powerful technique to establish fast links between superconducting data processors in a future all-microwave quantum network.
AU - Fink, Johannes M
ID - 1013
IS - 32
JF - Physics
TI - Viewpoint: Microwave quantum states beat the heat
VL - 10
ER -
TY - GEN
AB - information on culture conditions, phage mutagenesis, verification and lysate preparation; Raw data
AU - Pleska, Maros
AU - Guet, Calin C
ID - 9847
TI - Supplementary materials and methods; Full data set from effects of mutations in phage restriction sites during escape from restriction–modification
ER -
TY - JOUR
AB - The extent of heterogeneity among driver gene mutations present in naturally occurring metastases - that is, treatment-naive metastatic disease - is largely unknown. To address this issue, we carried out 60× whole-genome sequencing of 26 metastases from four patients with pancreatic cancer. We found that identical mutations in known driver genes were present in every metastatic lesion for each patient studied. Passenger gene mutations, which do not have known or predicted functional consequences, accounted for all intratumoral heterogeneity. Even with respect to these passenger mutations, our analysis suggests that the genetic similarity among the founding cells of metastases was higher than that expected for any two cells randomly taken from a normal tissue. The uniformity of known driver gene mutations among metastases in the same patient has critical and encouraging implications for the success of future targeted therapies in advanced-stage disease.
AU - Makohon Moore, Alvin
AU - Zhang, Ming
AU - Reiter, Johannes
AU - Božić, Ivana
AU - Allen, Benjamin
AU - Kundu, Deepanjan
AU - Chatterjee, Krishnendu
AU - Wong, Fay
AU - Jiao, Yuchen
AU - Kohutek, Zachary
AU - Hong, Jungeui
AU - Attiyeh, Marc
AU - Javier, Breanna
AU - Wood, Laura
AU - Hruban, Ralph
AU - Nowak, Martin
AU - Papadopoulos, Nickolas
AU - Kinzler, Kenneth
AU - Vogelstein, Bert
AU - Iacobuzio Donahue, Christine
ID - 653
IS - 3
JF - Nature Genetics
SN - 10614036
TI - Limited heterogeneity of known driver gene mutations among the metastases of individual patients with pancreatic cancer
VL - 49
ER -
TY - JOUR
AB - Since 2006, reprogrammed cells have increasingly been used as a biomedical research technique in addition to neuro-psychiatric methods. These rapidly evolving techniques allow for the generation of neuronal sub-populations, and have sparked interest not only in monogenetic neuro-psychiatric diseases, but also in poly-genetic and poly-aetiological disorders such as schizophrenia (SCZ) and bipolar disorder (BPD). This review provides a summary of 19 publications on reprogrammed adult somatic cells derived from patients with SCZ, and five publications using this technique in patients with BPD. As both disorders are complex and heterogeneous, there is a plurality of hypotheses to be tested in vitro. In SCZ, data on alterations of dopaminergic transmission in vitro are sparse, despite the great explanatory power of the so-called DA hypothesis of SCZ. Some findings correspond to perturbations of cell energy metabolism, and observations in reprogrammed cells suggest neuro-developmental alterations. Some studies also report on the efficacy of medicinal compounds to revert alterations observed in cellular models. However, due to the paucity of replication studies, no comprehensive conclusions can be drawn from studies using reprogrammed cells at the present time. In the future, findings from cell culture methods need to be integrated with clinical, epidemiological, pharmacological and imaging data in order to generate a more comprehensive picture of SCZ and BPD.
AU - Sauerzopf, Ulrich
AU - Sacco, Roberto
AU - Novarino, Gaia
AU - Niello, Marco
AU - Weidenauer, Ana
AU - Praschak Rieder, Nicole
AU - Sitte, Harald
AU - Willeit, Matthaeus
ID - 1228
IS - 1
JF - European Journal of Neuroscience
TI - Are reprogrammed cells a useful tool for studying dopamine dysfunction in psychotic disorders? A review of the current evidence
VL - 45
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 - JOUR
AB - The optogenetic revolution enabled spatially-precise and temporally-precise control over protein function, signaling pathway activation, and animal behavior with tremendous success in the dissection of signaling networks and neural circuits. Very recently, optogenetic methods have been paired with optical reporters in novel drug screening platforms. In these all-optical platforms, light remotely activated ion channels and kinases thereby obviating the use of electrophysiology or reagents. Consequences were remarkable operational simplicity, throughput, and cost-effectiveness that culminated in the identification of new drug candidates. These blueprints for all-optical assays also revealed potential pitfalls and inspire all-optical variants of other screens, such as those that aim at better understanding dynamic drug action or orphan protein function.
AU - Agus, Viviana
AU - Janovjak, Harald L
ID - 1026
JF - Current Opinion in Biotechnology
SN - 09581669
TI - Optogenetic methods in drug screening: Technologies and applications
VL - 48
ER -
TY - JOUR
AB - Phat is an open-source C. ++ library for the computation of persistent homology by matrix reduction, targeted towards developers of software for topological data analysis. We aim for a simple generic design that decouples algorithms from data structures without sacrificing efficiency or user-friendliness. We provide numerous different reduction strategies as well as data types to store and manipulate the boundary matrix. We compare the different combinations through extensive experimental evaluation and identify optimization techniques that work well in practical situations. We also compare our software with various other publicly available libraries for persistent homology.
AU - Bauer, Ulrich
AU - Kerber, Michael
AU - Reininghaus, Jan
AU - Wagner, Hubert
ID - 1433
JF - Journal of Symbolic Computation
SN - 07477171
TI - Phat - Persistent homology algorithms toolbox
VL - 78
ER -
TY - JOUR
AB - Heavy holes confined in quantum dots are predicted to be promising candidates for the realization of spin qubits with long coherence times. Here we focus on such heavy-hole states confined in germanium hut wires. By tuning the growth density of the latter we can realize a T-like structure between two neighboring wires. Such a structure allows the realization of a charge sensor, which is electrostatically and tunnel coupled to a quantum dot, with charge-transfer signals as high as 0.3 e. By integrating the T-like structure into a radiofrequency reflectometry setup, single-shot measurements allowing the extraction of hole tunneling times are performed. The extracted tunneling times of less than 10 μs are attributed to the small effective mass of Ge heavy-hole states and pave the way toward projective spin readout measurements.
