TY - CONF
AB - The synthesis problem asks for the automatic construction of a system from its specification. In the traditional setting, the system is “constructed from scratch” rather than composed from reusable components. However, this is rare in practice, and almost every non-trivial software system relies heavily on the use of libraries of reusable components. Recently, Lustig and Vardi introduced dataflow and controlflow synthesis from libraries of reusable components. They proved that dataflow synthesis is undecidable, while controlflow synthesis is decidable. The problem of controlflow synthesis from libraries of probabilistic components was considered by Nain, Lustig and Vardi, and was shown to be decidable for qualitative analysis (that asks that the specification be satisfied with probability 1). Our main contribution for controlflow synthesis from probabilistic components is to establish better complexity bounds for the qualitative analysis problem, and to show that the more general quantitative problem is undecidable. For the qualitative analysis, we show that the problem (i) is EXPTIME-complete when the specification is given as a deterministic parity word automaton, improving the previously known 2EXPTIME upper bound; and (ii) belongs to UP ∩ coUP and is parity-games hard, when the specification is given directly as a parity condition on the components, improving the previously known EXPTIME upper bound.
AU - Chatterjee, Krishnendu
AU - Doyen, Laurent
AU - Vardi, Moshe
ID - 1609
TI - The complexity of synthesis from probabilistic components
VL - 9135
ER -
TY - CONF
AB - The edit distance between two words w1, w2 is the minimal number of word operations (letter insertions, deletions, and substitutions) necessary to transform w1 to w2. The edit distance generalizes to languages L1,L2, where the edit distance is the minimal number k such that for every word from L1 there exists a word in L2 with edit distance at most k. We study the edit distance computation problem between pushdown automata and their subclasses. The problem of computing edit distance to pushdown automata is undecidable, and in practice, the interesting question is to compute the edit distance from a pushdown automaton (the implementation, a standard model for programs with recursion) to a regular language (the specification). In this work, we present a complete picture of decidability and complexity for deciding whether, for a given threshold k, the edit distance from a pushdown automaton to a finite automaton is at most k.
AU - Chatterjee, Krishnendu
AU - Henzinger, Thomas A
AU - Ibsen-Jensen, Rasmus
AU - Otop, Jan
ID - 1610
IS - Part II
TI - Edit distance for pushdown automata
VL - 9135
ER -
TY - JOUR
AB - Biosensors for signaling molecules allow the study of physiological processes by bringing together the fields of protein engineering, fluorescence imaging, and cell biology. Construction of genetically encoded biosensors generally relies on the availability of a binding "core" that is both specific and stable, which can then be combined with fluorescent molecules to create a sensor. However, binding proteins with the desired properties are often not available in nature and substantial improvement to sensors can be required, particularly with regard to their durability. Ancestral protein reconstruction is a powerful protein-engineering tool able to generate highly stable and functional proteins. In this work, we sought to establish the utility of ancestral protein reconstruction to biosensor development, beginning with the construction of an l-arginine biosensor. l-arginine, as the immediate precursor to nitric oxide, is an important molecule in many physiological contexts including brain function. Using a combination of ancestral reconstruction and circular permutation, we constructed a Förster resonance energy transfer (FRET) biosensor for l-arginine (cpFLIPR). cpFLIPR displays high sensitivity and specificity, with a Kd of ∼14 μM and a maximal dynamic range of 35%. Importantly, cpFLIPR was highly robust, enabling accurate l-arginine measurement at physiological temperatures. We established that cpFLIPR is compatible with two-photon excitation fluorescence microscopy and report l-arginine concentrations in brain tissue.
AU - Whitfield, Jason
AU - Zhang, William
AU - Herde, Michel
AU - Clifton, Ben
AU - Radziejewski, Johanna
AU - Janovjak, Harald L
AU - Henneberger, Christian
AU - Jackson, Colin
ID - 1611
IS - 9
JF - Protein Science
TI - Construction of a robust and sensitive arginine biosensor through ancestral protein reconstruction
VL - 24
ER -
TY - JOUR
AB - GABAergic perisoma-inhibiting fast-spiking interneurons (PIIs) effectively control the activity of large neuron populations by their wide axonal arborizations. It is generally assumed that the output of one PII to its target cells is strong and rapid. Here, we show that, unexpectedly, both strength and time course of PII-mediated perisomatic inhibition change with distance between synaptically connected partners in the rodent hippocampus. Synaptic signals become weaker due to lower contact numbers and decay more slowly with distance, very likely resulting from changes in GABAA receptor subunit composition. When distance-dependent synaptic inhibition is introduced to a rhythmically active neuronal network model, randomly driven principal cell assemblies are strongly synchronized by the PIIs, leading to higher precision in principal cell spike times than in a network with uniform synaptic inhibition.
AU - Strüber, Michael
AU - Jonas, Peter M
AU - Bartos, Marlene
ID - 1614
IS - 4
JF - PNAS
TI - Strength and duration of perisomatic GABAergic inhibition depend on distance between synaptically connected cells
VL - 112
ER -
TY - JOUR
AB - Loss-of-function mutations in the synaptic adhesion protein Neuroligin-4 are among the most common genetic abnormalities associated with autism spectrum disorders, but little is known about the function of Neuroligin-4 and the consequences of its loss. We assessed synaptic and network characteristics in Neuroligin-4 knockout mice, focusing on the hippocampus as a model brain region with a critical role in cognition and memory, and found that Neuroligin-4 deletion causes subtle defects of the protein composition and function of GABAergic synapses in the hippocampal CA3 region. Interestingly, these subtle synaptic changes are accompanied by pronounced perturbations of γ-oscillatory network activity, which has been implicated in cognitive function and is altered in multiple psychiatric and neurodevelopmental disorders. Our data provide important insights into the mechanisms by which Neuroligin-4-dependent GABAergic synapses may contribute to autism phenotypes and indicate new strategies for therapeutic approaches.
AU - Hammer, Matthieu
AU - Krueger Burg, Dilja
AU - Tuffy, Liam
AU - Cooper, Benjamin
AU - Taschenberger, Holger
AU - Goswami, Sarit
AU - Ehrenreich, Hannelore
AU - Jonas, Peter M
AU - Varoqueaux, Frederique
AU - Rhee, Jeong
AU - Brose, Nils
ID - 1615
IS - 3
JF - Cell Reports
TI - Perturbed hippocampal synaptic inhibition and γ-oscillations in a neuroligin-4 knockout mouse model of autism
VL - 13
ER -
TY - JOUR
AB - CCL19 and CCL21 are chemokines involved in the trafficking of immune cells, particularly within the lymphatic system, through activation of CCR7. Concurrent expression of PSGL-1 and CCR7 in naive T-cells enhances recruitment of these cells to secondary lymphoid organs by CCL19 and CCL21. Here the solution structure of CCL19 is reported. It contains a canonical chemokine domain. Chemical shift mapping shows the N-termini of PSGL-1 and CCR7 have overlapping binding sites for CCL19 and binding is competitive. Implications for the mechanism of PSGL-1's enhancement of resting T-cell recruitment are discussed.
AU - Veldkamp, Christopher
AU - Kiermaier, Eva
AU - Gabel Eissens, Skylar
AU - Gillitzer, Miranda
AU - Lippner, David
AU - Disilvio, Frank
AU - Mueller, Casey
AU - Wantuch, Paeton
AU - Chaffee, Gary
AU - Famiglietti, Michael
AU - Zgoba, Danielle
AU - Bailey, Asha
AU - Bah, Yaya
AU - Engebretson, Samantha
AU - Graupner, David
AU - Lackner, Emily
AU - Larosa, Vincent
AU - Medeiros, Tysha
AU - Olson, Michael
AU - Phillips, Andrew
AU - Pyles, Harley
AU - Richard, Amanda
AU - Schoeller, Scott
AU - Touzeau, Boris
AU - Williams, Larry
AU - Sixt, Michael K
AU - Peterson, Francis
ID - 1618
IS - 27
JF - Biochemistry
TI - Solution structure of CCL19 and identification of overlapping CCR7 and PSGL-1 binding sites
VL - 54
ER -
TY - JOUR
AB - Background
Photosynthetic cyanobacteria are attractive for a range of biotechnological applications including biofuel production. However, due to slow growth, screening of mutant libraries using microtiter plates is not feasible.
Results
We present a method for high-throughput, single-cell analysis and sorting of genetically engineered l-lactate-producing strains of Synechocystis sp. PCC6803. A microfluidic device is used to encapsulate single cells in picoliter droplets, assay the droplets for l-lactate production, and sort strains with high productivity. We demonstrate the separation of low- and high-producing reference strains, as well as enrichment of a more productive l-lactate-synthesizing population after UV-induced mutagenesis. The droplet platform also revealed population heterogeneity in photosynthetic growth and lactate production, as well as the presence of metabolically stalled cells.
Conclusions
The workflow will facilitate metabolic engineering and directed evolution studies and will be useful in studies of cyanobacteria biochemistry and physiology.
AU - Hammar, Petter
AU - Angermayr, Andreas
AU - Sjostrom, Staffan
AU - Van Der Meer, Josefin
AU - Hellingwerf, Klaas
AU - Hudson, Elton
AU - Joensson, Hakaan
ID - 1623
IS - 1
JF - Biotechnology for Biofuels
TI - Single-cell screening of photosynthetic growth and lactate production by cyanobacteria
VL - 8
ER -
TY - JOUR
AB - Population structure can facilitate evolution of cooperation. In a structured population, cooperators can form clusters which resist exploitation by defectors. Recently, it was observed that a shift update rule is an extremely strong amplifier of cooperation in a one dimensional spatial model. For the shift update rule, an individual is chosen for reproduction proportional to fecundity; the offspring is placed next to the parent; a random individual dies. Subsequently, the population is rearranged (shifted) until all individual cells are again evenly spaced out. For large population size and a one dimensional population structure, the shift update rule favors cooperation for any benefit-to-cost ratio greater than one. But every attempt to generalize shift updating to higher dimensions while maintaining its strong effect has failed. The reason is that in two dimensions the clusters are fragmented by the movements caused by rearranging the cells. Here we introduce the natural phenomenon of a repulsive force between cells of different types. After a birth and death event, the cells are being rearranged minimizing the overall energy expenditure. If the repulsive force is sufficiently high, shift becomes a strong promoter of cooperation in two dimensions.
AU - Pavlogiannis, Andreas
AU - Chatterjee, Krishnendu
AU - Adlam, Ben
AU - Nowak, Martin
ID - 1624
JF - Scientific Reports
TI - Cellular cooperation with shift updating and repulsion
VL - 5
ER -
TY - CONF
AB - In recent years we have seen numerous improvements on 3D scanning and tracking of human faces, greatly advancing the creation of digital doubles for film and video games. However, despite the high-resolution quality of the reconstruction approaches available, current methods are unable to capture one of the most important regions of the face - the eye region. In this work we present the first method for detailed spatio-temporal reconstruction of eyelids. Tracking and reconstructing eyelids is extremely challenging, as this region exhibits very complex and unique skin deformation where skin is folded under while opening the eye. Furthermore, eyelids are often only partially visible and obstructed due to selfocclusion and eyelashes. Our approach is to combine a geometric deformation model with image data, leveraging multi-view stereo, optical flow, contour tracking and wrinkle detection from local skin appearance. Our deformation model serves as a prior that enables reconstruction of eyelids even under strong self-occlusions caused by rolling and folding skin as the eye opens and closes. The output is a person-specific, time-varying eyelid reconstruction with anatomically plausible deformations. Our high-resolution detailed eyelids couple naturally with current facial performance capture approaches. As a result, our method can largely increase the fidelity of facial capture and the creation of digital doubles.
AU - Bermano, Amit
AU - Beeler, Thabo
AU - Kozlov, Yeara
AU - Bradley, Derek
AU - Bickel, Bernd
AU - Gross, Markus
ID - 1625
IS - 4
TI - Detailed spatio-temporal reconstruction of eyelids
VL - 34
ER -
TY - CONF
AB - This paper introduces "OmniAD," a novel data-driven pipeline to model and acquire the aerodynamics of three-dimensional rigid objects. Traditionally, aerodynamics are examined through elaborate wind tunnel experiments or expensive fluid dynamics computations, and are only measured for a small number of discrete wind directions. OmniAD allows the evaluation of aerodynamic forces, such as drag and lift, for any incoming wind direction using a novel representation based on spherical harmonics. Our datadriven technique acquires the aerodynamic properties of an object simply by capturing its falling motion using a single camera. Once model parameters are estimated, OmniAD enables realistic realtime simulation of rigid bodies, such as the tumbling and gliding of leaves, without simulating the surrounding air. In addition, we propose an intuitive user interface based on OmniAD to interactively design three-dimensional kites that actually fly. Various nontraditional kites were designed to demonstrate the physical validity of our model.
AU - Martin, Tobias
AU - Umetani, Nobuyuki
AU - Bickel, Bernd
ID - 1626
IS - 4
TI - OmniAD: Data-driven omni-directional aerodynamics
VL - 34
ER -
TY - CONF
AB - We present a computational tool for fabrication-oriented design of flexible rod meshes. Given a deformable surface and a set of deformed poses as input, our method automatically computes a printable rod mesh that, once manufactured, closely matches the input poses under the same boundary conditions. The core of our method is formed by an optimization scheme that adjusts the cross-sectional profiles of the rods and their rest centerline in order to best approximate the target deformations. This approach allows us to locally control the bending and stretching resistance of the surface with a single material, yielding high design flexibility and low fabrication cost.
AU - Pérez, Jesús
AU - Thomaszewski, Bernhard
AU - Coros, Stelian
AU - Bickel, Bernd
AU - Canabal, José
AU - Sumner, Robert
AU - Otaduy, Miguel
ID - 1627
IS - 4
TI - Design and fabrication of flexible rod meshes
VL - 34
ER -
TY - CONF
AB - We propose a method for fabricating deformable objects with spatially varying elasticity using 3D printing. Using a single, relatively stiff printer material, our method designs an assembly of smallscale microstructures that have the effect of a softer material at the object scale, with properties depending on the microstructure used in each part of the object. We build on work in the area of metamaterials, using numerical optimization to design tiled microstructures with desired properties, but with the key difference that our method designs families of related structures that can be interpolated to smoothly vary the material properties over a wide range. To create an object with spatially varying elastic properties, we tile the object's interior with microstructures drawn from these families, generating a different microstructure for each cell using an efficient algorithm to select compatible structures for neighboring cells. We show results computed for both 2D and 3D objects, validating several 2D and 3D printed structures using standard material tests as well as demonstrating various example applications.
