TY - JOUR
AB - Given a finite set of points in Rn and a radius parameter, we study the Čech, Delaunay–Čech, Delaunay (or alpha), and Wrap complexes in the light of generalized discrete Morse theory. Establishing the Čech and Delaunay complexes as sublevel sets of generalized discrete Morse functions, we prove that the four complexes are simple-homotopy equivalent by a sequence of simplicial collapses, which are explicitly described by a single discrete gradient field.
AU - Bauer, Ulrich
AU - Edelsbrunner, Herbert
ID - 1072
IS - 5
JF - Transactions of the American Mathematical Society
TI - The Morse theory of Čech and delaunay complexes
VL - 369
ER -
TY - JOUR
AB - Let X and Y be finite simplicial sets (e.g. finite simplicial complexes), both equipped with a free simplicial action of a finite group G. Assuming that Y is d-connected and dimX≤2d, for some d≥1, we provide an algorithm that computes the set of all equivariant homotopy classes of equivariant continuous maps |X|→|Y|; the existence of such a map can be decided even for dimX≤2d+1. This yields the first algorithm for deciding topological embeddability of a k-dimensional finite simplicial complex into Rn under the condition k≤23n−1. More generally, we present an algorithm that, given a lifting-extension problem satisfying an appropriate stability assumption, computes the set of all homotopy classes of solutions. This result is new even in the non-equivariant situation.
AU - Čadek, Martin
AU - Krcál, Marek
AU - Vokřínek, Lukáš
ID - 1073
IS - 4
JF - Discrete & Computational Geometry
SN - 01795376
TI - Algorithmic solvability of the lifting extension problem
VL - 54
ER -
TY - JOUR
AB - Recently it has become feasible to detect long blocks of nearly identical sequence shared between pairs of genomes. These IBD blocks are direct traces of recent coalescence events and, as such, contain ample signal to infer recent demography. Here, we examine sharing of such blocks in two-dimensional populations with local migration. Using a diffusion approximation to trace genetic ancestry, we derive analytical formulae for patterns of isolation by distance of IBD blocks, which can also incorporate recent population density changes. We introduce an inference scheme that uses a composite likelihood approach to fit these formulae. We then extensively evaluate our theory and inference method on a range of scenarios using simulated data. We first validate the diffusion approximation by showing that the theoretical results closely match the simulated block sharing patterns. We then demonstrate that our inference scheme can accurately and robustly infer dispersal rate and effective density, as well as bounds on recent dynamics of population density. To demonstrate an application, we use our estimation scheme to explore the fit of a diffusion model to Eastern European samples in the POPRES data set. We show that ancestry diffusing with a rate of σ ≈ 50–100 km/√gen during the last centuries, combined with accelerating population growth, can explain the observed exponential decay of block sharing with increasing pairwise sample distance.
AU - Ringbauer, Harald
AU - Coop, Graham
AU - Barton, Nicholas H
ID - 1074
IS - 3
JF - Genetics
SN - 00166731
TI - Inferring recent demography from isolation by distance of long shared sequence blocks
VL - 205
ER -
TY - JOUR
AB - Signatures of the Coulomb corrections in the photoelectron momentum distribution during laser-induced ionization of atoms or ions in tunneling and multiphoton regimes are investigated analytically in the case of a one-dimensional problem. A high-order Coulomb-corrected strong-field approximation is applied, where the exact continuum state in the S matrix is approximated by the eikonal Coulomb-Volkov state including the second-order corrections to the eikonal. Although without high-order corrections our theory coincides with the known analytical R-matrix (ARM) theory, we propose a simplified procedure for the matrix element derivation. Rather than matching the eikonal Coulomb-Volkov wave function with the bound state as in the ARM theory to remove the Coulomb singularity, we calculate the matrix element via the saddle-point integration method by time as well as by coordinate, and in this way avoiding the Coulomb singularity. The momentum shift in the photoelectron momentum distribution with respect to the ARM theory due to high-order corrections is analyzed for tunneling and multiphoton regimes. The relation of the quantum corrections to the tunneling delay time is discussed.
AU - Klaiber, Michael
AU - Daněk, Jiří
AU - Yakaboylu, Enderalp
AU - Hatsagortsyan, Karen
AU - Keitel, Christoph
ID - 1076
IS - 2
JF - Physical Review A - Atomic, Molecular, and Optical Physics
SN - 24699926
TI - Strong-field ionization via a high-order Coulomb-corrected strong-field approximation
VL - 95
ER -
TY - JOUR
AB - Viral capsids are structurally constrained by interactions among the amino acids (AAs) of their constituent proteins. Therefore, epistasis is expected to evolve among physically interacting sites and to influence the rates of substitution. To study the evolution of epistasis, we focused on the major structural protein of the fX174 phage family by first reconstructing the ancestral protein sequences of 18 species using a Bayesian statistical framework. The inferred ancestral reconstruction differed at eight AAs, for a total of 256 possible ancestral haplotypes. For each ancestral haplotype and the extant species, we estimated, in silico, the distribution of free energies and epistasis of the capsid structure. We found that free energy has not significantly increased but epistasis has. We decomposed epistasis up to fifth order and found that higher-order epistasis sometimes compensates pairwise interactions making the free energy seem additive. The dN/dS ratio is low, suggesting strong purifying selection, and that structure is under stabilizing selection. We synthesized phages carrying ancestral haplotypes of the coat protein gene and measured their fitness experimentally. Our findings indicate that stabilizing mutations can have higher fitness, and that fitness optima do not necessarily coincide with energy minima.
AU - Fernandes Redondo, Rodrigo A
AU - Vladar, Harold
AU - Włodarski, Tomasz
AU - Bollback, Jonathan P
ID - 1077
IS - 126
JF - Journal of the Royal Society Interface
SN - 17425689
TI - Evolutionary interplay between structure, energy and epistasis in the coat protein of the fX174 phage family
VL - 14
ER -
TY - JOUR
AB - One of the key questions in understanding plant development is how single cells behave in a larger context of the tissue. Therefore, it requires the observation of the whole organ with a high spatial- as well as temporal resolution over prolonged periods of time, which may cause photo-toxic effects. This protocol shows a plant sample preparation method for light-sheet microscopy, which is characterized by mounting the plant vertically on the surface of a gel. The plant is mounted in such a way that the roots are submerged in a liquid medium while the leaves remain in the air. In order to ensure photosynthetic activity of the plant, a custom-made lighting system illuminates the leaves. To keep the roots in darkness the water surface is covered with sheets of black plastic foil. This method allows long-term imaging of plant organ development in standardized conditions.
AU - Von Wangenheim, Daniel
AU - Hauschild, Robert
AU - Friml, Jirí
ID - 1078
IS - 119
JF - Journal of visualized experiments JoVE
TI - Light sheet fluorescence microscopy of plant roots growing on the surface of a gel
VL - 2017
ER -
TY - JOUR
AB - We study the ionization problem in the Thomas-Fermi-Dirac-von Weizsäcker theory for atoms and molecules. We prove the nonexistence of minimizers for the energy functional when the number of electrons is large and the total nuclear charge is small. This nonexistence result also applies to external potentials decaying faster than the Coulomb potential. In the case of arbitrary nuclear charges, we obtain the nonexistence of stable minimizers and radial minimizers.