AU - Vukusic, Lada
AU - Kukucka, Josip
AU - Watzinger, Hannes
AU - Katsaros, Georgios
ID - 840
IS - 9
JF - Nano Letters
SN - 15306984
TI - Fast hole tunneling times in germanium hut wires probed by single-shot reflectometry
VL - 17
ER -
TY - CONF
AB - Graph games provide the foundation for modeling and synthesis of reactive processes. Such games are played over graphs where the vertices are controlled by two adversarial players. We consider graph games where the objective of the first player is the conjunction of a qualitative objective (specified as a parity condition) and a quantitative objective (specified as a meanpayoff condition). There are two variants of the problem, namely, the threshold problem where the quantitative goal is to ensure that the mean-payoff value is above a threshold, and the value problem where the quantitative goal is to ensure the optimal mean-payoff value; in both cases ensuring the qualitative parity objective. The previous best-known algorithms for game graphs with n vertices, m edges, parity objectives with d priorities, and maximal absolute reward value W for mean-payoff objectives, are as follows: O(nd+1 . m . w) for the threshold problem, and O(nd+2 · m · W) for the value problem. Our main contributions are faster algorithms, and the running times of our algorithms are as follows: O(nd-1 · m ·W) for the threshold problem, and O(nd · m · W · log(n · W)) for the value problem. For mean-payoff parity objectives with two priorities, our algorithms match the best-known bounds of the algorithms for mean-payoff games (without conjunction with parity objectives). Our results are relevant in synthesis of reactive systems with both functional requirement (given as a qualitative objective) and performance requirement (given as a quantitative objective).
AU - Chatterjee, Krishnendu
AU - Henzinger, Monika H
AU - Svozil, Alexander
ID - 552
SN - 978-395977046-0
T2 - Leibniz International Proceedings in Informatics
TI - Faster algorithms for mean-payoff parity games
VL - 83
ER -
TY - CONF
AB - Graph games with omega-regular winning conditions provide a mathematical framework to analyze a wide range of problems in the analysis of reactive systems and programs (such as the synthesis of reactive systems, program repair, and the verification of branching time properties). Parity conditions are canonical forms to specify omega-regular winning conditions. Graph games with parity conditions are equivalent to mu-calculus model checking, and thus a very important algorithmic problem. Symbolic algorithms are of great significance because they provide scalable algorithms for the analysis of large finite-state systems, as well as algorithms for the analysis of infinite-state systems with finite quotient. A set-based symbolic algorithm uses the basic set operations and the one-step predecessor operators. We consider graph games with n vertices and parity conditions with c priorities (equivalently, a mu-calculus formula with c alternations of least and greatest fixed points). While many explicit algorithms exist for graph games with parity conditions, for set-based symbolic algorithms there are only two algorithms (notice that we use space to refer to the number of sets stored by a symbolic algorithm): (a) the basic algorithm that requires O(n^c) symbolic operations and linear space; and (b) an improved algorithm that requires O(n^{c/2+1}) symbolic operations but also O(n^{c/2+1}) space (i.e., exponential space). In this work we present two set-based symbolic algorithms for parity games: (a) our first algorithm requires O(n^{c/2+1}) symbolic operations and only requires linear space; and (b) developing on our first algorithm, we present an algorithm that requires O(n^{c/3+1}) symbolic operations and only linear space. We also present the first linear space set-based symbolic algorithm for parity games that requires at most a sub-exponential number of symbolic operations.
AU - Chatterjee, Krishnendu
AU - Dvorák, Wolfgang
AU - Henzinger, Monika H
AU - Loitzenbauer, Veronika
ID - 6519
TI - Improved set-based symbolic algorithms for parity games
VL - 82
ER -
TY - JOUR
AB - The computation of the winning set for parity objectives and for Streett objectives in graphs as well as in game graphs are central problems in computer-aided verification, with application to the verification of closed systems with strong fairness conditions, the verification of open systems, checking interface compatibility, well-formedness of specifications, and the synthesis of reactive systems. We show how to compute the winning set on n vertices for (1) parity-3 (aka one-pair Streett) objectives in game graphs in time O(n5/2) and for (2) k-pair Streett objectives in graphs in time O(n2+nklogn). For both problems this gives faster algorithms for dense graphs and represents the first improvement in asymptotic running time in 15 years.
AU - Chatterjee, Krishnendu
AU - Henzinger, Monika H
AU - Loitzenbauer, Veronika
ID - 464
IS - 3
JF - Logical Methods in Computer Science
SN - 18605974
TI - Improved algorithms for parity and Streett objectives
VL - 13
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 - Immune cells communicate using cytokine signals, but the quantitative rules of this communication aren't clear. In this issue of Immunity, Oyler-Yaniv et al. (2017) suggest that the distribution of a cytokine within a lymphatic organ is primarily governed by the local density of cells consuming it.
AU - Assen, Frank P
AU - Sixt, Michael K
ID - 664
IS - 4
JF - Immunity
SN - 10747613
TI - The dynamic cytokine niche
VL - 46
ER -
TY - JOUR
AB - Cell-cell contact formation constitutes an essential step in evolution, leading to the differentiation of specialized cell types. However, remarkably little is known about whether and how the interplay between contact formation and fate specification affects 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 ppl cell-fate specification. We further show that Nodal signaling promotes ppl cell-cell contact duration, generating a positive feedback loop between ppl cell-cell contact duration and cell-fate specification. Finally, by combining mathematical modeling and experimentation, we show that this feedback determines whether anterior axial mesendoderm cells become ppl or, instead, turn into endoderm. Thus, the interdependent activities of cell-cell signaling and contact formation control fate diversification within the developing embryo.
AU - Barone, Vanessa
AU - Lang, Moritz
AU - Krens, Gabriel
AU - Pradhan, Saurabh
AU - Shamipour, Shayan
AU - Sako, Keisuke
AU - Sikora, Mateusz K
AU - Guet, Calin C
AU - Heisenberg, Carl-Philipp J
ID - 735
IS - 2
JF - Developmental Cell
SN - 15345807
TI - An effective feedback loop between cell-cell contact duration and morphogen signaling determines cell fate
VL - 43
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 - Optogenetics and photopharmacology provide spatiotemporally precise control over protein interactions and protein function in cells and animals. Optogenetic methods that are sensitive to green light and can be used to break protein complexes are not broadly available but would enable multichromatic experiments with previously inaccessible biological targets. Herein, we repurposed cobalamin (vitamin B12) binding domains of bacterial CarH transcription factors for green-light-induced receptor dissociation. In cultured cells, we observed oligomerization-induced cell signaling for the fibroblast growth factor receptor 1 fused to cobalamin-binding domains in the dark that was rapidly eliminated upon illumination. In zebrafish embryos expressing fusion receptors, green light endowed control over aberrant fibroblast growth factor signaling during development. Green-light-induced domain dissociation and light-inactivated receptors will critically expand the optogenetic toolbox for control of biological processes.