AU - Schumacher, Christian
AU - Bickel, Bernd
AU - Rys, Jan
AU - Marschner, Steve
AU - Daraio, Chiara
AU - Gross, Markus
ID - 1628
IS - 4
TI - Microstructures to control elasticity in 3D printing
VL - 34
ER -
TY - CONF
AB - We present a method to learn and propagate shape placements in 2D polygonal scenes from a few examples provided by a user. The placement of a shape is modeled as an oriented bounding box. Simple geometric relationships between this bounding box and nearby scene polygons define a feature set for the placement. The feature sets of all example placements are then used to learn a probabilistic model over all possible placements and scenes. With this model, we can generate a new set of placements with similar geometric relationships in any given scene. We introduce extensions that enable propagation and generation of shapes in 3D scenes, as well as the application of a learned modeling session to large scenes without additional user interaction. These concepts allow us to generate complex scenes with thousands of objects with relatively little user interaction.
AU - Guerrero, Paul
AU - Jeschke, Stefan
AU - Wimmer, Michael
AU - Wonka, Peter
ID - 1630
IS - 4
TI - Learning shape placements by example
VL - 34
ER -
TY - CONF
AB - This paper presents a liquid simulation technique that enforces the incompressibility condition using a stream function solve instead of a pressure projection. Previous methods have used stream function techniques for the simulation of detailed single-phase flows, but a formulation for liquid simulation has proved elusive in part due to the free surface boundary conditions. In this paper, we introduce a stream function approach to liquid simulations with novel boundary conditions for free surfaces, solid obstacles, and solid-fluid coupling.
Although our approach increases the dimension of the linear system necessary to enforce incompressibility, it provides interesting and surprising benefits. First, the resulting flow is guaranteed to be divergence-free regardless of the accuracy of the solve. Second, our free-surface boundary conditions guarantee divergence-free motion even in the un-simulated air phase, which enables two-phase flow simulation by only computing a single phase. We implemented this method using a variant of FLIP simulation which only samples particles within a narrow band of the liquid surface, and we illustrate the effectiveness of our method for detailed two-phase flow simulations with complex boundaries, detailed bubble interactions, and two-way solid-fluid coupling.
AU - Ando, Ryoichi
AU - Thuerey, Nils
AU - Wojtan, Christopher J
ID - 1632
IS - 4
TI - A stream function solver for liquid simulations
VL - 34
ER -
TY - CONF
AB - We present a method for simulating brittle fracture under the assumptions of quasi-static linear elastic fracture mechanics (LEFM). Using the boundary element method (BEM) and Lagrangian crack-fronts, we produce highly detailed fracture surfaces. The computational cost of the BEM is alleviated by using a low-resolution mesh and interpolating the resulting stress intensity factors when propagating the high-resolution crack-front.
Our system produces physics-based fracture surfaces with high spatial and temporal resolution, taking spatial variation of material toughness and/or strength into account. It also allows for crack initiation to be handled separately from crack propagation, which is not only more reasonable from a physics perspective, but can also be used to control the simulation.
Separating the resolution of the crack-front from the resolution of the computational mesh increases the efficiency and therefore the amount of visual detail on the resulting fracture surfaces. The BEM also allows us to re-use previously computed blocks of the system matrix.
AU - Hahn, David
AU - Wojtan, Christopher J
ID - 1633
IS - 4
TI - High-resolution brittle fracture simulation with boundary elements
VL - 34
ER -
TY - CONF
AB - Simulating the delightful dynamics of soap films, bubbles, and foams has traditionally required the use of a fully three-dimensional many-phase Navier-Stokes solver, even though their visual appearance is completely dominated by the thin liquid surface. We depart from earlier work on soap bubbles and foams by noting that their dynamics are naturally described by a Lagrangian vortex sheet model in which circulation is the primary variable. This leads us to derive a novel circulation-preserving surface-only discretization of foam dynamics driven by surface tension on a non-manifold triangle mesh. We represent the surface using a mesh-based multimaterial surface tracker which supports complex bubble topology changes, and evolve the surface according to the ambient air flow induced by a scalar circulation field stored on the mesh. Surface tension forces give rise to a simple update rule for circulation, even at non-manifold Plateau borders, based on a discrete measure of signed scalar mean curvature. We further incorporate vertex constraints to enable the interaction of soap films with wires. The result is a method that is at once simple, robust, and efficient, yet able to capture an array of soap films behaviors including foam rearrangement, catenoid collapse, blowing bubbles, and double bubbles being pulled apart.
AU - Da, Fang
AU - Batty, Christopher
AU - Wojtan, Christopher J
AU - Grinspun, Eitan
ID - 1634
IS - 4
TI - Double bubbles sans toil and trouble: discrete circulation-preserving vortex sheets for soap films and foams
VL - 34
ER -
TY - JOUR
AB - We calculate a Ricci curvature lower bound for some classical examples of random walks, namely, a chain on a slice of the n-dimensional discrete cube (the so-called Bernoulli-Laplace model) and the random transposition shuffle of the symmetric group of permutations on n letters.
AU - Erbar, Matthias
AU - Maas, Jan
AU - Tetali, Prasad
ID - 1635
IS - 4
JF - Annales de la faculté des sciences de Toulouse
TI - Discrete Ricci curvature bounds for Bernoulli-Laplace and random transposition models
VL - 24
ER -
TY - CONF
AB - Constraint Satisfaction Problem (CSP) is a fundamental algorithmic problem that appears in many areas of Computer Science. It can be equivalently stated as computing a homomorphism R→ΓΓ between two relational structures, e.g. between two directed graphs. Analyzing its complexity has been a prominent research direction, especially for the fixed template CSPs where the right side ΓΓ is fixed and the left side R is unconstrained.
Far fewer results are known for the hybrid setting that restricts both sides simultaneously. It assumes that R belongs to a certain class of relational structures (called a structural restriction in this paper). We study which structural restrictions are effective, i.e. there exists a fixed template ΓΓ (from a certain class of languages) for which the problem is tractable when R is restricted, and NP-hard otherwise. We provide a characterization for structural restrictions that are closed under inverse homomorphisms. The criterion is based on the chromatic number of a relational structure defined in this paper; it generalizes the standard chromatic number of a graph.
As our main tool, we use the algebraic machinery developed for fixed template CSPs. To apply it to our case, we introduce a new construction called a “lifted language”. We also give a characterization for structural restrictions corresponding to minor-closed families of graphs, extend results to certain Valued CSPs (namely conservative valued languages), and state implications for (valued) CSPs with ordered variables and for the maximum weight independent set problem on some restricted families of graphs.
AU - Kolmogorov, Vladimir
AU - Rolinek, Michal
AU - Takhanov, Rustem
ID - 1636
TI - Effectiveness of structural restrictions for hybrid CSPs
VL - 9472
ER -
TY - CONF
AB - An instance of the Valued Constraint Satisfaction Problem (VCSP) is given by a finite set of variables, a finite domain of labels, and a sum of functions, each function depending on a subset of the variables. Each function can take finite values specifying costs of assignments of labels to its variables or the infinite value, which indicates an infeasible assignment. The goal is to find an assignment of labels to the variables that minimizes the sum. We study, assuming that P ≠ NP, how the complexity of this very general problem depends on the set of functions allowed in the instances, the so-called constraint language. The case when all allowed functions take values in {0, ∞} corresponds to ordinary CSPs, where one deals only with the feasibility issue and there is no optimization. This case is the subject of the Algebraic CSP Dichotomy Conjecture predicting for which constraint languages CSPs are tractable (i.e. solvable in polynomial time) and for which NP-hard. The case when all allowed functions take only finite values corresponds to finite-valued CSP, where the feasibility aspect is trivial and one deals only with the optimization issue. The complexity of finite-valued CSPs was fully classified by Thapper and Zivny. An algebraic necessary condition for tractability of a general-valued CSP with a fixed constraint language was recently given by Kozik and Ochremiak. As our main result, we prove that if a constraint language satisfies this algebraic necessary condition, and the feasibility CSP (i.e. the problem of deciding whether a given instance has a feasible solution) corresponding to the VCSP with this language is tractable, then the VCSP is tractable. The algorithm is a simple combination of the assumed algorithm for the feasibility CSP and the standard LP relaxation. As a corollary, we obtain that a dichotomy for ordinary CSPs would imply a dichotomy for general-valued CSPs.
AU - Kolmogorov, Vladimir
AU - Krokhin, Andrei
AU - Rolinek, Michal
ID - 1637
TI - The complexity of general-valued CSPs
ER -
TY - JOUR
AB - The mitochondrial respiratory chain, also known as the electron transport chain (ETC), is crucial to life, and energy production in the form of ATP is the main mitochondrial function. Three proton-translocating enzymes of the ETC, namely complexes I, III and IV, generate proton motive force, which in turn drives ATP synthase (complex V). The atomic structures and basic mechanisms of most respiratory complexes have previously been established, with the exception of complex I, the largest complex in the ETC. Recently, the crystal structure of the entire complex I was solved using a bacterial enzyme. The structure provided novel insights into the core architecture of the complex, the electron transfer and proton translocation pathways, as well as the mechanism that couples these two processes.
AU - Sazanov, Leonid A
ID - 1638
IS - 6
JF - Nature Reviews Molecular Cell Biology
TI - A giant molecular proton pump: structure and mechanism of respiratory complex I
VL - 16
ER -
TY - JOUR
AB - In this paper the optimal transport and the metamorphosis perspectives are combined. For a pair of given input images geodesic paths in the space of images are defined as minimizers of a resulting path energy. To this end, the underlying Riemannian metric measures the rate of transport cost and the rate of viscous dissipation. Furthermore, the model is capable to deal with strongly varying image contrast and explicitly allows for sources and sinks in the transport equations which are incorporated in the metric related to the metamorphosis approach by Trouvé and Younes. In the non-viscous case with source term existence of geodesic paths is proven in the space of measures. The proposed model is explored on the range from merely optimal transport to strongly dissipative dynamics. For this model a robust and effective variational time discretization of geodesic paths is proposed. This requires to minimize a discrete path energy consisting of a sum of consecutive image matching functionals. These functionals are defined on corresponding pairs of intensity functions and on associated pairwise matching deformations. Existence of time discrete geodesics is demonstrated. Furthermore, a finite element implementation is proposed and applied to instructive test cases and to real images. In the non-viscous case this is compared to the algorithm proposed by Benamou and Brenier including a discretization of the source term. Finally, the model is generalized to define discrete weighted barycentres with applications to textures and objects.
AU - Maas, Jan
AU - Rumpf, Martin
AU - Schönlieb, Carola
AU - Simon, Stefan
ID - 1639
IS - 6
JF - ESAIM: Mathematical Modelling and Numerical Analysis
TI - A generalized model for optimal transport of images including dissipation and density modulation
VL - 49
ER -
TY - JOUR
AB - Auxin and cytokinin are key endogenous regulators of plant development. Although cytokinin-mediated modulation of auxin distribution is a developmentally crucial hormonal interaction, its molecular basis is largely unknown. Here we show a direct regulatory link between cytokinin signalling and the auxin transport machinery uncovering a mechanistic framework for cytokinin-auxin cross-talk. We show that the CYTOKININ RESPONSE FACTORS (CRFs), transcription factors downstream of cytokinin perception, transcriptionally control genes encoding PIN-FORMED (PIN) auxin transporters at a specific PIN CYTOKININ RESPONSE ELEMENT (PCRE) domain. Removal of this cis-regulatory element effectively uncouples PIN transcription from the CRF-mediated cytokinin regulation and attenuates plant cytokinin sensitivity. We propose that CRFs represent a missing cross-talk component that fine-tunes auxin transport capacity downstream of cytokinin signalling to control plant development.
AU - Šimášková, Mária
AU - O'Brien, José
AU - Khan-Djamei, Mamoona
AU - Van Noorden, Giel
AU - Ötvös, Krisztina
AU - Vieten, Anne
AU - De Clercq, Inge
AU - Van Haperen, Johanna
AU - Cuesta, Candela
AU - Hoyerová, Klára
AU - Vanneste, Steffen
AU - Marhavy, Peter
AU - Wabnik, Krzysztof T
AU - Van Breusegem, Frank
AU - Nowack, Moritz
AU - Murphy, Angus
AU - Friml, Jiřĺ
AU - Weijers, Dolf
AU - Beeckman, Tom
AU - Benková, Eva
ID - 1640
JF - Nature Communications
TI - Cytokinin response factors regulate PIN-FORMED auxin transporters
VL - 6
ER -
TY - JOUR
AB - The Hanani-Tutte theorem is a classical result proved for the first time in the 1930s that characterizes planar graphs as graphs that admit a drawing in the plane in which every pair of edges not sharing a vertex cross an even number of times. We generalize this result to clustered graphs with two disjoint clusters, and show that a straightforward extension to flat clustered graphs with three or more disjoint clusters is not possible. For general clustered graphs we show a variant of the Hanani-Tutte theorem in the case when each cluster induces a connected subgraph. Di Battista and Frati proved that clustered planarity of embedded clustered graphs whose every face is incident to at most five vertices can be tested in polynomial time. We give a new and short proof of this result, using the matroid intersection algorithm.