AU - Nam, Phan
AU - Van Den Bosch, Hanne
ID - 1079
IS - 2
JF - Mathematical Physics, Analysis and Geometry
SN - 13850172
TI - Nonexistence in Thomas Fermi-Dirac-von Weizsäcker theory with small nuclear charges
VL - 20
ER -
TY - JOUR
AB - Reconstructing the evolutionary history of metastases is critical for understanding their basic biological principles and has profound clinical implications. Genome-wide sequencing data has enabled modern phylogenomic methods to accurately dissect subclones and their phylogenies from noisy and impure bulk tumour samples at unprecedented depth. However, existing methods are not designed to infer metastatic seeding patterns. Here we develop a tool, called Treeomics, to reconstruct the phylogeny of metastases and map subclones to their anatomic locations. Treeomics infers comprehensive seeding patterns for pancreatic, ovarian, and prostate cancers. Moreover, Treeomics correctly disambiguates true seeding patterns from sequencing artifacts; 7% of variants were misclassified by conventional statistical methods. These artifacts can skew phylogenies by creating illusory tumour heterogeneity among distinct samples. In silico benchmarking on simulated tumour phylogenies across a wide range of sample purities (15–95%) and sequencing depths (25-800 × ) demonstrates the accuracy of Treeomics compared with existing methods.
AU - Reiter, Johannes
AU - Makohon Moore, Alvin
AU - Gerold, Jeffrey
AU - Božić, Ivana
AU - Chatterjee, Krishnendu
AU - Iacobuzio Donahue, Christine
AU - Vogelstein, Bert
AU - Nowak, Martin
ID - 1080
JF - Nature Communications
SN - 20411723
TI - Reconstructing metastatic seeding patterns of human cancers
VL - 8
ER -
TY - JOUR
AB - BceRS and PsdRS are paralogous two-component systems in Bacillus subtilis controlling the response to antimicrobial peptides. In the presence of extracellular bacitracin and nisin, respectively, the two response regulators (RRs) bind their target promoters, PbceA or PpsdA, resulting in a strong up-regulation of target gene expression and ultimately antibiotic resistance. Despite high sequence similarity between the RRs BceR and PsdR and their known binding sites, no cross-regulation has been observed between them. We therefore investigated the specificity determinants of PbceA and PpsdA that ensure the insulation of these two paralogous pathways at the RR–promoter interface. In vivo and in vitro analyses demonstrate that the regulatory regions within these two promoters contain three important elements: in addition to the known (main) binding site, we identified a linker region and a secondary binding site that are crucial for functionality. Initial binding to the high-affinity, low-specificity main binding site is a prerequisite for the subsequent highly specific binding of a second RR dimer to the low-affinity secondary binding site. In addition to this hierarchical cooperative binding, discrimination requires a competition of the two RRs for their respective binding site mediated by only slight differences in binding affinities.
AU - Fang, Chong
AU - Nagy-Staron, Anna A
AU - Grafe, Martin
AU - Heermann, Ralf
AU - Jung, Kirsten
AU - Gebhard, Susanne
AU - Mascher, Thorsten
ID - 1084
IS - 1
JF - Molecular Microbiology
SN - 0950382X
TI - Insulation and wiring specificity of BceR like response regulators and their target promoters in Bacillus subtilis
VL - 104
ER -
TY - JOUR
AB - Sex chromosomes evolve once recombination is halted between a homologous pair of chromosomes. The dominant model of sex chromosome evolution posits that recombination is suppressed between emerging X and Y chromosomes in order to resolve sexual conflict. Here we test this model using whole genome and transcriptome resequencing data in the guppy, a model for sexual selection with many Y-linked colour traits. We show that although the nascent Y chromosome encompasses nearly half of the linkage group, there has been no perceptible degradation of Y chromosome gene content or activity. Using replicate wild populations with differing levels of sexually antagonistic selection for colour, we also show that sexual selection leads to greater expansion of the non-recombining region and increased Y chromosome divergence. These results provide empirical support for longstanding models of sex chromosome catalysis, and suggest an important role for sexual selection and sexual conflict in genome evolution.
AU - Wright, Alison
AU - Darolti, Iulia
AU - Bloch, Natasha
AU - Oostra, Vicencio
AU - Sandkam, Benjamin
AU - Buechel, Séverine
AU - Kolm, Niclas
AU - Breden, Felix
AU - Vicoso, Beatriz
AU - Mank, Judith
ID - 1085
JF - Nature Communications
SN - 20411723
TI - Convergent recombination suppression suggests role of sexual selection in guppy sex chromosome formation
VL - 8
ER -
TY - JOUR
AB - Characterisation of G protein-coupled receptors (GPCR) relies on the availability of a toolbox of ligands that selectively modulate different functional states of the receptors. To uncover such molecules, we explored a unique strategy for ligand discovery that takes advantage of the evolutionary conservation of the 600-million-year-old oxytocin/vasopressin signalling system. We isolated the insect oxytocin/vasopressin orthologue inotocin from the black garden ant (Lasius niger), identified and cloned its cognate receptor and determined its pharmacological properties on the insect and human oxytocin/vasopressin receptors. Subsequently, we identified a functional dichotomy: inotocin activated the insect inotocin and the human vasopressin V1b receptors, but inhibited the human V1aR. Replacement of Arg8 of inotocin by D-Arg8 led to a potent, stable and competitive V1aR-antagonist ([D-Arg8]-inotocin) with a 3,000-fold binding selectivity for the human V1aR over the other three subtypes, OTR, V1bR and V2R. The Arg8/D-Arg8 ligand-pair was further investigated to gain novel insights into the oxytocin/vasopressin peptide-receptor interaction, which led to the identification of key residues of the receptors that are important for ligand functionality and selectivity. These observations could play an important role for development of oxytocin/vasopressin receptor modulators that would enable clear distinction of the physiological and pathological responses of the individual receptor subtypes.
AU - Di Giglio, Maria
AU - Muttenthaler, Markus
AU - Harpsøe, Kasper
AU - Liutkeviciute, Zita
AU - Keov, Peter
AU - Eder, Thomas
AU - Rattei, Thomas
AU - Arrowsmith, Sarah
AU - Wray, Susan
AU - Marek, Ales
AU - Elbert, Tomas
AU - Alewood, Paul
AU - Gloriam, David
AU - Gruber, Christian
ID - 1086
JF - Scientific Reports
TI - Development of a human vasopressin V1a-receptor antagonist from an evolutionary-related insect neuropeptide
VL - 7
ER -
TY - JOUR
AB - Using extensive direct numerical simulations, the dynamics of laminar-turbulent fronts in pipe flow is investigated for Reynolds numbers between and 5500. We here investigate the physical distinction between the fronts of weak and strong slugs both by analysing the turbulent kinetic energy budget and by comparing the downstream front motion to the advection speed of bulk turbulent structures. Our study shows that weak downstream fronts travel slower than turbulent structures in the bulk and correspond to decaying turbulence at the front. At the downstream front speed becomes faster than the advection speed, marking the onset of strong fronts. In contrast to weak fronts, turbulent eddies are generated at strong fronts by feeding on the downstream laminar flow. Our study also suggests that temporal fluctuations of production and dissipation at the downstream laminar-turbulent front drive the dynamical switches between the two types of front observed up to.