AU - Kainrath, Stephanie
AU - Stadler, Manuela
AU - Gschaider-Reichhart, Eva
AU - Distel, Martin
AU - Janovjak, Harald L
ID - 1028
IS - 16
JF - Angewandte Chemie - International Edition
SN - 14337851
TI - Green-light-induced inactivation of receptor signaling using cobalamin-binding domains
VL - 56
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 - 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 - 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 - 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 - 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 - 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 - 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 - Clinical guidelines and decision support systems (DSS) play an important role in daily practices of medicine. Many text-based guidelines have been encoded for work-flow simulation of DSS to automate health care. During the collaboration with Carle hospital to develop a DSS, we identify that, for some complex and life-critical diseases, it is highly desirable to automatically rigorously verify some complex temporal properties in guidelines, which brings new challenges to current simulation based DSS with limited support of automatical formal verification and real-time data analysis. In this paper, we conduct the first study on applying runtime verification to cooperate with current DSS based on real-time data. Within the proposed technique, a user-friendly domain specific language, named DRTV, is designed to specify vital real-time data sampled by medical devices and temporal properties originated from clinical guidelines. Some interfaces are developed for data acquisition and communication. Then, for medical practice scenarios described in DRTV model, we will automatically generate event sequences and runtime property verifier automata. If a temporal property violates, real-time warnings will be produced by the formal verifier and passed to medical DSS. We have used DRTV to specify different kinds of medical care scenarios, and applied the proposed technique to assist existing DSS. As presented in experiment results, in terms of warning detection, it outperforms the only use of DSS or human inspection, and improves the quality of clinical health care of hospital
AU - Jiang, Yu
AU - Liu, Han
AU - Kong, Hui
AU - Wang, Rui
AU - Hosseini, Mohamad
AU - Sun, Jiaguang
AU - Sha, Lui
ID - 479
T2 - Proceedings of the 38th International Conference on Software Engineering Companion
TI - Use runtime verification to improve the quality of medical care practice
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 - CONF
AB - Nonlinear electro-optical conversion of microwave radiation into the optical telecommunication band is achieved within a crystalline whispering gallery mode resonator, reaching 0.1% photon number conversion efficiency with MHz bandwidth.
AU - Rueda, Alfredo
AU - Sedlmeir, Florian
AU - Collodo, Michele
AU - Vogl, Ulrich
AU - Stiller, Birgit
AU - Schunk, Gerhard
AU - Strekalov, Dmitry
AU - Marquardt, Christoph
AU - Fink, Johannes M
AU - Painter, Oskar
AU - Leuchs, Gerd
AU - Schwefel, Harald
ID - 482
TI - Nonlinear single sideband microwave to optical conversion using an electro-optic WGM-resonator
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 - The data stored here is used in Murat Tugrul's PhD thesis (Chapter 3), which is related to the evolution of bacterial RNA polymerase binding.
Magdalena Steinrueck (PhD Student in Calin Guet's group at IST Austria) performed the experiments and created the data on de novo promoter evolution. Fabienne Jesse (PhD Student in Jon Bollback's group at IST Austria) performed the experiments and created the data on lac promoter evolution.
AU - Tugrul, Murat
ID - 5554
KW - RNAP binding
KW - de novo promoter evolution
KW - lac promoter
TI - Experimental Data for Binding Site Evolution of Bacterial RNA Polymerase
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 - Parasitism creates selection for resistance mechanisms in host populations and is hypothesized to promote increased host evolvability. However, the influence of these traits on host evolution when parasites are no longer present is unclear. We used experimental evolution and whole-genome sequencing of Escherichia coli to determine the effects of past and present exposure to parasitic viruses (phages) on the spread of mutator alleles, resistance, and bacterial competitive fitness. We found that mutator alleles spread rapidly during adaptation to any of four different phage species, and this pattern was even more pronounced with multiple phages present simultaneously. However, hypermutability did not detectably accelerate adaptation in the absence of phages and recovery of fitness costs associated with resistance. Several lineages evolved phage resistance through elevated mucoidy, and during subsequent evolution in phage-free conditions they rapidly reverted to nonmucoid, phage-susceptible phenotypes. Genome sequencing revealed that this phenotypic reversion was achieved by additional genetic changes rather than by genotypic reversion of the initial resistance mutations. Insertion sequence (IS) elements played a key role in both the acquisition of resistance and adaptation in the absence of parasites; unlike single nucleotide polymorphisms, IS insertions were not more frequent in mutator lineages. Our results provide a genetic explanation for rapid reversion of mucoidy, a phenotype observed in other bacterial species including human pathogens. Moreover, this demonstrates that the types of genetic change underlying adaptation to fitness costs, and consequently the impact of evolvability mechanisms such as increased point-mutation rates, depend critically on the mechanism of resistance.
AU - Wielgoss, Sébastien
AU - Bergmiller, Tobias
AU - Bischofberger, Anna M.
AU - Hall, Alex R.
ID - 5749
IS - 3
JF - Molecular Biology and Evolution
SN - 0737-4038
TI - Adaptation to parasites and costs of parasite resistance in mutator and nonmutator bacteria
VL - 33
ER -
TY - CONF
AB - The Continuous Skolem Problem asks whether a real-valued function satisfying a linear differen-
tial equation has a zero in a given interval of real numbers. This is a fundamental reachability
problem for continuous linear dynamical systems, such as linear hybrid automata and continuous-
time Markov chains. Decidability of the problem is currently open – indeed decidability is open
even for the sub-problem in which a zero is sought in a bounded interval. In this paper we show
decidability of the bounded problem subject to Schanuel’s Conjecture, a unifying conjecture in
transcendental number theory. We furthermore analyse the unbounded problem in terms of the
frequencies of the differential equation, that is, the imaginary parts of the characteristic roots.