AU - Fulek, Radoslav
AU - Kynčl, Jan
AU - Malinovič, Igor
AU - Pálvölgyi, Dömötör
ID - 1642
IS - 4
JF - Electronic Journal of Combinatorics
TI - Clustered planarity testing revisited
VL - 22
ER -
TY - CONF
AB - Increasing the computational complexity of evaluating a hash function, both for the honest users as well as for an adversary, is a useful technique employed for example in password-based cryptographic schemes to impede brute-force attacks, and also in so-called proofs of work (used in protocols like Bitcoin) to show that a certain amount of computation was performed by a legitimate user. A natural approach to adjust the complexity of a hash function is to iterate it c times, for some parameter c, in the hope that any query to the scheme requires c evaluations of the underlying hash function. However, results by Dodis et al. (Crypto 2012) imply that plain iteration falls short of achieving this goal, and designing schemes which provably have such a desirable property remained an open problem. This paper formalizes explicitly what it means for a given scheme to amplify the query complexity of a hash function. In the random oracle model, the goal of a secure query-complexity amplifier (QCA) scheme is captured as transforming, in the sense of indifferentiability, a random oracle allowing R queries (for the adversary) into one provably allowing only r < R queries. Turned around, this means that making r queries to the scheme requires at least R queries to the actual random oracle. Second, a new scheme, called collision-free iteration, is proposed and proven to achieve c-fold QCA for both the honest parties and the adversary, for any fixed parameter c.
AU - Demay, Grégory
AU - Gazi, Peter
AU - Maurer, Ueli
AU - Tackmann, Björn
ID - 1644
TI - Query-complexity amplification for random oracles
VL - 9063
ER -
TY - CONF
AB - Secret-key constructions are often proved secure in a model where one or more underlying components are replaced by an idealized oracle accessible to the attacker. This model gives rise to information-theoretic security analyses, and several advances have been made in this area over the last few years. This paper provides a systematic overview of what is achievable in this model, and how existing works fit into this view.
AU - Gazi, Peter
AU - Tessaro, Stefano
ID - 1645
T2 - 2015 IEEE Information Theory Workshop
TI - Secret-key cryptography from ideal primitives: A systematic verview
ER -
TY - CONF
AB - A pseudorandom function (PRF) is a keyed function F : K × X → Y where, for a random key k ∈ K, the function F(k, ·) is indistinguishable from a uniformly random function, given black-box access. A key-homomorphic PRF has the additional feature that for any keys k, k' and any input x, we have F(k+k', x) = F(k, x)⊕F(k', x) for some group operations +,⊕ on K and Y, respectively. A constrained PRF for a family of setsS ⊆ P(X) has the property that, given any key k and set S ∈ S, one can efficiently compute a “constrained” key kS that enables evaluation of F(k, x) on all inputs x ∈ S, while the values F(k, x) for x /∈ S remain pseudorandom even given kS. In this paper we construct PRFs that are simultaneously constrained and key homomorphic, where the homomorphic property holds even for constrained keys. We first show that the multilinear map-based bit-fixing and circuit-constrained PRFs of Boneh and Waters (Asiacrypt 2013) can be modified to also be keyhomomorphic. We then show that the LWE-based key-homomorphic PRFs of Banerjee and Peikert (Crypto 2014) are essentially already prefix-constrained PRFs, using a (non-obvious) definition of constrained keys and associated group operation. Moreover, the constrained keys themselves are pseudorandom, and the constraining and evaluation functions can all be computed in low depth. As an application of key-homomorphic constrained PRFs,we construct a proxy re-encryption schemewith fine-grained access control. This scheme allows storing encrypted data on an untrusted server, where each file can be encrypted relative to some attributes, so that only parties whose constrained keys match the attributes can decrypt. Moreover, the server can re-key (arbitrary subsets of) the ciphertexts without learning anything about the plaintexts, thus permitting efficient and finegrained revocation.
AU - Banerjee, Abishek
AU - Fuchsbauer, Georg
AU - Peikert, Chris
AU - Pietrzak, Krzysztof Z
AU - Stevens, Sophie
ID - 1646
TI - Key-homomorphic constrained pseudorandom functions
VL - 9015
ER -
TY - CONF
AB - Round-optimal blind signatures are notoriously hard to construct in the standard model, especially in the malicious-signer model, where blindness must hold under adversarially chosen keys. This is substantiated by several impossibility results. The only construction that can be termed theoretically efficient, by Garg and Gupta (Eurocrypt’14), requires complexity leveraging, inducing an exponential security loss. We present a construction of practically efficient round-optimal blind signatures in the standard model. It is conceptually simple and builds on the recent structure-preserving signatures on equivalence classes (SPSEQ) from Asiacrypt’14. While the traditional notion of blindness follows from standard assumptions, we prove blindness under adversarially chosen keys under an interactive variant of DDH. However, we neither require non-uniform assumptions nor complexity leveraging. We then show how to extend our construction to partially blind signatures and to blind signatures on message vectors, which yield a construction of one-show anonymous credentials à la “anonymous credentials light” (CCS’13) in the standard model. Furthermore, we give the first SPS-EQ construction under noninteractive assumptions and show how SPS-EQ schemes imply conventional structure-preserving signatures, which allows us to apply optimality results for the latter to SPS-EQ.
AU - Fuchsbauer, Georg
AU - Hanser, Christian
AU - Slamanig, Daniel
ID - 1647
TI - Practical round-optimal blind signatures in the standard model
VL - 9216
ER -
TY - CONF
AB - Generalized Selective Decryption (GSD), introduced by Panjwani [TCC’07], is a game for a symmetric encryption scheme Enc that captures the difficulty of proving adaptive security of certain protocols, most notably the Logical Key Hierarchy (LKH) multicast encryption protocol. In the GSD game there are n keys k1,..., kn, which the adversary may adaptively corrupt (learn); moreover, it can ask for encryptions Encki (kj) of keys under other keys. The adversary’s task is to distinguish keys (which it cannot trivially compute) from random. Proving the hardness of GSD assuming only IND-CPA security of Enc is surprisingly hard. Using “complexity leveraging” loses a factor exponential in n, which makes the proof practically meaningless. We can think of the GSD game as building a graph on n vertices, where we add an edge i → j when the adversary asks for an encryption of kj under ki. If restricted to graphs of depth ℓ, Panjwani gave a reduction that loses only a factor exponential in ℓ (not n). To date, this is the only non-trivial result known for GSD. In this paper we give almost-polynomial reductions for large classes of graphs. Most importantly, we prove the security of the GSD game restricted to trees losing only a quasi-polynomial factor n3 log n+5. Trees are an important special case capturing real-world protocols like the LKH protocol. Our new bound improves upon Panjwani’s on some LKH variants proposed in the literature where the underlying tree is not balanced. Our proof builds on ideas from the “nested hybrids” technique recently introduced by Fuchsbauer et al. [Asiacrypt’14] for proving the adaptive security of constrained PRFs.
AU - Fuchsbauer, Georg
AU - Jafargholi, Zahra
AU - Pietrzak, Krzysztof Z
ID - 1648
TI - A quasipolynomial reduction for generalized selective decryption on trees
VL - 9215
ER -
TY - CONF
AB - We extend a commitment scheme based on the learning with errors over rings (RLWE) problem, and present efficient companion zeroknowledge proofs of knowledge. Our scheme maps elements from the ring (or equivalently, n elements from
AU - Benhamouda, Fabrice
AU - Krenn, Stephan
AU - Lyubashevsky, Vadim
AU - Pietrzak, Krzysztof Z
ID - 1649
TI - Efficient zero-knowledge proofs for commitments from learning with errors over rings
VL - 9326
ER -
TY - CONF
AB - We consider the task of deriving a key with high HILL entropy (i.e., being computationally indistinguishable from a key with high min-entropy) from an unpredictable source.
Previous to this work, the only known way to transform unpredictability into a key that was ϵ indistinguishable from having min-entropy was via pseudorandomness, for example by Goldreich-Levin (GL) hardcore bits. This approach has the inherent limitation that from a source with k bits of unpredictability entropy one can derive a key of length (and thus HILL entropy) at most k−2log(1/ϵ) bits. In many settings, e.g. when dealing with biometric data, such a 2log(1/ϵ) bit entropy loss in not an option. Our main technical contribution is a theorem that states that in the high entropy regime, unpredictability implies HILL entropy. Concretely, any variable K with |K|−d bits of unpredictability entropy has the same amount of so called metric entropy (against real-valued, deterministic distinguishers), which is known to imply the same amount of HILL entropy. The loss in circuit size in this argument is exponential in the entropy gap d, and thus this result only applies for small d (i.e., where the size of distinguishers considered is exponential in d).
To overcome the above restriction, we investigate if it’s possible to first “condense” unpredictability entropy and make the entropy gap small. We show that any source with k bits of unpredictability can be condensed into a source of length k with k−3 bits of unpredictability entropy. Our condenser simply “abuses" the GL construction and derives a k bit key from a source with k bits of unpredicatibily. The original GL theorem implies nothing when extracting that many bits, but we show that in this regime, GL still behaves like a “condenser" for unpredictability. This result comes with two caveats (1) the loss in circuit size is exponential in k and (2) we require that the source we start with has no HILL entropy (equivalently, one can efficiently check if a guess is correct). We leave it as an intriguing open problem to overcome these restrictions or to prove they’re inherent.
AU - Skórski, Maciej
AU - Golovnev, Alexander
AU - Pietrzak, Krzysztof Z
ID - 1650
TI - Condensed unpredictability
VL - 9134
ER -
TY - CONF
AB - Cryptographic e-cash allows off-line electronic transactions between a bank, users and merchants in a secure and anonymous fashion. A plethora of e-cash constructions has been proposed in the literature; however, these traditional e-cash schemes only allow coins to be transferred once between users and merchants. Ideally, we would like users to be able to transfer coins between each other multiple times before deposit, as happens with physical cash. “Transferable” e-cash schemes are the solution to this problem. Unfortunately, the currently proposed schemes are either completely impractical or do not achieve the desirable anonymity properties without compromises, such as assuming the existence of a trusted “judge” who can trace all coins and users in the system. This paper presents the first efficient and fully anonymous transferable e-cash scheme without any trusted third parties. We start by revising the security and anonymity properties of transferable e-cash to capture issues that were previously overlooked. For our construction we use the recently proposed malleable signatures by Chase et al. to allow the secure and anonymous transfer of coins, combined with a new efficient double-spending detection mechanism. Finally, we discuss an instantiation of our construction.
AU - Baldimtsi, Foteini
AU - Chase, Melissa
AU - Fuchsbauer, Georg
AU - Kohlweiss, Markulf
ID - 1651
TI - Anonymous transferable e-cash
VL - 9020
ER -
TY - CONF
AB - We develop new theoretical tools for proving lower-bounds on the (amortized) complexity of certain functions in models of parallel computation. We apply the tools to construct a class of functions with high amortized memory complexity in the parallel Random Oracle Model (pROM); a variant of the standard ROM allowing for batches of simultaneous queries. In particular we obtain a new, more robust, type of Memory-Hard Functions (MHF); a security primitive which has recently been gaining acceptance in practice as an effective means of countering brute-force attacks on security relevant functions. Along the way we also demonstrate an important shortcoming of previous definitions of MHFs and give a new definition addressing the problem. The tools we develop represent an adaptation of the powerful pebbling paradigm (initially introduced by Hewitt and Paterson [HP70] and Cook [Coo73]) to a simple and intuitive parallel setting. We define a simple pebbling game Gp over graphs which aims to abstract parallel computation in an intuitive way. As a conceptual contribution we define a measure of pebbling complexity for graphs called cumulative complexity (CC) and show how it overcomes a crucial shortcoming (in the parallel setting) exhibited by more traditional complexity measures used in the past. As a main technical contribution we give an explicit construction of a constant in-degree family of graphs whose CC in Gp approaches maximality to within a polylogarithmic factor for any graph of equal size (analogous to the graphs of Tarjan et. al. [PTC76, LT82] for sequential pebbling games). Finally, for a given graph G and related function fG, we derive a lower-bound on the amortized memory complexity of fG in the pROM in terms of the CC of G in the game Gp.
AU - Alwen, Joel F
AU - Serbinenko, Vladimir
ID - 1652
T2 - Proceedings of the 47th annual ACM symposium on Theory of computing
TI - High parallel complexity graphs and memory-hard functions
ER -
TY - CONF
AB - HMAC and its variant NMAC are the most popular approaches to deriving a MAC (and more generally, a PRF) from a cryptographic hash function. Despite nearly two decades of research, their exact security still remains far from understood in many different contexts. Indeed, recent works have re-surfaced interest for {\em generic} attacks, i.e., attacks that treat the compression function of the underlying hash function as a black box.
Generic security can be proved in a model where the underlying compression function is modeled as a random function -- yet, to date, the question of proving tight, non-trivial bounds on the generic security of HMAC/NMAC even as a PRF remains a challenging open question.
In this paper, we ask the question of whether a small modification to HMAC and NMAC can allow us to exactly characterize the security of the resulting constructions, while only incurring little penalty with respect to efficiency. To this end, we present simple variants of NMAC and HMAC, for which we prove tight bounds on the generic PRF security, expressed in terms of numbers of construction and compression function queries necessary to break the construction. All of our constructions are obtained via a (near) {\em black-box} modification of NMAC and HMAC, which can be interpreted as an initial step of key-dependent message pre-processing.
While our focus is on PRF security, a further attractive feature of our new constructions is that they clearly defeat all recent generic attacks against properties such as state recovery and universal forgery. These exploit properties of the so-called ``functional graph'' which are not directly accessible in our new constructions.
AU - Gazi, Peter
AU - Pietrzak, Krzysztof Z
AU - Tessaro, Stefano
ID - 1654
TI - Generic security of NMAC and HMAC with input whitening
VL - 9453
ER -
TY - JOUR
AB - Quantifying behaviors of robots which were generated autonomously from task-independent objective functions is an important prerequisite for objective comparisons of algorithms and movements of animals. The temporal sequence of such a behavior can be considered as a time series and hence complexity measures developed for time series are natural candidates for its quantification. The predictive information and the excess entropy are such complexity measures. They measure the amount of information the past contains about the future and thus quantify the nonrandom structure in the temporal sequence. However, when using these measures for systems with continuous states one has to deal with the fact that their values will depend on the resolution with which the systems states are observed. For deterministic systems both measures will diverge with increasing resolution. We therefore propose a new decomposition of the excess entropy in resolution dependent and resolution independent parts and discuss how they depend on the dimensionality of the dynamics, correlations and the noise level. For the practical estimation we propose to use estimates based on the correlation integral instead of the direct estimation of the mutual information based on next neighbor statistics because the latter allows less control of the scale dependencies. Using our algorithm we are able to show how autonomous learning generates behavior of increasing complexity with increasing learning duration.