AU - Song, Baofang
AU - Barkley, Dwight
AU - Hof, Björn
AU - Avila, Marc
ID - 1087
JF - Journal of Fluid Mechanics
SN - 00221120
TI - Speed and structure of turbulent fronts in pipe flow
VL - 813
ER -
TY - JOUR
AB - We discuss properties of distributions that are multivariate totally positive of order two (MTP2) related to conditional independence. In particular, we show that any independence model generated by an MTP2 distribution is a compositional semigraphoid which is upward-stable and singleton-transitive. In addition, we prove that any MTP2 distribution satisfying an appropriate support condition is faithful to its concentration graph. Finally, we analyze factorization properties of MTP2 distributions and discuss ways of constructing MTP2 distributions; in particular we give conditions on the log-linear parameters of a discrete distribution which ensure MTP2 and characterize conditional Gaussian distributions which satisfy MTP2.
AU - Fallat, Shaun
AU - Lauritzen, Steffen
AU - Sadeghi, Kayvan
AU - Uhler, Caroline
AU - Wermuth, Nanny
AU - Zwiernik, Piotr
ID - 1089
IS - 3
JF - Annals of Statistics
SN - 00905364
TI - Total positivity in Markov structures
VL - 45
ER -
TY - JOUR
AB - In the early visual system, cells of the same type perform the same computation in different places of the visual field. How these cells code together a complex visual scene is unclear. A common assumption is that cells of a single-type extract a single-stimulus feature to form a feature map, but this has rarely been observed directly. Using large-scale recordings in the rat retina, we show that a homogeneous population of fast OFF ganglion cells simultaneously encodes two radically different features of a visual scene. Cells close to a moving object code quasilinearly for its position, while distant cells remain largely invariant to the object's position and, instead, respond nonlinearly to changes in the object's speed. We develop a quantitative model that accounts for this effect and identify a disinhibitory circuit that mediates it. Ganglion cells of a single type thus do not code for one, but two features simultaneously. This richer, flexible neural map might also be present in other sensory systems.
AU - Deny, Stephane
AU - Ferrari, Ulisse
AU - Mace, Emilie
AU - Yger, Pierre
AU - Caplette, Romain
AU - Picaud, Serge
AU - Tkacik, Gasper
AU - Marre, Olivier
ID - 1104
IS - 1
JF - Nature Communications
SN - 20411723
TI - Multiplexed computations in retinal ganglion cells of a single type
VL - 8
ER -
TY - CONF
AB - In this work we study the learnability of stochastic processes with respect to the conditional risk, i.e. the existence of a learning algorithm that improves its next-step performance with the amount of observed data. We introduce a notion of pairwise discrepancy between conditional distributions at different times steps and show how certain properties of these discrepancies can be used to construct a successful learning algorithm. Our main results are two theorems that establish criteria for learnability for many classes of stochastic processes, including all special cases studied previously in the literature.
AU - Zimin, Alexander
AU - Lampert, Christoph
ID - 1108
TI - Learning theory for conditional risk minimization
VL - 54
ER -
TY - JOUR
AB - Rotation of molecules embedded in He nanodroplets is explored by a combination of fs laser-induced alignment experiments and angulon quasiparticle theory. We demonstrate that at low fluence of the fs alignment pulse, the molecule and its solvation shell can be set into coherent collective rotation lasting long enough to form revivals. With increasing fluence, however, the revivals disappear -- instead, rotational dynamics as rapid as for an isolated molecule is observed during the first few picoseconds. Classical calculations trace this phenomenon to transient decoupling of the molecule from its He shell. Our results open novel opportunities for studying non-equilibrium solute-solvent dynamics and quantum thermalization.
AU - Shepperson, Benjamin
AU - Søndergaard, Anders
AU - Christiansen, Lars
AU - Kaczmarczyk, Jan
AU - Zillich, Robert
AU - Lemeshko, Mikhail
AU - Stapelfeldt, Henrik
ID - 1109
IS - 20
JF - Physical Review Letters
TI - Laser-induced rotation of iodine molecules in helium nanodroplets: Revivals and breaking-free
VL - 118
ER -
TY - JOUR
AB - The phytohormone auxin is a major determinant and regulatory component important for plant development. Auxin transport between cells is mediated by a complex system of transporters such as AUX1/LAX, PIN, and ABCB proteins, and their localization and activity is thought to be influenced by phosphatases and kinases. Flavonols have been shown to alter auxin transport activity and changes in flavonol accumulation in the Arabidopsis thaliana rol1-2 mutant cause defects in auxin transport and seedling development. A new mutation in ROOTS CURL IN NPA 1 (RCN1), encoding a regulatory subunit of the phosphatase PP2A, was found to suppress the growth defects of rol1-2 without changing the flavonol content. rol1-2 rcn1-3 double mutants show wild type-like auxin transport activity while levels of free auxin are not affected by rcn1-3. In the rol1-2 mutant, PIN2 shows a flavonol-induced basal-to-apical shift in polar localization which is reversed in the rol1-2 rcn1-3 to basal localization. In vivo analysis of PINOID action, a kinase known to influence PIN protein localization in a PP2A-antagonistic manner, revealed a negative impact of flavonols on PINOID activity. Together, these data suggest that flavonols affect auxin transport by modifying the antagonistic kinase/phosphatase equilibrium.
AU - Kuhn, Benjamin
AU - Nodzyński, Tomasz
AU - Errafi, Sanae
AU - Bucher, Rahel
AU - Gupta, Shibu
AU - Aryal, Bibek
AU - Dobrev, Petre
AU - Bigler, Laurent
AU - Geisler, Markus
AU - Zažímalová, Eva
AU - Friml, Jirí
AU - Ringli, Christoph
ID - 1110
JF - Scientific Reports
SN - 20452322
TI - Flavonol-induced changes in PIN2 polarity and auxin transport in the Arabidopsis thaliana rol1-2 mutant require phosphatase activity
VL - 7
ER -
TY - JOUR
AB - Adaptation depends critically on the effects of new mutations and their dependency on the genetic background in which they occur. These two factors can be summarized by the fitness landscape. However, it would require testing all mutations in all backgrounds, making the definition and analysis of fitness landscapes mostly inaccessible. Instead of postulating a particular fitness landscape, we address this problem by considering general classes of landscapes and calculating an upper limit for the time it takes for a population to reach a fitness peak, circumventing the need to have full knowledge about the fitness landscape. We analyze populations in the weak-mutation regime and characterize the conditions that enable them to quickly reach the fitness peak as a function of the number of sites under selection. We show that for additive landscapes there is a critical selection strength enabling populations to reach high-fitness genotypes, regardless of the distribution of effects. This threshold scales with the number of sites under selection, effectively setting a limit to adaptation, and results from the inevitable increase in deleterious mutational pressure as the population adapts in a space of discrete genotypes. Furthermore, we show that for the class of all unimodal landscapes this condition is sufficient but not necessary for rapid adaptation, as in some highly epistatic landscapes the critical strength does not depend on the number of sites under selection; effectively removing this barrier to adaptation.