We show that the unbounded problem can be reduced to the bounded problem if there is at most
one rationally linearly independent frequency, or if there are two rationally linearly independent
frequencies and all characteristic roots are simple. We complete the picture by showing that de-
cidability of the unbounded problem in the case of two (or more) rationally linearly independent
frequencies would entail a major new effectiveness result in Diophantine approximation, namely
computability of the Diophantine-approximation types of all real algebraic numbers.
AU - Chonev, Ventsislav K
AU - Ouaknine, Joël
AU - Worrell, James
ID - 1069
TI - On the skolem problem for continuous linear dynamical systems
VL - 55
ER -
TY - CONF
AB - We present a logic that extends CTL (Computation Tree Logic) with operators that express synchronization properties. A property is synchronized in a system if it holds in all paths of a certain length. The new logic is obtained by using the same path quantifiers and temporal operators as in CTL, but allowing a different order of the quantifiers. This small syntactic variation induces a logic that can express non-regular properties for which known extensions of MSO with equality of path length are undecidable. We show that our variant of CTL is decidable and that the model-checking problem is in Delta_3^P = P^{NP^NP}, and is DP-hard. We analogously consider quantifier exchange in extensions of CTL, and we present operators defined using basic operators of CTL* that express the occurrence of infinitely many synchronization points. We show that the model-checking problem remains in Delta_3^P. The distinguishing power of CTL and of our new logic coincide if the Next operator is allowed in the logics, thus the classical bisimulation quotient can be used for state-space reduction before model checking.
AU - Chatterjee, Krishnendu
AU - Doyen, Laurent
ID - 1070
TI - Computation tree logic for synchronization properties
VL - 55
ER -
TY - CONF
AB - We consider data-structures for answering reachability and distance queries on constant-treewidth graphs with n nodes, on the standard RAM computational model with wordsize W=Theta(log n). Our first contribution is a data-structure that after O(n) preprocessing time, allows (1) pair reachability queries in O(1) time; and (2) single-source reachability queries in O(n/log n) time. This is (asymptotically) optimal and is faster than DFS/BFS when answering more than a constant number of single-source queries. The data-structure uses at all times O(n) space. Our second contribution is a space-time tradeoff data-structure for distance queries. For any epsilon in [1/2,1], we provide a data-structure with polynomial preprocessing time that allows pair queries in O(n^{1-\epsilon} alpha(n)) time, where alpha is the inverse of the Ackermann function, and at all times uses O(n^epsilon) space. The input graph G is not considered in the space complexity.
AU - Chatterjee, Krishnendu
AU - Ibsen-Jensen, Rasmus
AU - Pavlogiannis, Andreas
ID - 1071
TI - Optimal reachability and a space time tradeoff for distance queries in constant treewidth graphs
VL - 57
ER -
TY - JOUR
AB - The asymmetric localization of proteins in the plasma membrane domains of eukaryotic cells is a fundamental manifestation of cell polarity that is central to multicellular organization and developmental patterning. In plants, the mechanisms underlying the polar localization of cargo proteins are still largely unknown and appear to be fundamentally distinct from those operating in mammals. Here, we present a systematic, quantitative comparative analysis of the polar delivery and subcellular localization of proteins that characterize distinct polar plasma membrane domains in plant cells. The combination of microscopic analyses and computational modeling revealed a mechanistic framework common to diverse polar cargos and underlying the establishment and maintenance of apical, basal, and lateral polar domains in plant cells. This mechanism depends on the polar secretion, constitutive endocytic recycling, and restricted lateral diffusion of cargos within the plasma membrane. Moreover, our observations suggest that polar cargo distribution involves the individual protein potential to form clusters within the plasma membrane and interact with the extracellular matrix. Our observations provide insights into the shared cellular mechanisms of polar cargo delivery and polarity maintenance in plant cells.
AU - Łangowski, Łukasz
AU - Wabnik, Krzysztof T
AU - Li, Hongjiang
AU - Vanneste, Steffen
AU - Naramoto, Satoshi
AU - Tanaka, Hirokazu
AU - Friml, Jirí
ID - 1081
JF - Cell Discovery
TI - Cellular mechanisms for cargo delivery and polarity maintenance at different polar domains in plant cells
VL - 2
ER -
TY - CONF
AB - The main goal of the SCP-ECG standard is to address ECG data and related metadata structuring, semantics and syntax, with the objective of facilitating interoperability and thus supporting and promoting the exchange of the relevant information for unary and serial ECG diagnosis. Starting with version V3.0, the standard now also provides support for the storage of continuous, long-term ECG recordings and affords a repository for selected ECG sequences and the related metadata to accommodate stress tests, drug trials and protocol-based ECG recordings. The global and per-lead measurements sections have been extended and three new sections have been introduced for storing beat-by-beat and/or spike-by-spike measurements
and annotations. The used terminology and the provided measurements and annotations have been harmonized with the ISO/IEEE 11073-10102 Annotated ECG standard. Emphasis has also been put on harmonizing the Universal Statement Codes with the CDISC and the categorized AHA statement codes and similarly the drug and implanted devices codes with the ATC and NASPE/BPEG codes.
AU - Rubel, Paul
AU - Pani, Danilo
AU - Schlögl, Alois
AU - Fayn, Jocelyne
AU - Badilini, Fabio
AU - Macfarlane, Peter
AU - Varri, Alpo
ID - 10810
SN - 2325-887X
T2 - 2016 Computing in Cardiology Conference
TI - SCP-ECG V3.0: An enhanced standard communication protocol for computer-assisted electrocardiography
VL - 43
ER -
TY - CONF
AB - In many applications, it is desirable to extract only the relevant aspects of data. A principled way to do this is the information bottleneck (IB) method, where one seeks a code that maximises information about a relevance variable, Y, while constraining the information encoded about the original data, X. Unfortunately however, the IB method is computationally demanding when data are high-dimensional and/or non-gaussian. Here we propose an approximate variational scheme for maximising a lower bound on the IB objective, analogous to variational EM. Using this method, we derive an IB algorithm to recover features that are both relevant and sparse. Finally, we demonstrate how kernelised versions of the algorithm can be used to address a broad range of problems with non-linear relation between X and Y.