AU - Martius, Georg S
AU - Olbrich, Eckehard
ID - 1655
IS - 10
JF - Entropy
TI - Quantifying emergent behavior of autonomous robots
VL - 17
ER -
TY - CONF
AB - Recently there has been a significant effort to handle quantitative properties in formal verification and synthesis. While weighted automata over finite and infinite words provide a natural and flexible framework to express quantitative properties, perhaps surprisingly, some basic system properties such as average response time cannot be expressed using weighted automata, nor in any other know decidable formalism. In this work, we introduce nested weighted automata as a natural extension of weighted automata which makes it possible to express important quantitative properties such as average response time. In nested weighted automata, a master automaton spins off and collects results from weighted slave automata, each of which computes a quantity along a finite portion of an infinite word. Nested weighted automata can be viewed as the quantitative analogue of monitor automata, which are used in run-time verification. We establish an almost complete decidability picture for the basic decision problems about nested weighted automata, and illustrate their applicability in several domains. In particular, nested weighted automata can be used to decide average response time properties.
AU - Chatterjee, Krishnendu
AU - Henzinger, Thomas A
AU - Otop, Jan
ID - 1656
T2 - Proceedings - Symposium on Logic in Computer Science
TI - Nested weighted automata
VL - 2015-July
ER -
TY - CONF
AB - We consider Markov decision processes (MDPs) with multiple limit-average (or mean-payoff) objectives. There exist two different views: (i) ~the expectation semantics, where the goal is to optimize the expected mean-payoff objective, and (ii) ~the satisfaction semantics, where the goal is to maximize the probability of runs such that the mean-payoff value stays above a given vector. We consider optimization with respect to both objectives at once, thus unifying the existing semantics. Precisely, the goal is to optimize the expectation while ensuring the satisfaction constraint. Our problem captures the notion of optimization with respect to strategies that are risk-averse (i.e., Ensure certain probabilistic guarantee). Our main results are as follows: First, we present algorithms for the decision problems, which are always polynomial in the size of the MDP. We also show that an approximation of the Pareto curve can be computed in time polynomial in the size of the MDP, and the approximation factor, but exponential in the number of dimensions. Second, we present a complete characterization of the strategy complexity (in terms of memory bounds and randomization) required to solve our problem.
AU - Chatterjee, Krishnendu
AU - Komárková, Zuzana
AU - Kretinsky, Jan
ID - 1657
TI - Unifying two views on multiple mean-payoff objectives in Markov decision processes
ER -
TY - CONF
AB - Continuous-time Markov chain (CTMC) models have become a central tool for understanding the dynamics of complex reaction networks and the importance of stochasticity in the underlying biochemical processes. When such models are employed to answer questions in applications, in order to ensure that the model provides a sufficiently accurate representation of the real system, it is of vital importance that the model parameters are inferred from real measured data. This, however, is often a formidable task and all of the existing methods fail in one case or the other, usually because the underlying CTMC model is high-dimensional and computationally difficult to analyze. The parameter inference methods that tend to scale best in the dimension of the CTMC are based on so-called moment closure approximations. However, there exists a large number of different moment closure approximations and it is typically hard to say a priori which of the approximations is the most suitable for the inference procedure. Here, we propose a moment-based parameter inference method that automatically chooses the most appropriate moment closure method. Accordingly, contrary to existing methods, the user is not required to be experienced in moment closure techniques. In addition to that, our method adaptively changes the approximation during the parameter inference to ensure that always the best approximation is used, even in cases where different approximations are best in different regions of the parameter space.
AU - Bogomolov, Sergiy
AU - Henzinger, Thomas A
AU - Podelski, Andreas
AU - Ruess, Jakob
AU - Schilling, Christian
ID - 1658
TI - Adaptive moment closure for parameter inference of biochemical reaction networks
VL - 9308
ER -
TY - CONF
AB - The target discounted-sum problem is the following: Given a rational discount factor 0 < λ < 1 and three rational values a, b, and t, does there exist a finite or an infinite sequence w ε(a, b)∗ or w ε(a, b)w, such that Σ|w| i=0 w(i)λi equals t? The problem turns out to relate to many fields of mathematics and computer science, and its decidability question is surprisingly hard to solve. We solve the finite version of the problem, and show the hardness of the infinite version, linking it to various areas and open problems in mathematics and computer science: β-expansions, discounted-sum automata, piecewise affine maps, and generalizations of the Cantor set. We provide some partial results to the infinite version, among which are solutions to its restriction to eventually-periodic sequences and to the cases that λ λ 1/2 or λ = 1/n, for every n ε N. We use our results for solving some open problems on discounted-sum automata, among which are the exact-value problem for nondeterministic automata over finite words and the universality and inclusion problems for functional automata.
AU - Boker, Udi
AU - Henzinger, Thomas A
AU - Otop, Jan
ID - 1659
SN - 1043-6871
T2 - LICS
TI - The target discounted-sum problem
ER -
TY - CONF
AB - We study the pattern frequency vector for runs in probabilistic Vector Addition Systems with States (pVASS). Intuitively, each configuration of a given pVASS is assigned one of finitely many patterns, and every run can thus be seen as an infinite sequence of these patterns. The pattern frequency vector assigns to each run the limit of pattern frequencies computed for longer and longer prefixes of the run. If the limit does not exist, then the vector is undefined. We show that for one-counter pVASS, the pattern frequency vector is defined and takes one of finitely many values for almost all runs. Further, these values and their associated probabilities can be approximated up to an arbitrarily small relative error in polynomial time. For stable two-counter pVASS, we show the same result, but we do not provide any upper complexity bound. As a byproduct of our study, we discover counterexamples falsifying some classical results about stochastic Petri nets published in the 80s.
AU - Brázdil, Tomáš
AU - Kiefer, Stefan
AU - Kučera, Antonín
AU - Novotny, Petr
ID - 1660
TI - Long-run average behaviour of probabilistic vector addition systems
ER -
TY - CONF
AB - The computation of the winning set for one-pair Streett objectives and for k-pair Streett objectives in (standard) 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-formed ness of specifications, and the synthesis of reactive systems. We give faster algorithms for the computation of the winning set for (1) one-pair Streett objectives (aka parity-3 problem) in game graphs and (2) for k-pair Streett objectives in graphs. For both problems this represents the first improvement in asymptotic running time in 15 years.
AU - Chatterjee, Krishnendu
AU - Henzinger, Monika
AU - Loitzenbauer, Veronika
ID - 1661
T2 - Proceedings - Symposium on Logic in Computer Science
TI - Improved algorithms for one-pair and k-pair Streett objectives
VL - 2015-July
ER -
TY - JOUR
AB - CREB-binding protein (CBP) and p300 are transcriptional coactivators involved in numerous biological processes that affect cell growth, transformation, differentiation, and development. In this study, we provide evidence of the involvement of homeodomain-interacting protein kinase 2 (HIPK2) in the regulation of CBP activity. We show that HIPK2 interacts with and phosphorylates several regions of CBP. We demonstrate that serines 2361, 2363, 2371, 2376, and 2381 are responsible for the HIPK2-induced mobility shift of CBP C-terminal activation domain. Moreover, we show that HIPK2 strongly potentiates the transcriptional activity of CBP. However, our data suggest that HIPK2 activates CBP mainly by counteracting the repressive action of cell cycle regulatory domain 1 (CRD1), located between amino acids 977 and 1076, independently of CBP phosphorylation. Our findings thus highlight a complex regulation of CBP activity by HIPK2, which might be relevant for the control of specific sets of target genes involved in cellular proliferation, differentiation and apoptosis.
AU - Kovács, Krisztián
AU - Steinmann, Myriam
AU - Halfon, Olivier
AU - Magistretti, Pierre
AU - Cardinaux, Jean
ID - 1663
IS - 11
JF - Cellular Signalling
TI - Complex regulation of CREB-binding protein by homeodomain-interacting protein kinase 2
VL - 27
ER -
TY - JOUR
AB - Over a century of research into the origin of turbulence in wall-bounded shear flows has resulted in a puzzling picture in which turbulence appears in a variety of different states competing with laminar background flow. At moderate flow speeds, turbulence is confined to localized patches; it is only at higher speeds that the entire flow becomes turbulent. The origin of the different states encountered during this transition, the front dynamics of the turbulent regions and the transformation to full turbulence have yet to be explained. By combining experiments, theory and computer simulations, here we uncover a bifurcation scenario that explains the transformation to fully turbulent pipe flow and describe the front dynamics of the different states encountered in the process. Key to resolving this problem is the interpretation of the flow as a bistable system with nonlinear propagation (advection) of turbulent fronts. These findings bridge the gap between our understanding of the onset of turbulence and fully turbulent flows.
AU - Barkley, Dwight
AU - Song, Baofang
AU - Vasudevan, Mukund
AU - Lemoult, Grégoire M
AU - Avila, Marc
AU - Hof, Björn
ID - 1664
IS - 7574
JF - Nature
TI - The rise of fully turbulent flow
VL - 526
ER -
TY - JOUR
AB - Which genetic alterations drive tumorigenesis and how they evolve over the course of disease and therapy are central questions in cancer biology. Here we identify 44 recurrently mutated genes and 11 recurrent somatic copy number variations through whole-exome sequencing of 538 chronic lymphocytic leukaemia (CLL) and matched germline DNA samples, 278 of which were collected in a prospective clinical trial. These include previously unrecognized putative cancer drivers (RPS15, IKZF3), and collectively identify RNA processing and export, MYC activity, and MAPK signalling as central pathways involved in CLL. Clonality analysis of this large data set further enabled reconstruction of temporal relationships between driver events. Direct comparison between matched pre-treatment and relapse samples from 59 patients demonstrated highly frequent clonal evolution. Thus, large sequencing data sets of clinically informative samples enable the discovery of novel genes associated with cancer, the network of relationships between the driver events, and their impact on disease relapse and clinical outcome.
AU - Landau, Dan
AU - Tausch, Eugen
AU - Taylor Weiner, Amaro
AU - Stewart, Chip
AU - Reiter, Johannes
AU - Bahlo, Jasmin
AU - Kluth, Sandra
AU - Božić, Ivana
AU - Lawrence, Michael
AU - Böttcher, Sebastian
AU - Carter, Scott
AU - Cibulskis, Kristian
AU - Mertens, Daniel
AU - Sougnez, Carrie
AU - Rosenberg, Mara
AU - Hess, Julian
AU - Edelmann, Jennifer
AU - Kless, Sabrina
AU - Kneba, Michael
AU - Ritgen, Matthias
AU - Fink, Anna
AU - Fischer, Kirsten
AU - Gabriel, Stacey
AU - Lander, Eric
AU - Nowak, Martin
AU - Döhner, Hartmut
AU - Hallek, Michael
AU - Neuberg, Donna
AU - Getz, Gad
AU - Stilgenbauer, Stephan
AU - Wu, Catherine
ID - 1665
IS - 7574
JF - Nature
TI - Mutations driving CLL and their evolution in progression and relapse
VL - 526
ER -
TY - CONF
AB - We consider parametric version of fixed-delay continuoustime Markov chains (or equivalently deterministic and stochastic Petri nets, DSPN) where fixed-delay transitions are specified by parameters, rather than concrete values. Our goal is to synthesize values of these parameters that, for a given cost function, minimise expected total cost incurred before reaching a given set of target states. We show that under mild assumptions, optimal values of parameters can be effectively approximated using translation to a Markov decision process (MDP) whose actions correspond to discretized values of these parameters. To this end we identify and overcome several interesting phenomena arising in systems with fixed delays.
AU - Brázdil, Tomáš
AU - Korenčiak, L'Uboš
AU - Krčál, Jan
AU - Novotny, Petr
AU - Řehák, Vojtěch
ID - 1667
TI - Optimizing performance of continuous-time stochastic systems using timeout synthesis
VL - 9259
ER -
TY - CONF
AB - We revisit the security (as a pseudorandom permutation) of cascading-based constructions for block-cipher key-length extension. Previous works typically considered the extreme case where the adversary is given the entire codebook of the construction, the only complexity measure being the number qe of queries to the underlying ideal block cipher, representing adversary’s secret-key-independent computation. Here, we initiate a systematic study of the more natural case of an adversary restricted to adaptively learning a number qc of plaintext/ciphertext pairs that is less than the entire codebook. For any such qc, we aim to determine the highest number of block-cipher queries qe the adversary can issue without being able to successfully distinguish the construction (under a secret key) from a random permutation.
More concretely, we show the following results for key-length extension schemes using a block cipher with n-bit blocks and κ-bit keys:
Plain cascades of length ℓ=2r+1 are secure whenever qcqre≪2r(κ+n), qc≪2κ and qe≪22κ. The bound for r=1 also applies to two-key triple encryption (as used within Triple DES).
The r-round XOR-cascade is secure as long as qcqre≪2r(κ+n), matching an attack by Gaži (CRYPTO 2013).
We fully characterize the security of Gaži and Tessaro’s two-call
AU - Gazi, Peter
AU - Lee, Jooyoung
AU - Seurin, Yannick
AU - Steinberger, John
AU - Tessaro, Stefano
ID - 1668
TI - Relaxing full-codebook security: A refined analysis of key-length extension schemes
VL - 9054
ER -
TY - CONF
AB - Computational notions of entropy (a.k.a. pseudoentropy) have found many applications, including leakage-resilient cryptography, deterministic encryption or memory delegation. The most important tools to argue about pseudoentropy are chain rules, which quantify by how much (in terms of quantity and quality) the pseudoentropy of a given random variable X decreases when conditioned on some other variable Z (think for example of X as a secret key and Z as information leaked by a side-channel). In this paper we give a very simple and modular proof of the chain rule for HILL pseudoentropy, improving best known parameters. Our version allows for increasing the acceptable length of leakage in applications up to a constant factor compared to the best previous bounds. As a contribution of independent interest, we provide a comprehensive study of all known versions of the chain rule, comparing their worst-case strength and limitations.