AU - Heredia, Jorge
AU - Trubenova, Barbora
AU - Sudholt, Dirk
AU - Paixao, Tiago
ID - 1111
IS - 2
JF - Genetics
SN - 00166731
TI - Selection limits to adaptive walks on correlated landscapes
VL - 205
ER -
TY - CONF
AB - There has been renewed interest in modelling the behaviour of evolutionary algorithms by more traditional mathematical objects, such as ordinary differential equations or Markov chains. The advantage is that the analysis becomes greatly facilitated due to the existence of well established methods. However, this typically comes at the cost of disregarding information about the process. Here, we introduce the use of stochastic differential equations (SDEs) for the study of EAs. SDEs can produce simple analytical results for the dynamics of stochastic processes, unlike Markov chains which can produce rigorous but unwieldy expressions about the dynamics. On the other hand, unlike ordinary differential equations (ODEs), they do not discard information about the stochasticity of the process. We show that these are especially suitable for the analysis of fixed budget scenarios and present analogs of the additive and multiplicative drift theorems for SDEs. We exemplify the use of these methods for two model algorithms ((1+1) EA and RLS) on two canonical problems(OneMax and LeadingOnes).
AU - Paixao, Tiago
AU - Pérez Heredia, Jorge
ID - 1112
SN - 978-145034651-1
T2 - Proceedings of the 14th ACM/SIGEVO Conference on Foundations of Genetic Algorithms
TI - An application of stochastic differential equations to evolutionary algorithms
ER -
TY - JOUR
AB - A drawing of a graph G is radial if the vertices of G are placed on concentric circles C 1 , . . . , C k with common center c , and edges are drawn radially : every edge intersects every circle centered at c at most once. G is radial planar if it has a radial embedding, that is, a crossing-free radial drawing. If the vertices of G are ordered or partitioned into ordered levels (as they are for leveled graphs), we require that the assignment of vertices to circles corresponds to the given ordering or leveling. We show that a graph G is radial planar if G has a radial drawing in which every two edges cross an even number of times; the radial embedding has the same leveling as the radial drawing. In other words, we establish the weak variant of the Hanani-Tutte theorem for radial planarity. This generalizes a result by Pach and Toth.
AU - Fulek, Radoslav
AU - Pelsmajer, Michael
AU - Schaefer, Marcus
ID - 1113
IS - 1
JF - Journal of Graph Algorithms and Applications
TI - Hanani-Tutte for radial planarity
VL - 21
ER -
TY - JOUR
AB - Nonequilibrium phase transitions exist in damped-driven open quantum systems when the continuous tuning of an external parameter leads to a transition between two robust steady states. In second-order transitions this change is abrupt at a critical point, whereas in first-order transitions the two phases can coexist in a critical hysteresis domain. Here, we report the observation of a first-order dissipative quantum phase transition in a driven circuit quantum electrodynamics system. It takes place when the photon blockade of the driven cavity-atom system is broken by increasing the drive power. The observed experimental signature is a bimodal phase space distribution with varying weights controlled by the drive strength. Our measurements show an improved stabilization of the classical attractors up to the millisecond range when the size of the quantum system is increased from one to three artificial atoms. The formation of such robust pointer states could be used for new quantum measurement schemes or to investigate multiphoton phases of finite-size, nonlinear, open quantum systems.
AU - Fink, Johannes M
AU - Dombi, András
AU - Vukics, András
AU - Wallraff, Andreas
AU - Domokos, Peter
ID - 1114
IS - 1
JF - Physical Review X
SN - 21603308
TI - Observation of the photon blockade breakdown phase transition
VL - 7
ER -
TY - CONF
AB - Time-triggered switched networks are a deterministic communication infrastructure used by real-time distributed embedded systems. Due to the criticality of the applications running over them, developers need to ensure that end-to-end communication is dependable and predictable. Traditional approaches assume static networks that are not flexible to changes caused by reconfigurations or, more importantly, faults, which are dealt with in the application using redundancy. We adopt the concept of handling faults in the switches from non-real-time networks while maintaining the required predictability.
We study a class of forwarding schemes that can handle various types of failures. We consider probabilistic failures. We study a class of forwarding schemes that can handle various types of failures. We consider probabilistic failures. For a given network with a forwarding scheme and a constant ℓ, we compute the {\em score} of the scheme, namely the probability (induced by faults) that at least ℓ messages arrive on time. We reduce the scoring problem to a reachability problem on a Markov chain with a "product-like" structure. Its special structure allows us to reason about it symbolically, and reduce the scoring problem to #SAT. Our solution is generic and can be adapted to different networks and other contexts. Also, we show the computational complexity of the scoring problem is #P-complete, and we study methods to estimate the score. We evaluate the effectiveness of our techniques with an implementation.
AU - Avni, Guy
AU - Goel, Shubham
AU - Henzinger, Thomas A
AU - Rodríguez Navas, Guillermo
ID - 1116
SN - 03029743
TI - Computing scores of forwarding schemes in switched networks with probabilistic faults
VL - 10206
ER -
TY - JOUR
AB - GABAergic synapses in brain circuits generate inhibitory output signals with submillisecond latency and temporal precision. Whether the molecular identity of the release sensor contributes to these signaling properties remains unclear. Here, we examined the Ca^2+ sensor of exocytosis at GABAergic basket cell (BC) to Purkinje cell (PC) synapses in cerebellum. Immunolabeling suggested that BC terminals selectively expressed synaptotagmin 2 (Syt2), whereas synaptotagmin 1 (Syt1) was enriched in excitatory terminals. Genetic elimination of Syt2 reduced action potential-evoked release to ∼10%, identifying Syt2 as the major Ca^2+ sensor at BC-PC synapses. Differential adenovirus-mediated rescue revealed that Syt2 triggered release with shorter latency and higher temporal precision and mediated faster vesicle pool replenishment than Syt1. Furthermore, deletion of Syt2 severely reduced and delayed disynaptic inhibition following parallel fiber stimulation. Thus, the selective use of Syt2 as release sensor at BC-PC synapses ensures fast and efficient feedforward inhibition in cerebellar microcircuits. #bioimagingfacility-author
AU - Chen, Chong
AU - Arai, Itaru
AU - Satterield, Rachel
AU - Young, Samuel
AU - Jonas, Peter M
ID - 1117
IS - 3
JF - Cell Reports
SN - 22111247
TI - Synaptotagmin 2 is the fast Ca2+ sensor at a central inhibitory synapse
VL - 18
ER -
TY - JOUR
AB - Sharp wave-ripple (SWR) oscillations play a key role in memory consolidation during non-rapid eye movement sleep, immobility, and consummatory behavior. However, whether temporally modulated synaptic excitation or inhibition underlies the ripples is controversial. To address this question, we performed simultaneous recordings of excitatory and inhibitory postsynaptic currents (EPSCs and IPSCs) and local field potentials (LFPs) in the CA1 region of awake mice in vivo. During SWRs, inhibition dominated over excitation, with a peak conductance ratio of 4.1 ± 0.5. Furthermore, the amplitude of SWR-associated IPSCs was positively correlated with SWR magnitude, whereas that of EPSCs was not. Finally, phase analysis indicated that IPSCs were phase-locked to individual ripple cycles, whereas EPSCs were uniformly distributed in phase space. Optogenetic inhibition indicated that PV+ interneurons provided a major contribution to SWR-associated IPSCs. Thus, phasic inhibition, but not excitation, shapes SWR oscillations in the hippocampal CA1 region in vivo.