AU - Chalk, Matthew J
AU - Marre, Olivier
AU - Tkacik, Gasper
ID - 1082
TI - Relevant sparse codes with variational information bottleneck
VL - 29
ER -
TY - JOUR
AB - Cholecystokinin-expressing interneurons (CCK-INs) mediate behavior state-dependent inhibition in cortical circuits and themselves receive strong GABAergic input. However, it remains unclear to what extent GABABreceptors (GABABRs) contribute to their inhibitory control. Using immunoelectron microscopy, we found that CCK-INs in the rat hippocampus possessed high levels of dendritic GABABRs and KCTD12 auxiliary proteins, whereas postsynaptic effector Kir3 channels were present at lower levels. Consistently, whole-cell recordings revealed slow GABABR-mediated inhibitory postsynaptic currents (IPSCs) in most CCK-INs. In spite of the higher surface density of GABABRs in CCK-INs than in CA1 principal cells, the amplitudes of IPSCs were comparable, suggesting that the expression of Kir3 channels is the limiting factor for the GABABR currents in these INs. Morphological analysis showed that CCK-INs were diverse, comprising perisomatic-targeting basket cells (BCs), as well as dendrite-targeting (DT) interneurons, including a previously undescribed DT type. GABABR-mediated IPSCs in CCK-INs were large in BCs, but small in DT subtypes. In response to prolonged activation, GABABR-mediated currents displayed strong desensitization, which was absent in KCTD12-deficient mice. This study highlights that GABABRs differentially control CCK-IN subtypes, and the kinetics and desensitization of GABABR-mediated currents are modulated by KCTD12 proteins.
AU - Booker, Sam
AU - Althof, Daniel
AU - Gross, Anna
AU - Loreth, Desiree
AU - Müller, Johanna
AU - Unger, Andreas
AU - Fakler, Bernd
AU - Varro, Andrea
AU - Watanabe, Masahiko
AU - Gassmann, Martin
AU - Bettler, Bernhard
AU - Shigemoto, Ryuichi
AU - Vida, Imre
AU - Kulik, Ákos
ID - 1083
IS - 3
JF - Cerebral Cortex
TI - KCTD12 auxiliary proteins modulate kinetics of GABAB receptor-mediated inhibition in Cholecystokinin-containing interneurons
VL - 27
ER -
TY - CONF
AB - While weighted automata provide a natural framework to express quantitative properties, many basic properties like average response time cannot be expressed with weighted automata. Nested weighted automata extend weighted automata and consist of a master automaton and a set of slave automata that are invoked by the master automaton. Nested weighted automata are strictly more expressive than weighted automata (e.g., average response time can be expressed with nested weighted automata), but the basic decision questions have higher complexity (e.g., for deterministic automata, the emptiness question for nested weighted automata is PSPACE-hard, whereas the corresponding complexity for weighted automata is PTIME). We consider a natural subclass of nested weighted automata where at any point at most a bounded number k of slave automata can be active. We focus on automata whose master value function is the limit average. We show that these nested weighted automata with bounded width are strictly more expressive than weighted automata (e.g., average response time with no overlapping requests can be expressed with bound k=1, but not with non-nested weighted automata). We show that the complexity of the basic decision problems (i.e., emptiness and universality) for the subclass with k constant matches the complexity for weighted automata. Moreover, when k is part of the input given in unary we establish PSPACE-completeness.
AU - Chatterjee, Krishnendu
AU - Henzinger, Thomas A
AU - Otop, Jan
ID - 1090
TI - Nested weighted limit-average automata of bounded width
VL - 58
ER -
TY - CONF
AB - We introduce a general class of distances (metrics) between Markov chains, which are based on linear behaviour. This class encompasses distances given topologically (such as the total variation distance or trace distance) as well as by temporal logics or automata. We investigate which of the distances can be approximated by observing the systems, i.e. by black-box testing or simulation, and we provide both negative and positive results.
AU - Daca, Przemyslaw
AU - Henzinger, Thomas A
AU - Kretinsky, Jan
AU - Petrov, Tatjana
ID - 1093
TI - Linear distances between Markov chains
VL - 59
ER -
TY - CHAP
AB - Immunogold labeling of freeze-fracture replicas has recently been used for high-resolution visualization of protein localization in electron microscopy. This method has higher labeling efficiency than conventional immunogold methods for membrane molecules allowing precise quantitative measurements. However, one of the limitations of freeze-fracture replica immunolabeling is difficulty in keeping structural orientation and identifying labeled profiles in complex tissues like brain. The difficulty is partly due to fragmentation of freeze-fracture replica preparations during labeling procedures and limited morphological clues on the replica surface. To overcome these issues, we introduce here a grid-glued replica method combined with SEM observation. This method allows histological staining before dissolving the tissue and easy handling of replicas during immunogold labeling, and keeps the whole replica surface intact without fragmentation. The procedure described here is also useful for matched double-replica analysis allowing further identification of labeled profiles in corresponding P-face and E-face.
AU - Harada, Harumi
AU - Shigemoto, Ryuichi
ID - 1094
T2 - High-Resolution Imaging of Cellular Proteins
TI - Immunogold protein localization on grid-glued freeze-fracture replicas
VL - 1474
ER -
TY - CONF
AB - The semantics of concurrent data structures is usually given by a sequential specification and a consistency condition. Linearizability is the most popular consistency condition due to its simplicity and general applicability. Nevertheless, for applications that do not require all guarantees offered by linearizability, recent research has focused on improving performance and scalability of concurrent data structures by relaxing their semantics. In this paper, we present local linearizability, a relaxed consistency condition that is applicable to container-type concurrent data structures like pools, queues, and stacks. While linearizability requires that the effect of each operation is observed by all threads at the same time, local linearizability only requires that for each thread T, the effects of its local insertion operations and the effects of those removal operations that remove values inserted by T are observed by all threads at the same time. We investigate theoretical and practical properties of local linearizability and its relationship to many existing consistency conditions. We present a generic implementation method for locally linearizable data structures that uses existing linearizable data structures as building blocks. Our implementations show performance and scalability improvements over the original building blocks and outperform the fastest existing container-type implementations.