AU - Pietrzak, Krzysztof Z
AU - Skórski, Maciej
ID - 1669
TI - The chain rule for HILL pseudoentropy, revisited
VL - 9230
ER -
TY - CONF
AB - Planning in hybrid domains poses a special challenge due to the involved mixed discrete-continuous dynamics. A recent solving approach for such domains is based on applying model checking techniques on a translation of PDDL+ planning problems to hybrid automata. However, the proposed translation is limited because must behavior is only overapproximated, and hence, processes and events are not reflected exactly. In this paper, we present the theoretical foundation of an exact PDDL+ translation. We propose a schema to convert a hybrid automaton with must transitions into an equivalent hybrid automaton featuring only may transitions.
AU - Bogomolov, Sergiy
AU - Magazzeni, Daniele
AU - Minopoli, Stefano
AU - Wehrle, Martin
ID - 1670
TI - PDDL+ planning with hybrid automata: Foundations of translating must behavior
ER -
TY - CONF
AB - This paper studies the concrete security of PRFs and MACs obtained by keying hash functions based on the sponge paradigm. One such hash function is KECCAK, selected as NIST’s new SHA-3 standard. In contrast to other approaches like HMAC, the exact security of keyed sponges is not well understood. Indeed, recent security analyses delivered concrete security bounds which are far from existing attacks. This paper aims to close this gap. We prove (nearly) exact bounds on the concrete PRF security of keyed sponges using a random permutation. These bounds are tight for the most relevant ranges of parameters, i.e., for messages of length (roughly) l ≤ min{2n/4, 2r} blocks, where n is the state size and r is the desired output length; and for l ≤ q queries (to the construction or the underlying permutation). Moreover, we also improve standard-model bounds. As an intermediate step of independent interest, we prove tight bounds on the PRF security of the truncated CBC-MAC construction, which operates as plain CBC-MAC, but only returns a prefix of the output.
AU - Gazi, Peter
AU - Pietrzak, Krzysztof Z
AU - Tessaro, Stefano
ID - 1671
TI - The exact PRF security of truncation: Tight bounds for keyed sponges and truncated CBC
VL - 9215
ER -
TY - CONF
AB - Composable notions of incoercibility aim to forbid a coercer from using anything beyond the coerced parties’ inputs and outputs to catch them when they try to deceive him. Existing definitions are restricted to weak coercion types, and/or are not universally composable. Furthermore, they often make too strong assumptions on the knowledge of coerced parties—e.g., they assume they known the identities and/or the strategies of other coerced parties, or those of corrupted parties— which makes them unsuitable for applications of incoercibility such as e-voting, where colluding adversarial parties may attempt to coerce honest voters, e.g., by offering them money for a promised vote, and use their own view to check that the voter keeps his end of the bargain. In this work we put forward the first universally composable notion of incoercible multi-party computation, which satisfies the above intuition and does not assume collusions among coerced parties or knowledge of the corrupted set. We define natural notions of UC incoercibility corresponding to standard coercion-types, i.e., receipt-freeness and resistance to full-active coercion. Importantly, our suggested notion has the unique property that it builds on top of the well studied UC framework by Canetti instead of modifying it. This guarantees backwards compatibility, and allows us to inherit results from the rich UC literature. We then present MPC protocols which realize our notions of UC incoercibility given access to an arguably minimal setup—namely honestly generate tamper-proof hardware performing a very simple cryptographic operation—e.g., a smart card. This is, to our knowledge, the first proposed construction of an MPC protocol (for more than two parties) that is incoercibly secure and universally composable, and therefore the first construction of a universally composable receipt-free e-voting protocol.
AU - Alwen, Joel F
AU - Ostrovsky, Rafail
AU - Zhou, Hongsheng
AU - Zikas, Vassilis
ID - 1672
TI - Incoercible multi-party computation and universally composable receipt-free voting
VL - 9216
ER -
TY - JOUR
AB - When a new mutant arises in a population, there is a probability it outcompetes the residents and fixes. The structure of the population can affect this fixation probability. Suppressing population structures reduce the difference between two competing variants, while amplifying population structures enhance the difference. Suppressors are ubiquitous and easy to construct, but amplifiers for the large population limit are more elusive and only a few examples have been discovered. Whether or not a population structure is an amplifier of selection depends on the probability distribution for the placement of the invading mutant. First, we prove that there exist only bounded amplifiers for adversarial placement-that is, for arbitrary initial conditions. Next, we show that the Star population structure, which is known to amplify for mutants placed uniformly at random, does not amplify for mutants that arise through reproduction and are therefore placed proportional to the temperatures of the vertices. Finally, we construct population structures that amplify for all mutational events that arise through reproduction, uniformly at random, or through some combination of the two.
AU - Adlam, Ben
AU - Chatterjee, Krishnendu
AU - Nowak, Martin
ID - 1673
IS - 2181
JF - Proceedings of the Royal Society A: Mathematical, Physical and Engineering Sciences
TI - Amplifiers of selection
VL - 471
ER -
TY - JOUR
AB - We consider N × N random matrices of the form H = W + V where W is a real symmetric Wigner matrix and V a random or deterministic, real, diagonal matrix whose entries are independent of W. We assume subexponential decay for the matrix entries of W and we choose V so that the eigenvalues of W and V are typically of the same order. For a large class of diagonal matrices V, we show that the rescaled distribution of the extremal eigenvalues is given by the Tracy-Widom distribution F1 in the limit of large N. Our proofs also apply to the complex Hermitian setting, i.e. when W is a complex Hermitian Wigner matrix.
AU - Lee, Jioon
AU - Schnelli, Kevin
ID - 1674
IS - 8
JF - Reviews in Mathematical Physics
TI - Edge universality for deformed Wigner matrices
VL - 27
ER -
TY - CONF
AB - Proofs of work (PoW) have been suggested by Dwork and Naor (Crypto’92) as protection to a shared resource. The basic idea is to ask the service requestor to dedicate some non-trivial amount of computational work to every request. The original applications included prevention of spam and protection against denial of service attacks. More recently, PoWs have been used to prevent double spending in the Bitcoin digital currency system. In this work, we put forward an alternative concept for PoWs - so-called proofs of space (PoS), where a service requestor must dedicate a significant amount of disk space as opposed to computation. We construct secure PoS schemes in the random oracle model (with one additional mild assumption required for the proof to go through), using graphs with high “pebbling complexity” and Merkle hash-trees. We discuss some applications, including follow-up work where a decentralized digital currency scheme called Spacecoin is constructed that uses PoS (instead of wasteful PoW like in Bitcoin) to prevent double spending. The main technical contribution of this work is the construction of (directed, loop-free) graphs on N vertices with in-degree O(log logN) such that even if one places Θ(N) pebbles on the nodes of the graph, there’s a constant fraction of nodes that needs Θ(N) steps to be pebbled (where in every step one can put a pebble on a node if all its parents have a pebble).
AU - Dziembowski, Stefan
AU - Faust, Sebastian
AU - Kolmogorov, Vladimir
AU - Pietrzak, Krzysztof Z
ID - 1675
TI - Proofs of space
VL - 9216
ER -
TY - JOUR
AU - Sixt, Michael K
AU - Raz, Erez
ID - 1676
IS - 10
JF - Current Opinion in Cell Biology
TI - Editorial overview: Cell adhesion and migration
VL - 36
ER -
TY - JOUR
AB - We consider real symmetric and complex Hermitian random matrices with the additional symmetry hxy = hN-y,N-x. The matrix elements are independent (up to the fourfold symmetry) and not necessarily identically distributed. This ensemble naturally arises as the Fourier transform of a Gaussian orthogonal ensemble. Italso occurs as the flip matrix model - an approximation of the two-dimensional Anderson model at small disorder. We show that the density of states converges to the Wigner semicircle law despite the new symmetry type. We also prove the local version of the semicircle law on the optimal scale.
AU - Alt, Johannes
ID - 1677
IS - 10
JF - Journal of Mathematical Physics
TI - The local semicircle law for random matrices with a fourfold symmetry
VL - 56
ER -
TY - JOUR
AB - High-throughput live-cell screens are intricate elements of systems biology studies and drug discovery pipelines. Here, we demonstrate an optogenetics-assisted method that avoids the need for chemical activators and reporters, reduces the number of operational steps and increases information content in a cell-based small-molecule screen against human protein kinases, including an orphan receptor tyrosine kinase. This blueprint for all-optical screening can be adapted to many drug targets and cellular processes.
AU - Inglés Prieto, Álvaro
AU - Gschaider-Reichhart, Eva
AU - Muellner, Markus
AU - Nowak, Matthias
AU - Nijman, Sebastian
AU - Grusch, Michael
AU - Janovjak, Harald L
ID - 1678
IS - 12
JF - Nature Chemical Biology
TI - Light-assisted small-molecule screening against protein kinases
VL - 11
ER -
TY - JOUR
AU - Lemoult, Grégoire M
AU - Maier, Philipp
AU - Hof, Björn
ID - 1679
IS - 9
JF - Physics of Fluids
TI - Taylor's Forest
VL - 27
ER -
TY - JOUR
AB - We consider the satisfiability problem for modal logic over first-order definable classes of frames.We confirm the conjecture from Hemaspaandra and Schnoor [2008] that modal logic is decidable over classes definable by universal Horn formulae. We provide a full classification of Horn formulae with respect to the complexity of the corresponding satisfiability problem. It turns out, that except for the trivial case of inconsistent formulae, local satisfiability is eitherNP-complete or PSPACE-complete, and global satisfiability is NP-complete, PSPACE-complete, or ExpTime-complete. We also show that the finite satisfiability problem for modal logic over Horn definable classes of frames is decidable. On the negative side, we show undecidability of two related problems. First, we exhibit a simple universal three-variable formula defining the class of frames over which modal logic is undecidable. Second, we consider the satisfiability problem of bimodal logic over Horn definable classes of frames, and also present a formula leading to undecidability.
AU - Michaliszyn, Jakub
AU - Otop, Jan
AU - Kieroňski, Emanuel
ID - 1680
IS - 1
JF - ACM Transactions on Computational Logic
TI - On the decidability of elementary modal logics
VL - 17
ER -
TY - JOUR
AB - In many social situations, individuals endeavor to find the single best possible partner, but are constrained to evaluate the candidates in sequence. Examples include the search for mates, economic partnerships, or any other long-term ties where the choice to interact involves two parties. Surprisingly, however, previous theoretical work on mutual choice problems focuses on finding equilibrium solutions, while ignoring the evolutionary dynamics of decisions. Empirically, this may be of high importance, as some equilibrium solutions can never be reached unless the population undergoes radical changes and a sufficient number of individuals change their decisions simultaneously. To address this question, we apply a mutual choice sequential search problem in an evolutionary game-theoretical model that allows one to find solutions that are favored by evolution. As an example, we study the influence of sequential search on the evolutionary dynamics of cooperation. For this, we focus on the classic snowdrift game and the prisoner’s dilemma game.
AU - Priklopil, Tadeas
AU - Chatterjee, Krishnendu
ID - 1681
IS - 4
JF - Games
TI - Evolution of decisions in population games with sequentially searching individuals
VL - 6
ER -
TY - JOUR
AB - We study the problem of robust satisfiability of systems of nonlinear equations, namely, whether for a given continuous function f:K→ ℝn on a finite simplicial complex K and α > 0, it holds that each function g: K → ℝn such that ||g - f || ∞ < α, has a root in K. Via a reduction to the extension problem of maps into a sphere, we particularly show that this problem is decidable in polynomial time for every fixed n, assuming dimK ≤ 2n - 3. This is a substantial extension of previous computational applications of topological degree and related concepts in numerical and interval analysis. Via a reverse reduction, we prove that the problem is undecidable when dim K > 2n - 2, where the threshold comes from the stable range in homotopy theory. For the lucidity of our exposition, we focus on the setting when f is simplexwise linear. Such functions can approximate general continuous functions, and thus we get approximation schemes and undecidability of the robust satisfiability in other possible settings.
AU - Franek, Peter
AU - Krcál, Marek
ID - 1682
IS - 4
JF - Journal of the ACM
TI - Robust satisfiability of systems of equations
VL - 62
ER -
TY - JOUR
AB - The 1 MDa, 45-subunit proton-pumping NADH-ubiquinone oxidoreductase (complex I) is the largest complex of the mitochondrial electron transport chain. The molecular mechanism of complex I is central to the metabolism of cells, but has yet to be fully characterized. The last two years have seen steady progress towards this goal with the first atomic-resolution structure of the entire bacterial complex I, a 5 Å cryo-electron microscopy map of bovine mitochondrial complex I and a ∼3.8 Å resolution X-ray crystallographic study of mitochondrial complex I from yeast Yarrowia lipotytica. In this review we will discuss what we have learned from these studies and what remains to be elucidated.
AU - Letts, Jame A
AU - Sazanov, Leonid A
ID - 1683
IS - 8
JF - Current Opinion in Structural Biology
TI - Gaining mass: The structure of respiratory complex I-from bacterial towards mitochondrial versions
VL - 33
ER -
TY - CONF
AB - Given a graph G cellularly embedded on a surface Σ of genus g, a cut graph is a subgraph of G such that cutting Σ along G yields a topological disk. We provide a fixed parameter tractable approximation scheme for the problem of computing the shortest cut graph, that is, for any ε > 0, we show how to compute a (1 + ε) approximation of the shortest cut graph in time f(ε, g)n3.
Our techniques first rely on the computation of a spanner for the problem using the technique of brick decompositions, to reduce the problem to the case of bounded tree-width. Then, to solve the bounded tree-width case, we introduce a variant of the surface-cut decomposition of Rué, Sau and Thilikos, which may be of independent interest.