AU - Gan, Jian
AU - Weng, Shih-Ming
AU - Pernia-Andrade, Alejandro
AU - Csicsvari, Jozsef L
AU - Jonas, Peter M
ID - 1118
IS - 2
JF - Neuron
TI - Phase-locked inhibition, but not excitation, underlies hippocampal ripple oscillations in awake mice in vivo
VL - 93
ER -
TY - JOUR
AB - Understanding the behavior of molecules interacting with superfluid helium represents a formidable challenge and, in general, requires approaches relying on large-scale numerical simulations. Here we demonstrate that experimental data collected over the last 20 years provide evidence that molecules immersed in superfluid helium form recently-predicted angulon quasiparticles [Phys. Rev. Lett. 114, 203001 (2015)]. Most importantly, casting the many-body problem in terms of angulons amounts to a drastic simplification and yields effective molecular moments of inertia as straightforward analytic solutions of a simple microscopic Hamiltonian. The outcome of the angulon theory is in good agreement with experiment for a broad range of molecular impurities, from heavy to medium-mass to light species. These results pave the way to understanding molecular rotation in liquid and crystalline phases in terms of the angulon quasiparticle.
AU - Lemeshko, Mikhail
ID - 1119
IS - 9
JF - Physical Review Letters
SN - 00319007
TI - Quasiparticle approach to molecules interacting with quantum solvents
VL - 118
ER -
TY - JOUR
AB - The existence of a self-localization transition in the polaron problem has been under an active debate ever since Landau suggested it 83 years ago. Here we reveal the self-localization transition for the rotational analogue of the polaron -- the angulon quasiparticle. We show that, unlike for the polarons, self-localization of angulons occurs at finite impurity-bath coupling already at the mean-field level. The transition is accompanied by the spherical-symmetry breaking of the angulon ground state and a discontinuity in the first derivative of the ground-state energy. Moreover, the type of the symmetry breaking is dictated by the symmetry of the microscopic impurity-bath interaction, which leads to a number of distinct self-localized states. The predicted effects can potentially be addressed in experiments on cold molecules trapped in superfluid helium droplets and ultracold quantum gases, as well as on electronic excitations in solids and Bose-Einstein condensates.
AU - Li, Xiang
AU - Seiringer, Robert
AU - Lemeshko, Mikhail
ID - 1120
IS - 3
JF - Physical Review A
SN - 24699926
TI - Angular self-localization of impurities rotating in a bosonic bath
VL - 95
ER -
TY - JOUR
AB - The hippocampus is thought to initiate systems-wide mnemonic processes through the reactivation of previously acquired spatial and episodic memory traces, which can recruit the entorhinal cortex as a first stage of memory redistribution to other brain areas. Hippocampal reactivation occurs during sharp wave-ripples, in which synchronous network firing encodes sequences of places.We investigated the coordination of this replay by recording assembly activity simultaneously in the CA1 region of the hippocampus and superficial layers of the medial entorhinal cortex. We found that entorhinal cell assemblies can replay trajectories independently of the hippocampus and sharp wave-ripples. This suggests that the hippocampus is not the sole initiator of spatial and episodic memory trace reactivation. Memory systems involved in these processes may include nonhierarchical, parallel components.
AU - O'Neill, Joseph
AU - Boccara, Charlotte
AU - Stella, Federico
AU - Schönenberger, Philipp
AU - Csicsvari, Jozsef L
ID - 1132
IS - 6321
JF - Science
SN - 00368075
TI - Superficial layers of the medial entorhinal cortex replay independently of the hippocampus
VL - 355
ER -
TY - JOUR
AB - It is a common knowledge that an effective interaction of a quantum impurity with an electromagnetic field can be screened by surrounding charge carriers, whether mobile or static. Here we demonstrate that very strong, "anomalous" screening can take place in the presence of a neutral, weakly polarizable environment, due to an exchange of orbital angular momentum between the impurity and the bath. Furthermore, we show that it is possible to generalize all phenomena related to isolated impurities in an external field to the case when a many-body environment is present, by casting the problem in terms of the angulon quasiparticle. As a result, the relevant observables such as the effective Rabi frequency, geometric phase, and impurity spatial alignment are straightforward to evaluate in terms of a single parameter: the angular-momentum-dependent screening factor.
AU - Yakaboylu, Enderalp
AU - Lemeshko, Mikhail
ID - 1133
IS - 8
JF - Physical Review Letters
SN - 00319007
TI - Anomalous screening of quantum impurities by a neutral environment
VL - 118
ER -
TY - JOUR
AB - We show that matrix elements of functions of N × N Wigner matrices fluctuate on a scale of order N−1/2 and we identify the limiting fluctuation. Our result holds for any function f of the matrix that has bounded variation thus considerably relaxing the regularity requirement imposed in [7, 11].
AU - Erdös, László
AU - Schröder, Dominik J
ID - 1144
JF - Electronic Communications in Probability
TI - Fluctuations of functions of Wigner matrices
VL - 21
ER -
TY - JOUR
AB - Aim: The present study was to compare the effects of nicotinic acid and nicotinamide on the plasma methyl donors, choline and betaine. Methods: Thirty adult subjects were randomly divided into three groups of equal size, and orally received purified water (C group), nicotinic acid (300 mg, NA group) or nicotinamide (300 mg, NM group). Plasma nicotinamide, N 1-methylnicotinamide, homocysteine, betaine and choline levels before and 1.5-h and 3-h post-dosing, plasma normetanephrine and metanephrine concentrations at 3-h post-dosing, and the urinary excretion of N 1-methyl-2-pyridone-5-carboxamide during the test period were examined. Results: The level of 3-h plasma nicotinamide, N 1-methylnicotinamide, homocysteine, the urinary excretion of N 1-methyl-2-pyridone-5-carboxamide and pulse pressure (PP) in the NM group was 221%, 3972%, 61%, 1728% and 21.2% higher than that of the control group (P < 0.01, except homocysteine and PP P < 0.05), while the 3-h plasma betaine, normetanephrine and metanephrine level in the NM group was 24.4%, 9.4% and 11.7% lower (P < 0.05, except betaine P < 0.01), without significant difference in choline levels. Similar but less pronounced changes were observed in the NA group, with a lower level of 3-h plasma N 1-methylnicotinamide (1.90 ± 0.20 μmol/l vs. 3.62 ± 0.27 μmol/l, P < 0.01) and homocysteine (12.85 ± 1.39 μmol/l vs. 18.08 ± 1.02 μmol/l, P < 0.05) but a higher level of betaine (27.44 ± 0.71 μmol/l vs. 23.52 ± 0.61 μmol/l, P < 0.05) than that of the NM group. Conclusion: The degradation of nicotinamide consumes more betaine than that of nicotinic acid at identical doses. This difference should be taken into consideration in niacin fortification. © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism.
AU - Sun, Wuping
AU - Zhai, Ming-Zhu
AU - Li, Da
AU - Zhou, Yiming
AU - Chen, Nana
AU - Guo, Ming
AU - Zhou, Shisheng
ID - 1146
IS - 4
JF - Clinical Nutrition
TI - Comparison of the effects of nicotinic acid and nicotinamide degradation on plasma betaine and choline levels
VL - 36
ER -
TY - JOUR
AB - We propose a new memetic strategy that can solve the multi-physics, complex inverse problems, formulated as the multi-objective optimization ones, in which objectives are misfits between the measured and simulated states of various governing processes. The multi-deme structure of the strategy allows for both, intensive, relatively cheap exploration with a moderate accuracy and more accurate search many regions of Pareto set in parallel. The special type of selection operator prefers the coherent alternative solutions, eliminating artifacts appearing in the particular processes. The additional accuracy increment is obtained by the parallel convex searches applied to the local scalarizations of the misfit vector. The strategy is dedicated for solving ill-conditioned problems, for which inverting the single physical process can lead to the ambiguous results. The skill of the selection in artifact elimination is shown on the benchmark problem, while the whole strategy was applied for identification of oil deposits, where the misfits are related to various frequencies of the magnetic and electric waves of the magnetotelluric measurements. 2016 Elsevier B.V.