AU - Haas, Andreas
AU - Henzinger, Thomas A
AU - Holzer, Andreas
AU - Kirsch, Christoph
AU - Lippautz, Michael
AU - Payer, Hannes
AU - Sezgin, Ali
AU - Sokolova, Ana
AU - Veith, Helmut
ID - 1095
T2 - Leibniz International Proceedings in Informatics
TI - Local linearizability for concurrent container-type data structures
VL - 59
ER -
TY - JOUR
AU - Schwayer, Cornelia
AU - Sikora, Mateusz K
AU - Slovakova, Jana
AU - Kardos, Roland
AU - Heisenberg, Carl-Philipp J
ID - 1096
IS - 6
JF - Developmental Cell
TI - Actin rings of power
VL - 37
ER -
TY - CONF
AB - We present an interactive system for computational design, optimization, and fabrication of multicopters. Our computational approach allows non-experts to design, explore, and evaluate a wide range of different multicopters. We provide users with an intuitive interface for assembling a multicopter from a collection of components (e.g., propellers, motors, and carbon fiber rods). Our algorithm interactively optimizes shape and controller parameters of the current design to ensure its proper operation. In addition, we allow incorporating a variety of other metrics (such as payload, battery usage, size, and cost) into the design process and exploring tradeoffs between them. We show the efficacy of our method and system by designing, optimizing, fabricating, and operating multicopters with complex geometries and propeller configurations. We also demonstrate the ability of our optimization algorithm to improve the multicopter performance under different metrics.
AU - Du, Tao
AU - Schulz, Adriana
AU - Zhu, Bo
AU - Bickel, Bernd
AU - Matusik, Wojciech
ID - 1097
IS - 6
TI - Computational multicopter design
VL - 35
ER -
TY - CONF
AB - Better understanding of the potential benefits of information transfer and representation learning is an important step towards the goal of building intelligent systems that are able to persist in the world and learn over time. In this work, we consider a setting where the learner encounters a stream of tasks but is able to retain only limited information from each encountered task, such as a learned predictor. In contrast to most previous works analyzing this scenario, we do not make any distributional assumptions on the task generating process. Instead, we formulate a complexity measure that captures the diversity of the observed tasks. We provide a lifelong learning algorithm with error guarantees for every observed task (rather than on average). We show sample complexity reductions in comparison to solving every task in isolation in terms of our task complexity measure. Further, our algorithmic framework can naturally be viewed as learning a representation from encountered tasks with a neural network.
AU - Pentina, Anastasia
AU - Urner, Ruth
ID - 1098
TI - Lifelong learning with weighted majority votes
VL - 29
ER -
TY - CONF
AB - We present FlexMolds, a novel computational approach to automatically design flexible, reusable molds that, once 3D printed, allow us to physically fabricate, by means of liquid casting, multiple copies of complex shapes with rich surface details and complex topology. The approach to design such flexible molds is based on a greedy bottom-up search of possible cuts over an object, evaluating for each possible cut the feasibility of the resulting mold. We use a dynamic simulation approach to evaluate candidate molds, providing a heuristic to generate forces that are able to open, detach, and remove a complex mold from the object it surrounds. We have tested the approach with a number of objects with nontrivial shapes and topologies.
AU - Malomo, Luigi
AU - Pietroni, Nico
AU - Bickel, Bernd
AU - Cignoni, Paolo
ID - 1099
IS - 6
TI - FlexMolds: Automatic design of flexible shells for molding
VL - 35
ER -
TY - JOUR
AB - Optical sensors based on the phenomenon of Förster resonance energy transfer (FRET) are powerful tools that have advanced the study of small molecules in biological systems. However, sensor construction is not trivial and often requires multiple rounds of engineering or an ability to screen large numbers of variants. A method that would allow the accurate rational design of FRET sensors would expedite the production of biologically useful sensors. Here, we present Rangefinder, a computational algorithm that allows rapid in silico screening of dye attachment sites in a ligand-binding protein for the conjugation of a dye molecule to act as a Förster acceptor for a fused fluorescent protein. We present three ratiometric fluorescent sensors designed with Rangefinder, including a maltose sensor with a dynamic range of >300% and the first sensors for the most abundant sialic acid in human cells, N-acetylneuraminic acid. Provided a ligand-binding protein exists, it is our expectation that this model will facilitate the design of an optical sensor for any small molecule of interest.
AU - Mitchell, Joshua
AU - Whitfield, Jason
AU - Zhang, William
AU - Henneberger, Christian
AU - Janovjak, Harald L
AU - O'Mara, Megan
AU - Jackson, Colin
ID - 1101
IS - 11
JF - ACS SENSORS
TI - Rangefinder: A semisynthetic FRET sensor design algorithm
VL - 1
ER -
TY - CONF
AB - Weakly-supervised object localization methods tend to fail for object classes that consistently co-occur with the same background elements, e.g. trains on tracks. We propose a method to overcome these failures by adding a very small amount of model-specific additional annotation. The main idea is to cluster a deep network\'s mid-level representations and assign object or distractor labels to each cluster. Experiments show substantially improved localization results on the challenging ILSVC2014 dataset for bounding box detection and the PASCAL VOC2012 dataset for semantic segmentation.
AU - Kolesnikov, Alexander
AU - Lampert, Christoph
ID - 1102
T2 - Proceedings of the British Machine Vision Conference 2016
TI - Improving weakly-supervised object localization by micro-annotation
VL - 2016-September
ER -
TY - CONF
AB - We propose two parallel state-space-exploration algorithms for hybrid automaton (HA), with the goal of enhancing performance on multi-core shared-memory systems. The first uses the parallel, breadth-first-search algorithm (PBFS) of the SPIN model checker, when traversing the discrete modes of the HA, and enhances it with a parallel exploration of the continuous states within each mode. We show that this simple-minded extension of PBFS does not provide the desired load balancing in many HA benchmarks. The second algorithm is a task-parallel BFS algorithm (TP-BFS), which uses a cheap precomputation of the cost associated with the post operations (both continuous and discrete) in order to improve load balancing. We illustrate the TP-BFS and the cost precomputation of the post operators on a support-function-based algorithm for state-space exploration. The performance comparison of the two algorithms shows that, in general, TP-BFS provides a better utilization/load-balancing of the CPU. Both algorithms are implemented in the model checker XSpeed. Our experiments show a maximum speed-up of more than 2000 χ on a navigation benchmark, with respect to SpaceEx LGG scenario. In order to make the comparison fair, we employed an equal number of post operations in both tools. To the best of our knowledge, this paper represents the first attempt to provide parallel, reachability-analysis algorithms for HA.