AU - Cohen Addad, Vincent
AU - De Mesmay, Arnaud N
ID - 1685
TI - A fixed parameter tractable approximation scheme for the optimal cut graph of a surface
VL - 9294
ER -
TY - THES
AB - The human ability to recognize objects in complex scenes has driven research in the computer vision field over couple of decades. This thesis focuses on the object recognition task in images. That is, given the image, we want the computer system to be able to predict the class of the object that appears in the image. A recent succesful attempt to bridge semantic understanding of the image perceived by humans and by computers uses attribute-based models. Attributes are semantic properties of the objects shared across different categories, which humans and computers can decide on. To explore the attribute-based models we take a statistical machine learning approach, and address two key learning challenges in view of object recognition task: learning augmented attributes as mid-level discriminative feature representation, and learning with attributes as privileged information. Our main contributions are parametric and non-parametric models and algorithms to solve these frameworks. In the parametric approach, we explore an autoencoder model combined with the large margin nearest neighbor principle for mid-level feature learning, and linear support vector machines for learning with privileged information. In the non-parametric approach, we propose a supervised Indian Buffet Process for automatic augmentation of semantic attributes, and explore the Gaussian Processes classification framework for learning with privileged information. A thorough experimental analysis shows the effectiveness of the proposed models in both parametric and non-parametric views.
AU - Sharmanska, Viktoriia
ID - 1401
TI - Learning with attributes for object recognition: Parametric and non-parametrics views
ER -
TY - CONF
AB - We present a computer-aided programming approach to concurrency. The approach allows programmers to program assuming a friendly, non-preemptive scheduler, and our synthesis procedure inserts synchronization to ensure that the final program works even with a preemptive scheduler. The correctness specification is implicit, inferred from the non-preemptive behavior. Let us consider sequences of calls that the program makes to an external interface. The specification requires that any such sequence produced under a preemptive scheduler should be included in the set of such sequences produced under a non-preemptive scheduler. The solution is based on a finitary abstraction, an algorithm for bounded language inclusion modulo an independence relation, and rules for inserting synchronization. We apply the approach to device-driver programming, where the driver threads call the software interface of the device and the API provided by the operating system. Our experiments demonstrate that our synthesis method is precise and efficient, and, since it does not require explicit specifications, is more practical than the conventional approach based on user-provided assertions.
AU - Cerny, Pavol
AU - Clarke, Edmund
AU - Henzinger, Thomas A
AU - Radhakrishna, Arjun
AU - Ryzhyk, Leonid
AU - Samanta, Roopsha
AU - Tarrach, Thorsten
ID - 1729
TI - From non-preemptive to preemptive scheduling using synchronization synthesis
VL - 9207
ER -
TY - JOUR
AB - Evolution of gene regulation is crucial for our understanding of the phenotypic differences between species, populations and individuals. Sequence-specific binding of transcription factors to the regulatory regions on the DNA is a key regulatory mechanism that determines gene expression and hence heritable phenotypic variation. We use a biophysical model for directional selection on gene expression to estimate the rates of gain and loss of transcription factor binding sites (TFBS) in finite populations under both point and insertion/deletion mutations. Our results show that these rates are typically slow for a single TFBS in an isolated DNA region, unless the selection is extremely strong. These rates decrease drastically with increasing TFBS length or increasingly specific protein-DNA interactions, making the evolution of sites longer than ∼ 10 bp unlikely on typical eukaryotic speciation timescales. Similarly, evolution converges to the stationary distribution of binding sequences very slowly, making the equilibrium assumption questionable. The availability of longer regulatory sequences in which multiple binding sites can evolve simultaneously, the presence of “pre-sites” or partially decayed old sites in the initial sequence, and biophysical cooperativity between transcription factors, can all facilitate gain of TFBS and reconcile theoretical calculations with timescales inferred from comparative genomics.
AU - Tugrul, Murat
AU - Paixao, Tiago
AU - Barton, Nicholas H
AU - Tkacik, Gasper
ID - 1666
IS - 11
JF - PLoS Genetics
TI - Dynamics of transcription factor binding site evolution
VL - 11
ER -
TY - GEN
AB - We study conditions under which a finite simplicial complex $K$ can be mapped to $\mathbb R^d$ without higher-multiplicity intersections. An almost $r$-embedding is a map $f: K\to \mathbb R^d$ such that the images of any $r$
pairwise disjoint simplices of $K$ do not have a common point. We show that if $r$ is not a prime power and $d\geq 2r+1$, then there is a counterexample to the topological Tverberg conjecture, i.e., there is an almost $r$-embedding of
the $(d+1)(r-1)$-simplex in $\mathbb R^d$. This improves on previous constructions of counterexamples (for $d\geq 3r$) based on a series of papers by M. \"Ozaydin, M. Gromov, P. Blagojevi\'c, F. Frick, G. Ziegler, and the second and fourth present authors. The counterexamples are obtained by proving the following algebraic criterion in codimension 2: If $r\ge3$ and if $K$ is a finite $2(r-1)$-complex then there exists an almost $r$-embedding $K\to \mathbb R^{2r}$ if and only if there exists a general position PL map $f:K\to \mathbb R^{2r}$ such that the algebraic intersection number of the $f$-images of any $r$ pairwise disjoint simplices of $K$ is zero. This result can be restated in terms of cohomological obstructions or equivariant maps, and extends an analogous codimension 3 criterion by the second and fourth authors. As another application we classify ornaments $f:S^3 \sqcup S^3\sqcup S^3\to \mathbb R^5$ up to ornament
concordance. It follows from work of M. Freedman, V. Krushkal and P. Teichner that the analogous criterion for $r=2$ is false. We prove a lemma on singular higher-dimensional Borromean rings, yielding an elementary proof of the counterexample.
AU - Avvakumov, Sergey
AU - Mabillard, Isaac
AU - Skopenkov, A.
AU - Wagner, Uli
ID - 8183
T2 - arXiv
TI - Eliminating higher-multiplicity intersections, III. Codimension 2
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 - We consider the core algorithmic problems related to verification of systems with respect to three classical quantitative properties, namely, the mean-payoff property, the ratio property, and the minimum initial credit for energy property. The algorithmic problem given a graph and a quantitative property asks to compute the optimal value (the infimum value over all traces) from every node of the graph. We consider graphs with constant treewidth, and it is well-known that the control-flow graphs of most programs have constant treewidth. Let n denote the number of nodes of a graph, m the number of edges (for constant treewidth graphs m=O(n)) and W the largest absolute value of the weights. Our main theoretical results are as follows. First, for constant treewidth graphs we present an algorithm that approximates the mean-payoff value within a multiplicative factor of ϵ in time O(n⋅log(n/ϵ)) and linear space, as compared to the classical algorithms that require quadratic time. Second, for the ratio property we present an algorithm that for constant treewidth graphs works in time O(n⋅log(|a⋅b|))=O(n⋅log(n⋅W)), when the output is ab, as compared to the previously best known algorithm with running time O(n2⋅log(n⋅W)). Third, for the minimum initial credit problem we show that (i) for general graphs the problem can be solved in O(n2⋅m) time and the associated decision problem can be solved in O(n⋅m) time, improving the previous known O(n3⋅m⋅log(n⋅W)) and O(n2⋅m) bounds, respectively; and (ii) for constant treewidth graphs we present an algorithm that requires O(n⋅logn) time, improving the previous known O(n4⋅log(n⋅W)) bound. We have implemented some of our algorithms and show that they present a significant speedup on standard benchmarks.
AU - Chatterjee, Krishnendu
AU - Ibsen-Jensen, Rasmus
AU - Pavlogiannis, Andreas
ID - 1607
TI - Faster algorithms for quantitative verification in constant treewidth graphs
VL - 9206
ER -
TY - JOUR
AB - The emergence of drug resistant pathogens is a serious public health problem. It is a long-standing goal to predict rates of resistance evolution and design optimal treatment strategies accordingly. To this end, it is crucial to reveal the underlying causes of drug-specific differences in the evolutionary dynamics leading to resistance. However, it remains largely unknown why the rates of resistance evolution via spontaneous mutations and the diversity of mutational paths vary substantially between drugs. Here we comprehensively quantify the distribution of fitness effects (DFE) of mutations, a key determinant of evolutionary dynamics, in the presence of eight antibiotics representing the main modes of action. Using precise high-throughput fitness measurements for genome-wide Escherichia coli gene deletion strains, we find that the width of the DFE varies dramatically between antibiotics and, contrary to conventional wisdom, for some drugs the DFE width is lower than in the absence of stress. We show that this previously underappreciated divergence in DFE width among antibiotics is largely caused by their distinct drug-specific dose-response characteristics. Unlike the DFE, the magnitude of the changes in tolerated drug concentration resulting from genome-wide mutations is similar for most drugs but exceptionally small for the antibiotic nitrofurantoin, i.e., mutations generally have considerably smaller resistance effects for nitrofurantoin than for other drugs. A population genetics model predicts that resistance evolution for drugs with this property is severely limited and confined to reproducible mutational paths. We tested this prediction in laboratory evolution experiments using the “morbidostat”, a device for evolving bacteria in well-controlled drug environments. Nitrofurantoin resistance indeed evolved extremely slowly via reproducible mutations—an almost paradoxical behavior since this drug causes DNA damage and increases the mutation rate. Overall, we identified novel quantitative characteristics of the evolutionary landscape that provide the conceptual foundation for predicting the dynamics of drug resistance evolution.
AU - Chevereau, Guillaume
AU - Dravecka, Marta
AU - Batur, Tugce
AU - Guvenek, Aysegul
AU - Ayhan, Dilay
AU - Toprak, Erdal
AU - Bollenbach, Mark Tobias
ID - 1619
IS - 11
JF - PLoS Biology
TI - Quantifying the determinants of evolutionary dynamics leading to drug resistance
VL - 13
ER -
TY - JOUR
AB - To reveal the full potential of human pluripotent stem cells, new methods for rapid, site-specific genomic engineering are needed. Here, we describe a system for precise genetic modification of human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). We identified a novel human locus, H11, located in a safe, intergenic, transcriptionally active region of chromosome 22, as the recipient site, to provide robust, ubiquitous expression of inserted genes. Recipient cell lines were established by site-specific placement of a ‘landing pad’ cassette carrying attP sites for phiC31 and Bxb1 integrases at the H11 locus by spontaneous or TALEN-assisted homologous recombination. Dual integrase cassette exchange (DICE) mediated by phiC31 and Bxb1 integrases was used to insert genes of interest flanked by phiC31 and Bxb1 attB sites at the H11 locus, replacing the landing pad. This system provided complete control over content, direction and copy number of inserted genes, with a specificity of 100%. A series of genes, including mCherry and various combinations of the neural transcription factors LMX1a, FOXA2 and OTX2, were inserted in recipient cell lines derived from H9 ESC, as well as iPSC lines derived from a Parkinson’s disease patient and a normal sibling control. The DICE system offers rapid, efficient and precise gene insertion in ESC and iPSC and is particularly well suited for repeated modifications of the same locus.
AU - Zhu, Fangfang
AU - Gamboa, Matthew
AU - Farruggio, Alfonso
AU - Hippenmeyer, Simon
AU - Tasic, Bosiljka
AU - Schüle, Birgitt
AU - Chen Tsai, Yanru
AU - Calos, Michele
ID - 2261
IS - 5
JF - Nucleic Acids Research
TI - DICE, an efficient system for iterative genomic editing in human pluripotent stem cells
VL - 42
ER -
TY - CHAP
AB - Coordinated migration of newly-born neurons to their target territories is essential for correct neuronal circuit assembly in the developing brain. Although a cohort of signaling pathways has been implicated in the regulation of cortical projection neuron migration, the precise molecular mechanisms and how a balanced interplay of cell-autonomous and non-autonomous functions of candidate signaling molecules controls the discrete steps in the migration process, are just being revealed. In this chapter, I will focally review recent advances that improved our understanding of the cell-autonomous and possible cell-nonautonomous functions of the evolutionarily conserved LIS1/NDEL1-complex in regulating the sequential steps of cortical projection neuron migration. I will then elaborate on the emerging concept that the Reelin signaling pathway, acts exactly at precise stages in the course of cortical projection neuron migration. Lastly, I will discuss how finely tuned transcriptional programs and downstream effectors govern particular aspects in driving radial migration at discrete stages and how they regulate the precise positioning of cortical projection neurons in the developing cerebral cortex.
AU - Hippenmeyer, Simon
ED - Nguyen, Laurent
ID - 2265
T2 - Cellular and Molecular Control of Neuronal Migration
TI - Molecular pathways controlling the sequential steps of cortical projection neuron migration
VL - 800
ER -
TY - CONF
AB - Energies with high-order non-submodular interactions have been shown to be very useful in vision due to their high modeling power. Optimization of such energies, however, is generally NP-hard. A naive approach that works for small problem instances is exhaustive search, that is, enumeration of all possible labelings of the underlying graph. We propose a general minimization approach for large graphs based on enumeration of labelings of certain small patches.
This partial enumeration technique reduces complex high-order energy formulations to pairwise Constraint Satisfaction Problems with unary costs (uCSP), which can be efficiently solved using standard methods like TRW-S. Our approach outperforms a number of existing state-of-the-art algorithms on well known difficult problems (e.g. curvature regularization, stereo, deconvolution); it gives near global minimum and better speed.
Our main application of interest is curvature regularization. In the context of segmentation, our partial enumeration technique allows to evaluate curvature directly on small patches using a novel integral geometry approach.
AU - Olsson, Carl
AU - Ulen, Johannes
AU - Boykov, Yuri
AU - Kolmogorov, Vladimir
ID - 2275
TI - Partial enumeration and curvature regularization
ER -
TY - JOUR
AB - GABAergic inhibitory interneurons control fundamental aspects of neuronal network function. Their functional roles are assumed to be defined by the identity of their input synapses, the architecture of their dendritic tree, the passive and active membrane properties and finally the nature of their postsynaptic targets. Indeed, interneurons display a high degree of morphological and physiological heterogeneity. However, whether their morphological and physiological characteristics are correlated and whether interneuron diversity can be described by a continuum of GABAergic cell types or by distinct classes has remained unclear. Here we perform a detailed morphological and physiological characterization of GABAergic cells in the dentate gyrus, the input region of the hippocampus. To achieve an unbiased and efficient sampling and classification we used knock-in mice expressing the enhanced green fluorescent protein (eGFP) in glutamate decarboxylase 67 (GAD67)-positive neurons and performed cluster analysis. We identified five interneuron classes, each of them characterized by a distinct set of anatomical and physiological parameters. Cross-correlation analysis further revealed a direct relation between morphological and physiological properties indicating that dentate gyrus interneurons fall into functionally distinct classes which may differentially control neuronal network activity.