AU - Gajda-Zagorska, Ewa P
AU - Schaefer, Robert
AU - Smołka, Maciej
AU - Pardo, David
AU - Alvarez Aramberri, Julen
ID - 1152
JF - Journal of Computational Science
SN - 18777503
TI - A multi objective memetic inverse solver reinforced by local optimization methods
VL - 18
ER -
TY - THES
AB - This dissertation concerns the automatic verification of probabilistic systems and programs with arrays by statistical and logical methods. Although statistical and logical methods are different in nature, we show that they can be successfully combined for system analysis. In the first part of the dissertation we present a new statistical algorithm for the verification of probabilistic systems with respect to unbounded properties, including linear temporal logic. Our algorithm often performs faster than the previous approaches, and at the same time requires less information about the system. In addition, our method can be generalized to unbounded quantitative properties such as mean-payoff bounds. In the second part, we introduce two techniques for comparing probabilistic systems. Probabilistic systems are typically compared using the notion of equivalence, which requires the systems to have the equal probability of all behaviors. However, this notion is often too strict, since probabilities are typically only empirically estimated, and any imprecision may break the relation between processes. On the one hand, we propose to replace the Boolean notion of equivalence by a quantitative distance of similarity. For this purpose, we introduce a statistical framework for estimating distances between Markov chains based on their simulation runs, and we investigate which distances can be approximated in our framework. On the other hand, we propose to compare systems with respect to a new qualitative logic, which expresses that behaviors occur with probability one or a positive probability. This qualitative analysis is robust with respect to modeling errors and applicable to many domains. In the last part, we present a new quantifier-free logic for integer arrays, which allows us to express counting. Counting properties are prevalent in array-manipulating programs, however they cannot be expressed in the quantified fragments of the theory of arrays. We present a decision procedure for our logic, and provide several complexity results.
AU - Daca, Przemyslaw
ID - 1155
TI - Statistical and logical methods for property checking
ER -
TY - JOUR
AB - Auxin steers numerous physiological processes in plants, making the tight control of its endogenous levels and spatiotemporal distribution a necessity. This regulation is achieved by different mechanisms, including auxin biosynthesis, metabolic conversions, degradation, and transport. Here, we introduce cis-cinnamic acid (c-CA) as a novel and unique addition to a small group of endogenous molecules affecting in planta auxin concentrations. c-CA is the photo-isomerization product of the phenylpropanoid pathway intermediate trans-CA (t-CA). When grown on c-CA-containing medium, an evolutionary diverse set of plant species were shown to exhibit phenotypes characteristic for high auxin levels, including inhibition of primary root growth, induction of root hairs, and promotion of adventitious and lateral rooting. By molecular docking and receptor binding assays, we showed that c-CA itself is neither an auxin nor an anti-auxin, and auxin profiling data revealed that c-CA does not significantly interfere with auxin biosynthesis. Single cell-based auxin accumulation assays showed that c-CA, and not t-CA, is a potent inhibitor of auxin efflux. Auxin signaling reporters detected changes in spatiotemporal distribution of the auxin response along the root of c-CA-treated plants, and long-distance auxin transport assays showed no inhibition of rootward auxin transport. Overall, these results suggest that the phenotypes of c-CA-treated plants are the consequence of a local change in auxin accumulation, induced by the inhibition of auxin efflux. This work reveals a novel mechanism how plants may regulate auxin levels and adds a novel, naturally occurring molecule to the chemical toolbox for the studies of auxin homeostasis.
AU - Steenackers, Ward
AU - Klíma, Petr
AU - Quareshy, Mussa
AU - Cesarino, Igor
AU - Kumpf, Robert
AU - Corneillie, Sander
AU - Araújo, Pedro
AU - Viaene, Tom
AU - Goeminne, Geert
AU - Nowack, Moritz
AU - Ljung, Karin
AU - Friml, Jirí
AU - Blakeslee, Joshua
AU - Novák, Ondřej
AU - Zažímalová, Eva
AU - Napier, Richard
AU - Boerjan, Wout
AU - Vanholme, Bartel
ID - 1159
IS - 1
JF - Plant Physiology
SN - 00320889
TI - Cis-cinnamic acid is a novel natural auxin efflux inhibitor that promotes lateral root formation
VL - 173
ER -
TY - JOUR
AB - We investigate fundamental nonlinear dynamics of ferrofluidic Taylor-Couette flow - flow confined be-tween two concentric independently rotating cylinders - consider small aspect ratio by solving the ferro-hydrodynamical equations, carrying out systematic bifurcation analysis. Without magnetic field, we find steady flow patterns, previously observed with a simple fluid, such as those containing normal one- or two vortex cells, as well as anomalous one-cell and twin-cell flow states. However, when a symmetry-breaking transverse magnetic field is present, all flow states exhibit stimulated, finite two-fold mode. Various bifurcations between steady and unsteady states can occur, corresponding to the transitions between the two-cell and one-cell states. While unsteady, axially oscillating flow states can arise, we also detect the emergence of new unsteady flow states. In particular, we uncover two new states: one contains only the azimuthally oscillating solution in the configuration of the twin-cell flow state, and an-other a rotating flow state. Topologically, these flow states are a limit cycle and a quasiperiodic solution on a two-torus, respectively. Emergence of new flow states in addition to observed ones with classical fluid, indicates that richer but potentially more controllable dynamics in ferrofluidic flows, as such flow states depend on the external magnetic field.
AU - Altmeyer, Sebastian
AU - Do, Younghae
AU - Lai, Ying
ID - 1160
JF - Scientific Reports
SN - 20452322
TI - Dynamics of ferrofluidic flow in the Taylor-Couette system with a small aspect ratio
VL - 7
ER -
TY - JOUR
AB - Coordinated changes of cell shape are often the result of the excitable, wave-like dynamics of the actin cytoskeleton. New work shows that, in migrating cells, protrusion waves arise from mechanochemical crosstalk between adhesion sites, membrane tension and the actin protrusive machinery.
AU - Müller, Jan
AU - Sixt, Michael K
ID - 1161
IS - 1
JF - Current Biology
SN - 09609822
TI - Cell migration: Making the waves
VL - 27
ER -
TY - JOUR
AB - Selected universal experimental properties of high-temperature superconducting (HTS) cuprates have been singled out in the last decade. One of the pivotal challenges in this field is the designation of a consistent interpretation framework within which we can describe quantitatively the universal features of those systems. Here we analyze in a detailed manner the principal experimental data and compare them quantitatively with the approach based on a single-band model of strongly correlated electrons supplemented with strong antiferromagnetic (super)exchange interaction (the so-called t−J−U model). The model rationale is provided by estimating its microscopic parameters on the basis of the three-band approach for the Cu-O plane. We use our original full Gutzwiller wave-function solution by going beyond the renormalized mean-field theory (RMFT) in a systematic manner. Our approach reproduces very well the observed hole doping (δ) dependence of the kinetic-energy gain in the superconducting phase, one of the principal non-Bardeen-Cooper-Schrieffer features of the cuprates. The calculated Fermi velocity in the nodal direction is practically δ-independent and its universal value agrees very well with that determined experimentally. Also, a weak doping dependence of the Fermi wave vector leads to an almost constant value of the effective mass in a pure superconducting phase which is both observed in experiment and reproduced within our approach. An assessment of the currently used models (t−J, Hubbard) is carried out and the results of the canonical RMFT as a zeroth-order solution are provided for comparison to illustrate the necessity of the introduced higher-order contributions.