AU - Gurung, Amit
AU - Deka, Arup
AU - Bartocci, Ezio
AU - Bogomolov, Sergiy
AU - Grosu, Radu
AU - Ray, Rajarshi
ID - 1103
TI - Parallel reachability analysis for hybrid systems
ER -
TY - CONF
AB - Jointly characterizing neural responses in terms of several external variables promises novel insights into circuit function, but remains computationally prohibitive in practice. Here we use gaussian process (GP) priors and exploit recent advances in fast GP inference and learning based on Kronecker methods, to efficiently estimate multidimensional nonlinear tuning functions. Our estimator require considerably less data than traditional methods and further provides principled uncertainty estimates. We apply these tools to hippocampal recordings during open field exploration and use them to characterize the joint dependence of CA1 responses on the position of the animal and several other variables, including the animal\'s speed, direction of motion, and network oscillations.Our results provide an unprecedentedly detailed quantification of the tuning of hippocampal neurons. The model\'s generality suggests that our approach can be used to estimate neural response properties in other brain regions.
AU - Savin, Cristina
AU - Tkacik, Gasper
ID - 1105
TI - Estimating nonlinear neural response functions using GP priors and Kronecker methods
VL - 29
ER -
TY - CONF
AB - We present a coherent microwave to telecom signal converter based on the electro-optical effect using a crystalline WGM-resonator coupled to a 3D microwave cavity, achieving high photon conversion efficiency of 0.1% with MHz bandwidth.
AU - Rueda, Alfredo
AU - Sedlmeir, Florian
AU - Collodo, Michele
AU - Vogl, Ulrich
AU - Stiller, Birgit
AU - Schunk, Georg
AU - Strekalov, Dimitry
AU - Marquardt, Christoph
AU - Fink, Johannes M
AU - Painter, Oskar
AU - Leuchs, Gerd
AU - Schwefel, Harald
ID - 1115
TI - Efficient single sideband microwave to optical conversion using a LiNbO inf 3 inf WGM-resonator
ER -
TY - THES
AB - Horizontal gene transfer (HGT), the lateral acquisition of genes across existing species
boundaries, is a major evolutionary force shaping microbial genomes that facilitates
adaptation to new environments as well as resistance to antimicrobial drugs. As such,
understanding the mechanisms and constraints that determine the outcomes of HGT
events is crucial to understand the dynamics of HGT and to design better strategies to
overcome the challenges that originate from it.
Following the insertion and expression of a newly transferred gene, the success of an
HGT event will depend on the fitness effect it has on the recipient (host) cell. Therefore,
predicting the impact of HGT on the genetic composition of a population critically
depends on the distribution of fitness effects (DFE) of horizontally transferred genes.
However, to date, we have little knowledge of the DFE of newly transferred genes, and
hence little is known about the shape and scale of this distribution.
It is particularly important to better understand the selective barriers that determine
the fitness effects of newly transferred genes. In spite of substantial bioinformatics
efforts to identify horizontally transferred genes and selective barriers, a systematic
experimental approach to elucidate the roles of different selective barriers in defining
the fate of a transfer event has largely been absent. Similarly, although the fact that
environment might alter the fitness effect of a horizontally transferred gene may seem
obvious, little attention has been given to it in a systematic experimental manner.
In this study, we developed a systematic experimental approach that consists of
transferring 44 arbitrarily selected Salmonella typhimurium orthologous genes into an
Escherichia coli host, and estimating the fitness effects of these transferred genes at a
constant expression level by performing competition assays against the wild type.
In chapter 2, we performed one-to-one competition assays between a mutant strain
carrying a transferred gene and the wild type strain. By using flow cytometry we
estimated selection coefficients for the transferred genes with a precision level of 10-3,and obtained the DFE of horizontally transferred genes. We then investigated if these
fitness effects could be predicted by any of the intrinsic properties of the genes, namely,
functional category, degree of complexity (protein-protein interactions), GC content,
codon usage and length. Our analyses revealed that the functional category and length
of the genes act as potential selective barriers. Finally, using the same procedure with
the endogenous E. coli orthologs of these 44 genes, we demonstrated that gene dosage is
the most prominent selective barrier to HGT.
In chapter 3, using the same set of genes we investigated the role of environment on the
success of HGT events. Under six different environments with different levels of stress
we performed more complex competition assays, where we mixed all 44 mutant strains
carrying transferred genes with the wild type strain. To estimate the fitness effects of
genes relative to wild type we used next generation sequencing. We found that the DFEs
of horizontally transferred genes are highly dependent on the environment, with
abundant gene–by-environment interactions. Furthermore, we demonstrated a
relationship between average fitness effect of a gene across all environments and its
environmental variance, and thus its predictability. Finally, in spite of the fitness effects
of genes being highly environment-dependent, we still observed a common shape of
DFEs across all tested environments.
AU - Acar, Hande
ID - 1121
TI - Selective barriers to horizontal gene transfer
ER -
TY - THES
AB - Computer graphics is an extremely exciting field for two reasons. On the one hand,
there is a healthy injection of pragmatism coming from the visual effects industry
that want robust algorithms that work so they can produce results at an increasingly
frantic pace. On the other hand, they must always try to push the envelope and
achieve the impossible to wow their audiences in the next blockbuster, which means
that the industry has not succumb to conservatism, and there is plenty of room to
try out new and crazy ideas if there is a chance that it will pan into something
useful.
Water simulation has been in visual effects for decades, however it still remains
extremely challenging because of its high computational cost and difficult artdirectability.
The work in this thesis tries to address some of these difficulties.
Specifically, we make the following three novel contributions to the state-of-the-art
in water simulation for visual effects.
First, we develop the first algorithm that can convert any sequence of closed
surfaces in time into a moving triangle mesh. State-of-the-art methods at the time
could only handle surfaces with fixed connectivity, but we are the first to be able to
handle surfaces that merge and split apart. This is important for water simulation
practitioners, because it allows them to convert splashy water surfaces extracted
from particles or simulated using grid-based level sets into triangle meshes that can
be either textured and enhanced with extra surface dynamics as a post-process.
We also apply our algorithm to other phenomena that merge and split apart, such
as morphs and noisy reconstructions of human performances.