AU - Hosp, Jonas
AU - Strüber, Michael
AU - Yanagawa, Yuchio
AU - Obata, Kunihiko
AU - Vida, Imre
AU - Jonas, Peter M
AU - Bartos, Marlene
ID - 2285
IS - 2
JF - Hippocampus
TI - Morpho-physiological criteria divide dentate gyrus interneurons into classes
VL - 23
ER -
TY - JOUR
AB - We prove the universality of the β-ensembles with convex analytic potentials and for any β >
0, i.e. we show that the spacing distributions of log-gases at any inverse temperature β coincide with those of the Gaussian β-ensembles.
AU - Erdös, László
AU - Bourgade, Paul
AU - Yau, Horng
ID - 2699
IS - 6
JF - Duke Mathematical Journal
TI - Universality of general β-ensembles
VL - 163
ER -
TY - JOUR
AB - Multi-dimensional mean-payoff and energy games provide the mathematical foundation for the quantitative study of reactive systems, and play a central role in the emerging quantitative theory of verification and synthesis. In this work, we study the strategy synthesis problem for games with such multi-dimensional objectives along with a parity condition, a canonical way to express ω ω -regular conditions. While in general, the winning strategies in such games may require infinite memory, for synthesis the most relevant problem is the construction of a finite-memory winning strategy (if one exists). Our main contributions are as follows. First, we show a tight exponential bound (matching upper and lower bounds) on the memory required for finite-memory winning strategies in both multi-dimensional mean-payoff and energy games along with parity objectives. This significantly improves the triple exponential upper bound for multi energy games (without parity) that could be derived from results in literature for games on vector addition systems with states. Second, we present an optimal symbolic and incremental algorithm to compute a finite-memory winning strategy (if one exists) in such games. Finally, we give a complete characterization of when finite memory of strategies can be traded off for randomness. In particular, we show that for one-dimension mean-payoff parity games, randomized memoryless strategies are as powerful as their pure finite-memory counterparts.
AU - Chatterjee, Krishnendu
AU - Randour, Mickael
AU - Raskin, Jean
ID - 2716
IS - 3-4
JF - Acta Informatica
TI - Strategy synthesis for multi-dimensional quantitative objectives
VL - 51
ER -
TY - JOUR
AB - A robust combiner for hash functions takes two candidate implementations and constructs a hash function which is secure as long as at least one of the candidates is secure. So far, hash function combiners only aim at preserving a single property such as collision-resistance or pseudorandomness. However, when hash functions are used in protocols like TLS they are often required to provide several properties simultaneously. We therefore put forward the notion of robust multi-property combiners and elaborate on different definitions for such combiners. We then propose a combiner that provably preserves (target) collision-resistance, pseudorandomness, and being a secure message authentication code. This combiner satisfies the strongest notion we propose, which requires that the combined function satisfies every security property which is satisfied by at least one of the underlying hash function. If the underlying hash functions have output length n, the combiner has output length 2 n. This basically matches a known lower bound for black-box combiners for collision-resistance only, thus the other properties can be achieved without penalizing the length of the hash values. We then propose a combiner which also preserves the property of being indifferentiable from a random oracle, slightly increasing the output length to 2 n+ω(log n). Moreover, we show how to augment our constructions in order to make them also robust for the one-wayness property, but in this case require an a priory upper bound on the input length.
AU - Fischlin, Marc
AU - Lehmann, Anja
AU - Pietrzak, Krzysztof Z
ID - 2852
IS - 3
JF - Journal of Cryptology
TI - Robust multi-property combiners for hash functions
VL - 27
ER -
TY - CONF
AB - Persistent homology is a recent grandchild of homology that has found use in
science and engineering as well as in mathematics. This paper surveys the method as well
as the applications, neglecting completeness in favor of highlighting ideas and directions.
AU - Edelsbrunner, Herbert
AU - Morozovy, Dmitriy
ID - 2905
TI - Persistent homology: Theory and practice
ER -
TY - CONF
AB - Many questions concerning models in quantum mechanics require a detailed analysis of the spectrum of the corresponding Hamiltonian, a linear operator on a suitable Hilbert space. Of particular relevance for an understanding of the low-temperature properties of a system is the structure of the excitation spectrum, which is the part of the spectrum close to the spectral bottom. We present recent progress on this question for bosonic many-body quantum systems with weak two-body interactions. Such system are currently of great interest, due to their experimental realization in ultra-cold atomic gases. We investigate the accuracy of the Bogoliubov approximations, which predicts that the low-energy spectrum is made up of sums of elementary excitations, with linear dispersion law at low momentum. The latter property is crucial for the superfluid behavior the system.
AU - Seiringer, Robert
ID - 8044
SN - 9788961058063
T2 - Proceeding of the International Congress of Mathematicans
TI - Structure of the excitation spectrum for many-body quantum systems
VL - 3
ER -
TY - JOUR
AB - The main model studied in this paper is a lattice of pendula with a nearest‐neighbor coupling. If the coupling is weak, then the system is near‐integrable and KAM tori fill most of the phase space. For all KAM trajectories the energy of each pendulum stays within a narrow band for all time. Still, we show that for an arbitrarily weak coupling of a certain localized type, the neighboring pendula can exchange energy. In fact, the energy can be transferred between the pendula in any prescribed way.
AU - Kaloshin, Vadim
AU - Levi, Mark
AU - Saprykina, Maria
ID - 8500
IS - 5
JF - Communications on Pure and Applied Mathematics
KW - Applied Mathematics
KW - General Mathematics
SN - 0010-3640
TI - Arnol′d diffusion in a pendulum lattice
VL - 67
ER -
TY - CONF
AB - In this paper we present INTERHORN, a solver for recursion-free Horn clauses. The main application domain of INTERHORN lies in solving interpolation problems arising in software verification. We show how a range of interpolation problems, including path, transition, nested, state/transition and well-founded interpolation can be handled directly by INTERHORN. By detailing these interpolation problems and their Horn clause representations, we hope to encourage the emergence of a common back-end interpolation interface useful for diverse verification tools.
AU - Gupta, Ashutosh
AU - Popeea, Corneliu
AU - Rybalchenko, Andrey
ID - 1702
T2 - Electronic Proceedings in Theoretical Computer Science, EPTCS
TI - Generalised interpolation by solving recursion free-horn clauses
VL - 169
ER -
TY - CONF
AB - It has been long argued that, because of inherent ambiguity and noise, the brain needs to represent uncertainty in the form of probability distributions. The neural encoding of such distributions remains however highly controversial. Here we present a novel circuit model for representing multidimensional real-valued distributions using a spike based spatio-temporal code. Our model combines the computational advantages of the currently competing models for probabilistic codes and exhibits realistic neural responses along a variety of classic measures. Furthermore, the model highlights the challenges associated with interpreting neural activity in relation to behavioral uncertainty and points to alternative population-level approaches for the experimental validation of distributed representations.
AU - Savin, Cristina
AU - Denève, Sophie
ID - 1708
IS - January
TI - Spatio-temporal representations of uncertainty in spiking neural networks
VL - 3
ER -
TY - JOUR
AB - The classical (boolean) notion of refinement for behavioral interfaces of system components is the alternating refinement preorder. In this paper, we define a distance for interfaces, called interface simulation distance. It makes the alternating refinement preorder quantitative by, intuitively, tolerating errors (while counting them) in the alternating simulation game. We show that the interface simulation distance satisfies the triangle inequality, that the distance between two interfaces does not increase under parallel composition with a third interface, that the distance between two interfaces can be bounded from above and below by distances between abstractions of the two interfaces, and how to synthesize an interface from incompatible requirements. We illustrate the framework, and the properties of the distances under composition of interfaces, with two case studies.
AU - Cerny, Pavol
AU - Chmelik, Martin
AU - Henzinger, Thomas A
AU - Radhakrishna, Arjun
ID - 1733
IS - 3
JF - Theoretical Computer Science
TI - Interface simulation distances
VL - 560
ER -
TY - CHAP
AB - The generation of asymmetry, at both cellular and tissue level, is one of the most essential capabilities of all eukaryotic organisms. It mediates basically all multicellular development ranging from embryogenesis and de novo organ formation till responses to various environmental stimuli. In plants, the awe-inspiring number of such processes is regulated by phytohormone auxin and its directional, cell-to-cell transport. The mediators of this transport, PIN auxin transporters, are asymmetrically localized at the plasma membrane, and this polar localization determines the directionality of intercellular auxin flow. Thus, auxin transport contributes crucially to the generation of local auxin gradients or maxima, which instruct given cell to change its developmental program. Here, we introduce and discuss the molecular components and cellular mechanisms regulating the generation and maintenance of cellular PIN polarity, as the general hallmarks of cell polarity in plants.
AU - Baster, Pawel
AU - Friml, Jiří
ED - Zažímalová, Eva
ED - Petrášek, Jan
ED - Benková, Eva
ID - 1806
T2 - Auxin and Its Role in Plant Development
TI - Auxin on the road navigated by cellular PIN polarity
ER -
TY - JOUR
AB - Watermarking techniques for vector graphics dislocate vertices in order to embed imperceptible, yet detectable, statistical features into the input data. The embedding process may result in a change of the topology of the input data, e.g., by introducing self-intersections, which is undesirable or even disastrous for many applications. In this paper we present a watermarking framework for two-dimensional vector graphics that employs conventional watermarking techniques but still provides the guarantee that the topology of the input data is preserved. The geometric part of this framework computes so-called maximum perturbation regions (MPR) of vertices. We propose two efficient algorithms to compute MPRs based on Voronoi diagrams and constrained triangulations. Furthermore, we present two algorithms to conditionally correct the watermarked data in order to increase the watermark embedding capacity and still guarantee topological correctness. While we focus on the watermarking of input formed by straight-line segments, one of our approaches can also be extended to circular arcs. We conclude the paper by demonstrating and analyzing the applicability of our framework in conjunction with two well-known watermarking techniques.
AU - Huber, Stefan
AU - Held, Martin
AU - Meerwald, Peter
AU - Kwitt, Roland
ID - 1816
IS - 1
JF - International Journal of Computational Geometry and Applications
TI - Topology-preserving watermarking of vector graphics
VL - 24
ER -
TY - JOUR
AB - We review recent progress towards a rigorous understanding of the Bogoliubov approximation for bosonic quantum many-body systems. We focus, in particular, on the excitation spectrum of a Bose gas in the mean-field (Hartree) limit. A list of open problems will be discussed at the end.
AU - Seiringer, Robert
ID - 1821
IS - 7
JF - Journal of Mathematical Physics
TI - Bose gases, Bose-Einstein condensation, and the Bogoliubov approximation
VL - 55
ER -
TY - JOUR
AU - Jakšić, Vojkan
AU - Pillet, Claude
AU - Seiringer, Robert
ID - 1822
IS - 7
JF - Journal of Mathematical Physics
TI - Introduction
VL - 55
ER -
TY - CHAP
AB - Hitting and batting tasks, such as tennis forehands, ping-pong strokes, or baseball batting, depend on predictions where the ball can be intercepted and how it can properly be returned to the opponent. These predictions get more accurate over time, hence the behaviors need to be continuously modified. As a result, movement templates with a learned global shape need to be adapted during the execution so that the racket reaches a target position and velocity that will return the ball over to the other side of the net or court. It requires altering learned movements to hit a varying target with the necessary velocity at a specific instant in time. Such a task cannot be incorporated straightforwardly in most movement representations suitable for learning. For example, the standard formulation of the dynamical system based motor primitives (introduced by Ijspeert et al (2002b)) does not satisfy this property despite their flexibility which has allowed learning tasks ranging from locomotion to kendama. In order to fulfill this requirement, we reformulate the Ijspeert framework to incorporate the possibility of specifying a desired hitting point and a desired hitting velocity while maintaining all advantages of the original formulation.We show that the proposed movement template formulation works well in two scenarios, i.e., for hitting a ball on a string with a table tennis racket at a specified velocity and for returning balls launched by a ball gun successfully over the net using forehand movements.
AU - Muelling, Katharina
AU - Kroemer, Oliver
AU - Lampert, Christoph
AU - Schölkopf, Bernhard
ED - Kober, Jens
ED - Peters, Jan
ID - 1829
T2 - Learning Motor Skills
TI - Movement templates for learning of hitting and batting
VL - 97
ER -
TY - JOUR
AB - We prove polynomial upper bounds of geometric Ramsey numbers of pathwidth-2 outerplanar triangulations in both convex and general cases. We also prove that the geometric Ramsey numbers of the ladder graph on 2n vertices are bounded by O(n3) and O(n10), in the convex and general case, respectively. We then apply similar methods to prove an (Formula presented.) upper bound on the Ramsey number of a path with n ordered vertices.
AU - Cibulka, Josef
AU - Gao, Pu
AU - Krcál, Marek
AU - Valla, Tomáš
AU - Valtr, Pavel
ID - 1842
IS - 1
JF - Discrete & Computational Geometry
TI - On the geometric ramsey number of outerplanar graphs
VL - 53
ER -
TY - JOUR
AB - Local protein interactions ("molecular context" effects) dictate amino acid replacements and can be described in terms of site-specific, energetic preferences for any different amino acid. It has been recently debated whether these preferences remain approximately constant during evolution or whether, due to coevolution of sites, they change strongly. Such research highlights an unresolved and fundamental issue with far-reaching implications for phylogenetic analysis and molecular evolution modeling. Here, we take advantage of the recent availability of phenotypically supported laboratory resurrections of Precambrian thioredoxins and β-lactamases to experimentally address the change of site-specific amino acid preferences over long geological timescales. Extensive mutational analyses support the notion that evolutionary adjustment to a new amino acid may occur, but to a large extent this is insufficient to erase the primitive preference for amino acid replacements. Generally, site-specific amino acid preferences appear to remain conserved throughout evolutionary history despite local sequence divergence. We show such preference conservation to be readily understandable in molecular terms and we provide crystallographic evidence for an intriguing structural-switch mechanism: Energetic preference for an ancestral amino acid in a modern protein can be linked to reorganization upon mutation to the ancestral local structure around the mutated site. Finally, we point out that site-specific preference conservation naturally leads to one plausible evolutionary explanation for the existence of intragenic global suppressor mutations.