AU - Spałek, Jozef
AU - Zegrodnik, Michał
AU - Kaczmarczyk, Jan
ID - 1162
IS - 2
JF - Physical Review B - Condensed Matter and Materials Physics
SN - 24699950
TI - Universal properties of high temperature superconductors from real space pairing t-J-U model and its quantitative comparison with experiment
VL - 95
ER -
TY - JOUR
AB - We investigate the effect of the electron-hole (e-h) symmetry breaking on d-wave superconductivity induced by non-local effects of correlations in the generalized Hubbard model. The symmetry breaking is introduced in a two-fold manner: by the next-to-nearest neighbor hopping of electrons and by the charge-bond interaction - the off-diagonal term of the Coulomb potential. Both terms lead to a pronounced asymmetry of the superconducting order parameter. The next-to-nearest neighbor hopping enhances superconductivity for h-doping, while diminishes it for e-doping. The charge-bond interaction alone leads to the opposite effect and, additionally, to the kinetic-energy gain upon condensation in the underdoped regime. With both terms included, with similar amplitudes, the height of the superconducting dome and the critical doping remain in favor of h-doping. The influence of the charge-bond interaction on deviations from symmetry of the shape of the gap at the Fermi surface in the momentum space is briefly discussed.
AU - Wysokiński, Marcin
AU - Kaczmarczyk, Jan
ID - 1163
IS - 8
JF - Journal of Physics: Condensed Matter
SN - 09538984
TI - Unconventional superconductivity in generalized Hubbard model role of electron–hole symmetry breaking terms
VL - 29
ER -
TY - JOUR
AB - Optimum experimental design theory has recently been extended for parameter estimation in copula models. The use of these models allows one to gain in flexibility by considering the model parameter set split into marginal and dependence parameters. However, this separation also leads to the natural issue of estimating only a subset of all model parameters. In this work, we treat this problem with the application of the (Formula presented.)-optimality to copula models. First, we provide an extension of the corresponding equivalence theory. Then, we analyze a wide range of flexible copula models to highlight the usefulness of (Formula presented.)-optimality in many possible scenarios. Finally, we discuss how the usage of the introduced design criterion also relates to the more general issue of copula selection and optimal design for model discrimination.
AU - Perrone, Elisa
AU - Rappold, Andreas
AU - Müller, Werner
ID - 1168
IS - 3
JF - Statistical Methods and Applications
TI - D inf s optimality in copula models
VL - 26
ER -
TY - JOUR
AB - Dispersal is a crucial factor in natural evolution, since it determines the habitat experienced by any population and defines the spatial scale of interactions between individuals. There is compelling evidence for systematic differences in dispersal characteristics within the same population, i.e., genotype-dependent dispersal. The consequences of genotype-dependent dispersal on other evolutionary phenomena, however, are poorly understood. In this article we investigate the effect of genotype-dependent dispersal on spatial gene frequency patterns, using a generalization of the classical diffusion model of selection and dispersal. Dispersal is characterized by the variance of dispersal (diffusion coefficient) and the mean displacement (directional advection term). We demonstrate that genotype-dependent dispersal may change the qualitative behavior of Fisher waves, which change from being “pulled” to being “pushed” wave fronts as the discrepancy in dispersal between genotypes increases. The speed of any wave is partitioned into components due to selection, genotype-dependent variance of dispersal, and genotype-dependent mean displacement. We apply our findings to wave fronts maintained by selection against heterozygotes. Furthermore, we identify a benefit of increased variance of dispersal, quantify its effect on the speed of the wave, and discuss the implications for the evolution of dispersal strategies.
AU - Novak, Sebastian
AU - Kollár, Richard
ID - 1169
IS - 1
JF - Genetics
SN - 00166731
TI - Spatial gene frequency waves under genotype dependent dispersal
VL - 205
ER -
TY - JOUR
AB - We introduce the Voronoi functional of a triangulation of a finite set of points in the Euclidean plane and prove that among all geometric triangulations of the point set, the Delaunay triangulation maximizes the functional. This result neither extends to topological triangulations in the plane nor to geometric triangulations in three and higher dimensions.
AU - Edelsbrunner, Herbert
AU - Glazyrin, Alexey
AU - Musin, Oleg
AU - Nikitenko, Anton
ID - 1173
IS - 5
JF - Combinatorica
SN - 02099683
TI - The Voronoi functional is maximized by the Delaunay triangulation in the plane
VL - 37
ER -
TY - CONF
AB - Security of cryptographic applications is typically defined by security games. The adversary, within certain resources, cannot win with probability much better than 0 (for unpredictability applications, like one-way functions) or much better than 1/2 (indistinguishability applications for instance encryption schemes). In so called squared-friendly applications the winning probability of the adversary, for different values of the application secret randomness, is not only close to 0 or 1/2 on average, but also concentrated in the sense that its second central moment is small. The class of squared-friendly applications, which contains all unpredictability applications and many indistinguishability applications, is particularly important for key derivation. Barak et al. observed that for square-friendly applications one can beat the "RT-bound", extracting secure keys with significantly smaller entropy loss. In turn Dodis and Yu showed that in squared-friendly applications one can directly use a "weak" key, which has only high entropy, as a secure key. In this paper we give sharp lower bounds on square security assuming security for "weak" keys. We show that any application which is either (a) secure with weak keys or (b) allows for entropy savings for keys derived by universal hashing, must be square-friendly. Quantitatively, our lower bounds match the positive results of Dodis and Yu and Barak et al. (TCC\'13, CRYPTO\'11) Hence, they can be understood as a general characterization of squared-friendly applications. While the positive results on squared-friendly applications where derived by one clever application of the Cauchy-Schwarz Inequality, for tight lower bounds we need more machinery. In our approach we use convex optimization techniques and some theory of circular matrices.
AU - Skórski, Maciej
ID - 1174
SN - 18688969
TI - Lower bounds on key derivation for square-friendly applications
VL - 66
ER -
TY - CONF
AB - We study space complexity and time-space trade-offs with a focus not on peak memory usage but on overall memory consumption throughout the computation. Such a cumulative space measure was introduced for the computational model of parallel black pebbling by [Alwen and Serbinenko ’15] as a tool for obtaining results in cryptography. We consider instead the non- deterministic black-white pebble game and prove optimal cumulative space lower bounds and trade-offs, where in order to minimize pebbling time the space has to remain large during a significant fraction of the pebbling. We also initiate the study of cumulative space in proof complexity, an area where other space complexity measures have been extensively studied during the last 10–15 years. Using and extending the connection between proof complexity and pebble games in [Ben-Sasson and Nordström ’08, ’11] we obtain several strong cumulative space results for (even parallel versions of) the resolution proof system, and outline some possible future directions of study of this, in our opinion, natural and interesting space measure.