Second, we formulate a surface-based energy that measures the deviation of a
water surface froma physically valid state. Such discrepancies arise when there is a
mismatch in the degrees of freedom between the water surface and the underlying
physics solver. This commonly happens when practitioners use a moving triangle
mesh with a grid-based physics solver, or when high-resolution grid-based surfaces
are combined with low-resolution physics. Following the direction of steepest
descent on our surface-based energy, we can either smooth these artifacts or turn
them into high-resolution waves by interpreting the energy as a physical potential.
Third, we extend state-of-the-art techniques in non-reflecting boundaries to handle spatially and time-varying background flows. This allows a novel new
workflow where practitioners can re-simulate part of an existing simulation, such
as removing a solid obstacle, adding a new splash or locally changing the resolution.
Such changes can easily lead to new waves in the re-simulated region that would
reflect off of the new simulation boundary, effectively ruining the illusion of a
seamless simulation boundary between the existing and new simulations. Our
non-reflecting boundaries makes sure that such waves are absorbed.
AU - Bojsen-Hansen, Morten
ID - 1122
TI - Tracking, correcting and absorbing water surface waves
ER -
TY - THES
AB - Motivated by topological Tverberg-type problems in topological combinatorics and by classical
results about embeddings (maps without double points), we study the question whether a finite
simplicial complex K can be mapped into Rd without triple, quadruple, or, more generally, r-fold points (image points with at least r distinct preimages), for a given multiplicity r ≤ 2. In particular, we are interested in maps f : K → Rd that have no global r -fold intersection points, i.e., no r -fold points with preimages in r pairwise disjoint simplices of K , and we seek necessary and sufficient conditions for the existence of such maps.
We present higher-multiplicity analogues of several classical results for embeddings, in particular of the completeness of the Van Kampen obstruction for embeddability of k -dimensional
complexes into R2k , k ≥ 3. Speciffically, we show that under suitable restrictions on the dimensions(viz., if dimK = (r ≥ 1)k and d = rk \ for some k ≥ 3), a well-known deleted product criterion (DPC ) is not only necessary but also sufficient for the existence of maps without global r -fold points. Our main technical tool is a higher-multiplicity version of the classical Whitney trick , by which pairs of isolated r -fold points of opposite sign can be eliminated by local modiffications of the map, assuming codimension d – dimK ≥ 3.
An important guiding idea for our work was that suffciency of the DPC, together with an old
result of Özaydin's on the existence of equivariant maps, might yield an approach to disproving the remaining open cases of the the long-standing topological Tverberg conjecture , i.e., to construct maps from the N -simplex σN to Rd without r-Tverberg points when r not a prime power and
N = (d + 1)(r – 1). Unfortunately, our proof of the sufficiency of the DPC requires codimension d – dimK ≥ 3, which is not satisfied for K = σN .
In 2015, Frick [16] found a very elegant way to overcome this \codimension 3 obstacle" and
to construct the first counterexamples to the topological Tverberg conjecture for all parameters(d; r ) with d ≥ 3r + 1 and r not a prime power, by a reduction1 to a suitable lower-dimensional skeleton, for which the codimension 3 restriction is satisfied and maps without r -Tverberg points exist by Özaydin's result and sufficiency of the DPC.
In this thesis, we present a different construction (which does not use the constraint method) that yields counterexamples for d ≥ 3r , r not a prime power.
AU - Mabillard, Isaac
ID - 1123
TI - Eliminating higher-multiplicity intersections: an r-fold Whitney trick for the topological Tverberg conjecture
ER -
TY - THES
AU - Morri, Maurizio
ID - 1124
TI - Optical functionalization of human class A orphan G-protein coupled receptors
ER -
TY - THES
AB - Natural environments are never constant but subject to spatial and temporal change on
all scales, increasingly so due to human activity. Hence, it is crucial to understand the
impact of environmental variation on evolutionary processes. In this thesis, I present
three topics that share the common theme of environmental variation, yet illustrate its
effect from different perspectives.
First, I show how a temporally fluctuating environment gives rise to second-order
selection on a modifier for stress-induced mutagenesis. Without fluctuations, when
populations are adapted to their environment, mutation rates are minimized. I argue
that a stress-induced mutator mechanism may only be maintained if the population is
repeatedly subjected to diverse environmental challenges, and I outline implications of
the presented results to antibiotic treatment strategies.
Second, I discuss my work on the evolution of dispersal. Besides reproducing
known results about the effect of heterogeneous habitats on dispersal, it identifies
spatial changes in dispersal type frequencies as a source for selection for increased
propensities to disperse. This concept contains effects of relatedness that are known
to promote dispersal, and I explain how it identifies other forces selecting for dispersal
and puts them on a common scale.
Third, I analyse genetic variances of phenotypic traits under multivariate stabilizing
selection. For the case of constant environments, I generalize known formulae of
equilibrium variances to multiple traits and discuss how the genetic variance of a focal
trait is influenced by selection on background traits. I conclude by presenting ideas and
preliminary work aiming at including environmental fluctuations in the form of moving
trait optima into the model.
AU - Novak, Sebastian
ID - 1125
TI - Evolutionary proccesses in variable emvironments
ER -
TY - THES
AB - Traditionally machine learning has been focusing on the problem of solving a single
task in isolation. While being quite well understood, this approach disregards an
important aspect of human learning: when facing a new problem, humans are able to
exploit knowledge acquired from previously learned tasks. Intuitively, access to several
problems simultaneously or sequentially could also be advantageous for a machine
learning system, especially if these tasks are closely related. Indeed, results of many
empirical studies have provided justification for this intuition. However, theoretical
justifications of this idea are rather limited.
The focus of this thesis is to expand the understanding of potential benefits of information
transfer between several related learning problems. We provide theoretical
analysis for three scenarios of multi-task learning - multiple kernel learning, sequential
learning and active task selection. We also provide a PAC-Bayesian perspective on
lifelong learning and investigate how the task generation process influences the generalization
guarantees in this scenario. In addition, we show how some of the obtained
theoretical results can be used to derive principled multi-task and lifelong learning
algorithms and illustrate their performance on various synthetic and real-world datasets.
AU - Pentina, Anastasia
ID - 1126
TI - Theoretical foundations of multi-task lifelong learning
ER -