AU - Risso, Valeria
AU - Manssour Triedo, Fadia
AU - Delgado Delgado, Asuncion
AU - Arco, Rocio
AU - Barroso Deljesús, Alicia
AU - Inglés Prieto, Álvaro
AU - Godoy Ruiz, Raquel
AU - Gavira, Josè
AU - Gaucher, Eric
AU - Ibarra Molero, Beatriz
AU - Sánchez Ruiz, Jose
ID - 1844
IS - 2
JF - Molecular Biology and Evolution
TI - Mutational studies on resurrected ancestral proteins reveal conservation of site-specific amino acid preferences throughout evolutionary history
VL - 32
ER -
TY - JOUR
AB - To control morphogenesis, molecular regulatory networks have to interfere with the mechanical properties of the individual cells of developing organs and tissues, but how this is achieved is not well known. We study this issue here in the shoot meristem of higher plants, a group of undifferentiated cells where complex changes in growth rates and directions lead to the continuous formation of new organs [1, 2]. Here, we show that the plant hormone auxin plays an important role in this process via a dual, local effect on the extracellular matrix, the cell wall, which determines cell shape. Our study reveals that auxin not only causes a limited reduction in wall stiffness but also directly interferes with wall anisotropy via the regulation of cortical microtubule dynamics. We further show that to induce growth isotropy and organ outgrowth, auxin somehow interferes with the cortical microtubule-ordering activity of a network of proteins, including AUXIN BINDING PROTEIN 1 and KATANIN 1. Numerical simulations further indicate that the induced isotropy is sufficient to amplify the effects of the relatively minor changes in wall stiffness to promote organogenesis and the establishment of new growth axes in a robust manner.
AU - Sassi, Massimiliano
AU - Ali, Olivier
AU - Boudon, Frédéric
AU - Cloarec, Gladys
AU - Abad, Ursula
AU - Cellier, Coralie
AU - Chen, Xu
AU - Gilles, Benjamin
AU - Milani, Pascale
AU - Friml, Jirí
AU - Vernoux, Teva
AU - Godin, Christophe
AU - Hamant, Olivier
AU - Traas, Jan
ID - 1852
IS - 19
JF - Current Biology
TI - An auxin-mediated shift toward growth isotropy promotes organ formation at the shoot meristem in Arabidopsis
VL - 24
ER -
TY - CONF
AB - Wireless sensor networks (WSNs) composed of low-power, low-cost sensor nodes are expected to form the backbone of future intelligent networks for a broad range of civil, industrial and military applications. These sensor nodes are often deployed through random spreading, and function in dynamic environments. Many applications of WSNs such as pollution tracking, forest fire detection, and military surveillance require knowledge of the location of constituent nodes. But the use of technologies such as GPS on all nodes is prohibitive due to power and cost constraints. So, the sensor nodes need to autonomously determine their locations. Most localization techniques use anchor nodes with known locations to determine the position of remaining nodes. Localization techniques have two conflicting requirements. On one hand, an ideal localization technique should be computationally simple and on the other hand, it must be resistant to attacks that compromise anchor nodes. In this paper, we propose a computationally light-weight game theoretic secure localization technique and demonstrate its effectiveness in comparison to existing techniques.
AU - Jha, Susmit
AU - Tripakis, Stavros
AU - Seshia, Sanjit
AU - Chatterjee, Krishnendu
ID - 1853
TI - Game theoretic secure localization in wireless sensor networks
ER -
TY - JOUR
AB - In this paper, we present a method for non-rigid, partial shape matching in vector graphics. Given a user-specified query region in a 2D shape, similar regions are found, even if they are non-linearly distorted. Furthermore, a non-linear mapping is established between the query regions and these matches, which allows the automatic transfer of editing operations such as texturing. This is achieved by a two-step approach. First, pointwise correspondences between the query region and the whole shape are established. The transformation parameters of these correspondences are registered in an appropriate transformation space. For transformations between similar regions, these parameters form surfaces in transformation space, which are extracted in the second step of our method. The extracted regions may be related to the query region by a non-rigid transform, enabling non-rigid shape matching. In this paper, we present a method for non-rigid, partial shape matching in vector graphics. Given a user-specified query region in a 2D shape, similar regions are found, even if they are non-linearly distorted. Furthermore, a non-linear mapping is established between the query regions and these matches, which allows the automatic transfer of editing operations such as texturing. This is achieved by a two-step approach. First, pointwise correspondences between the query region and the whole shape are established. The transformation parameters of these correspondences are registered in an appropriate transformation space. For transformations between similar regions, these parameters form surfaces in transformation space, which are extracted in the second step of our method. The extracted regions may be related to the query region by a non-rigid transform, enabling non-rigid shape matching.
AU - Guerrero, Paul
AU - Auzinger, Thomas
AU - Wimmer, Michael
AU - Jeschke, Stefan
ID - 1854
IS - 1
JF - Computer Graphics Forum
TI - Partial shape matching using transformation parameter similarity
VL - 34
ER -
TY - JOUR
AB - The prominent and evolutionarily ancient role of the plant hormone auxin is the regulation of cell expansion. Cell expansion requires ordered arrangement of the cytoskeleton but molecular mechanisms underlying its regulation by signalling molecules including auxin are unknown. Here we show in the model plant Arabidopsis thaliana that in elongating cells exogenous application of auxin or redistribution of endogenous auxin induces very rapid microtubule re-orientation from transverse to longitudinal, coherent with the inhibition of cell expansion. This fast auxin effect requires auxin binding protein 1 (ABP1) and involves a contribution of downstream signalling components such as ROP6 GTPase, ROP-interactive protein RIC1 and the microtubule-severing protein katanin. These components are required for rapid auxin-and ABP1-mediated re-orientation of microtubules to regulate cell elongation in roots and dark-grown hypocotyls as well as asymmetric growth during gravitropic responses.
AU - Chen, Xu
AU - Grandont, Laurie
AU - Li, Hongjiang
AU - Hauschild, Robert
AU - Paque, Sébastien
AU - Abuzeineh, Anas
AU - Rakusová, Hana
AU - Benková, Eva
AU - Perrot Rechenmann, Catherine
AU - Friml, Jirí
ID - 1862
IS - 729
JF - Nature
TI - Inhibition of cell expansion by rapid ABP1-mediated auxin effect on microtubules
VL - 516
ER -
TY - CONF
AB - Boolean controllers for systems with complex datapaths are often very difficult to implement correctly, in particular when concurrency is involved. Yet, in many instances it is easy to formally specify correctness. For example, the specification for the controller of a pipelined processor only has to state that the pipelined processor gives the same results as a non-pipelined reference design. This makes such controllers a good target for automated synthesis. However, an efficient abstraction for the complex datapath elements is needed, as a bit-precise description is often infeasible. We present Suraq, the first controller synthesis tool which uses uninterpreted functions for the abstraction. Quantified firstorder formulas (with specific quantifier structure) serve as the specification language from which Suraq synthesizes Boolean controllers. Suraq transforms the specification into an unsatisfiable SMT formula, and uses Craig interpolation to compute its results. Using Suraq, we were able to synthesize a controller (consisting of two Boolean signals) for a five-stage pipelined DLX processor in roughly one hour and 15 minutes.
AU - Hofferek, Georg
AU - Gupta, Ashutosh
ED - Yahav, Eran
ID - 1869
T2 - HVC 2014
TI - Suraq - a controller synthesis tool using uninterpreted functions
VL - 8855
ER -
TY - CONF
AB - We investigate the problem of checking if a finite-state transducer is robust to uncertainty in its input. Our notion of robustness is based on the analytic notion of Lipschitz continuity - a transducer is K-(Lipschitz) robust if the perturbation in its output is at most K times the perturbation in its input. We quantify input and output perturbation using similarity functions. We show that K-robustness is undecidable even for deterministic transducers. We identify a class of functional transducers, which admits a polynomial time automata-theoretic decision procedure for K-robustness. This class includes Mealy machines and functional letter-to-letter transducers. We also study K-robustness of nondeterministic transducers. Since a nondeterministic transducer generates a set of output words for each input word, we quantify output perturbation using setsimilarity functions. We show that K-robustness of nondeterministic transducers is undecidable, even for letter-to-letter transducers. We identify a class of set-similarity functions which admit decidable K-robustness of letter-to-letter transducers.
AU - Henzinger, Thomas A
AU - Otop, Jan
AU - Samanta, Roopsha
ID - 1870
T2 - Leibniz International Proceedings in Informatics, LIPIcs
TI - Lipschitz robustness of finite-state transducers
VL - 29
ER -
TY - CONF
AB - Extensionality axioms are common when reasoning about data collections, such as arrays and functions in program analysis, or sets in mathematics. An extensionality axiom asserts that two collections are equal if they consist of the same elements at the same indices. Using extensionality is often required to show that two collections are equal. A typical example is the set theory theorem (∀x)(∀y)x∪y = y ∪x. Interestingly, while humans have no problem with proving such set identities using extensionality, they are very hard for superposition theorem provers because of the calculi they use. In this paper we show how addition of a new inference rule, called extensionality resolution, allows first-order theorem provers to easily solve problems no modern first-order theorem prover can solve. We illustrate this by running the VAMPIRE theorem prover with extensionality resolution on a number of set theory and array problems. Extensionality resolution helps VAMPIRE to solve problems from the TPTP library of first-order problems that were never solved before by any prover.
AU - Gupta, Ashutosh
AU - Kovács, Laura
AU - Kragl, Bernhard
AU - Voronkov, Andrei
ED - Cassez, Franck
ED - Raskin, Jean-François
ID - 1872
T2 - ATVA 2014
TI - Extensional crisis and proving identity
VL - 8837
ER -
TY - CONF
AB - We present a formal framework for repairing infinite-state, imperative, sequential programs, with (possibly recursive) procedures and multiple assertions; the framework can generate repaired programs by modifying the original erroneous program in multiple program locations, and can ensure the readability of the repaired program using user-defined expression templates; the framework also generates a set of inductive assertions that serve as a proof of correctness of the repaired program. As a step toward integrating programmer intent and intuition in automated program repair, we present a cost-aware formulation - given a cost function associated with permissible statement modifications, the goal is to ensure that the total program modification cost does not exceed a given repair budget. As part of our predicate abstractionbased solution framework, we present a sound and complete algorithm for repair of Boolean programs. We have developed a prototype tool based on SMT solving and used it successfully to repair diverse errors in benchmark C programs.
AU - Samanta, Roopsha
AU - Olivo, Oswaldo
AU - Allen, Emerson
ED - Müller-Olm, Markus
ED - Seidl, Helmut
ID - 1875
TI - Cost-aware automatic program repair
VL - 8723
ER -
TY - JOUR
AB - We study densities of functionals over uniformly bounded triangulations of a Delaunay set of vertices, and prove that the minimum is attained for the Delaunay triangulation if this is the case for finite sets.
AU - Dolbilin, Nikolai
AU - Edelsbrunner, Herbert
AU - Glazyrin, Alexey
AU - Musin, Oleg
ID - 1876
IS - 3
JF - Moscow Mathematical Journal
TI - Functionals on triangulations of delaunay sets
VL - 14
ER -
TY - JOUR
AB - During inflammation, lymph nodes swell with an influx of immune cells. New findings identify a signalling pathway that induces relaxation in the contractile cells that give structure to these organs.
AU - Sixt, Michael K
AU - Vaahtomeri, Kari
ID - 1877
IS - 7523
JF - Nature
TI - Physiology: Relax and come in
VL - 514
ER -
TY - JOUR
AB - Unbiased high-throughput massively parallel sequencing methods have transformed the process of discovery of novel putative driver gene mutations in cancer. In chronic lymphocytic leukemia (CLL), these methods have yielded several unexpected findings, including the driver genes SF3B1, NOTCH1 and POT1. Recent analysis, utilizing down-sampling of existing datasets, has shown that the discovery process of putative drivers is far from complete across cancer. In CLL, while driver gene mutations affecting >10% of patients were efficiently discovered with previously published CLL cohorts of up to 160 samples subjected to whole exome sequencing (WES), this sample size has only 0.78 power to detect drivers affecting 5% of patients, and only 0.12 power for drivers affecting 2% of patients. These calculations emphasize the need to apply unbiased WES to larger patient cohorts.
AU - Landau, Dan
AU - Stewart, Chip
AU - Reiter, Johannes
AU - Lawrence, Michael
AU - Sougnez, Carrie
AU - Brown, Jennifer
AU - Lopez Guillermo, Armando
AU - Gabriel, Stacey
AU - Lander, Eric
AU - Neuberg, Donna
AU - López Otín, Carlos
AU - Campo, Elias
AU - Getz, Gad
AU - Wu, Catherine
ID - 1884
IS - 21
JF - Blood
TI - Novel putative driver gene mutations in chronic lymphocytic leukemia (CLL): results from a combined analysis of whole exome sequencing of 262 primary CLL aamples
VL - 124
ER -
TY - JOUR
AB - Information processing in the sensory periphery is shaped by natural stimulus statistics. In the periphery, a transmission bottleneck constrains performance; thus efficient coding implies that natural signal components with a predictably wider range should be compressed. In a different regime—when sampling limitations constrain performance—efficient coding implies that more resources should be allocated to informative features that are more variable. We propose that this regime is relevant for sensory cortex when it extracts complex features from limited numbers of sensory samples. To test this prediction, we use central visual processing as a model: we show that visual sensitivity for local multi-point spatial correlations, described by dozens of independently-measured parameters, can be quantitatively predicted from the structure of natural images. This suggests that efficient coding applies centrally, where it extends to higher-order sensory features and operates in a regime in which sensitivity increases with feature variability.
AU - Hermundstad, Ann
AU - Briguglio, John
AU - Conte, Mary
AU - Victor, Jonathan
AU - Balasubramanian, Vijay
AU - Tkacik, Gasper
ID - 1886
IS - November
JF - eLife
TI - Variance predicts salience in central sensory processing
ER -