AU - Alwen, Joel F
AU - De Rezende, Susanna
AU - Nordstrom, Jakob
AU - Vinyals, Marc
ED - Papadimitriou, Christos
ID - 1175
SN - 18688969
TI - Cumulative space in black-white pebbling and resolution
VL - 67
ER -
TY - CONF
AB - The algorithm Argon2i-B of Biryukov, Dinu and Khovratovich is currently being considered by the IRTF (Internet Research Task Force) as a new de-facto standard for password hashing. An older version (Argon2i-A) of the same algorithm was chosen as the winner of the recent Password Hashing Competition. An important competitor to Argon2i-B is the recently introduced Balloon Hashing (BH) algorithm of Corrigan-Gibs, Boneh and Schechter. A key security desiderata for any such algorithm is that evaluating it (even using a custom device) requires a large amount of memory amortized across multiple instances. Alwen and Blocki (CRYPTO 2016) introduced a class of theoretical attacks against Argon2i-A and BH. While these attacks yield large asymptotic reductions in the amount of memory, it was not, a priori, clear if (1) they can be extended to the newer Argon2i-B, (2) the attacks are effective on any algorithm for practical parameter ranges (e.g., 1GB of memory) and (3) if they can be effectively instantiated against any algorithm under realistic hardware constrains. In this work we answer all three of these questions in the affirmative for all three algorithms. This is also the first work to analyze the security of Argon2i-B. In more detail, we extend the theoretical attacks of Alwen and Blocki (CRYPTO 2016) to the recent Argon2i-B proposal demonstrating severe asymptotic deficiencies in its security. Next we introduce several novel heuristics for improving the attack's concrete memory efficiency even when on-chip memory bandwidth is bounded. We then simulate our attacks on randomly sampled Argon2i-A, Argon2i-B and BH instances and measure the resulting memory consumption for various practical parameter ranges and for a variety of upperbounds on the amount of parallelism available to the attacker. Finally we describe, implement, and test a new heuristic for applying the Alwen-Blocki attack to functions employing a technique developed by Corrigan-Gibs et al. for improving concrete security of memory-hard functions. We analyze the collected data and show the effects various parameters have on the memory consumption of the attack. In particular, we can draw several interesting conclusions about the level of security provided by these functions. · For the Alwen-Blocki attack to fail against practical memory parameters, Argon2i-B must be instantiated with more than 10 passes on memory - beyond the "paranoid" parameter setting in the current IRTF proposal. · The technique of Corrigan-Gibs for improving security can also be overcome by the Alwen-Blocki attack under realistic hardware constraints. · On a positive note, both the asymptotic and concrete security of Argon2i-B seem to improve on that of Argon2i-A.
AU - Alwen, Joel F
AU - Blocki, Jeremiah
ID - 1176
SN - 978-150905761-0
TI - Towards practical attacks on Argon2i and balloon hashing
ER -
TY - JOUR
AB - In this article we define an algebraic vertex of a generalized polyhedron and show that the set of algebraic vertices is the smallest set of points needed to define the polyhedron. We prove that the indicator function of a generalized polytope P is a linear combination of indicator functions of simplices whose vertices are algebraic vertices of P. We also show that the indicator function of any generalized polyhedron is a linear combination, with integer coefficients, of indicator functions of cones with apices at algebraic vertices and line-cones. The concept of an algebraic vertex is closely related to the Fourier–Laplace transform. We show that a point v is an algebraic vertex of a generalized polyhedron P if and only if the tangent cone of P, at v, has non-zero Fourier–Laplace transform.
AU - Akopyan, Arseniy
AU - Bárány, Imre
AU - Robins, Sinai
ID - 1180
JF - Advances in Mathematics
SN - 00018708
TI - Algebraic vertices of non-convex polyhedra
VL - 308
ER -
TY - JOUR
AB - We construct efficient authentication protocols and message authentication codes (MACs) whose security can be reduced to the learning parity with noise (LPN) problem. Despite a large body of work—starting with the (Formula presented.) protocol of Hopper and Blum in 2001—until now it was not even known how to construct an efficient authentication protocol from LPN which is secure against man-in-the-middle attacks. A MAC implies such a (two-round) protocol.
AU - Kiltz, Eike
AU - Pietrzak, Krzysztof Z
AU - Venturi, Daniele
AU - Cash, David
AU - Jain, Abhishek
ID - 1187
IS - 4
JF - Journal of Cryptology
TI - Efficient authentication from hard learning problems
VL - 30
ER -
TY - JOUR
AB - Variation in genotypes may be responsible for differences in dispersal rates, directional biases, and growth rates of individuals. These traits may favor certain genotypes and enhance their spatiotemporal spreading into areas occupied by the less advantageous genotypes. We study how these factors influence the speed of spreading in the case of two competing genotypes under the assumption that spatial variation of the total population is small compared to the spatial variation of the frequencies of the genotypes in the population. In that case, the dynamics of the frequency of one of the genotypes is approximately described by a generalized Fisher–Kolmogorov–Petrovskii–Piskunov (F–KPP) equation. This generalized F–KPP equation with (nonlinear) frequency-dependent diffusion and advection terms admits traveling wave solutions that characterize the invasion of the dominant genotype. Our existence results generalize the classical theory for traveling waves for the F–KPP with constant coefficients. Moreover, in the particular case of the quadratic (monostable) nonlinear growth–decay rate in the generalized F–KPP we study in detail the influence of the variance in diffusion and mean displacement rates of the two genotypes on the minimal wave propagation speed.
AU - Kollár, Richard
AU - Novak, Sebastian
ID - 1191
IS - 3
JF - Bulletin of Mathematical Biology
TI - Existence of traveling waves for the generalized F–KPP equation
VL - 79
ER -
TY - CONF
AB - The main result of this paper is a generalization of the classical blossom algorithm for finding perfect matchings. Our algorithm can efficiently solve Boolean CSPs where each variable appears in exactly two constraints (we call it edge CSP) and all constraints are even Δ-matroid relations (represented by lists of tuples). As a consequence of this, we settle the complexity classification of planar Boolean CSPs started by Dvorak and Kupec. Knowing that edge CSP is tractable for even Δ-matroid constraints allows us to extend the tractability result to a larger class of Δ-matroids that includes many classes that were known to be tractable before, namely co-independent, compact, local and binary.
AU - Kazda, Alexandr
AU - Kolmogorov, Vladimir
AU - Rolinek, Michal
ID - 1192
SN - 978-161197478-2
TI - Even delta-matroids and the complexity of planar Boolean CSPs
ER -
TY - CONF
AB - Termination is one of the basic liveness properties, and we study the termination problem for probabilistic programs with real-valued variables. Previous works focused on the qualitative problem that asks whether an input program terminates with probability~1 (almost-sure termination). A powerful approach for this qualitative problem is the notion of ranking supermartingales with respect to a given set of invariants. The quantitative problem (probabilistic termination) asks for bounds on the termination probability. A fundamental and conceptual drawback of the existing approaches to address probabilistic termination is that even though the supermartingales consider the probabilistic behavior of the programs, the invariants are obtained completely ignoring the probabilistic aspect. In this work we address the probabilistic termination problem for linear-arithmetic probabilistic programs with nondeterminism. We define the notion of {\em stochastic invariants}, which are constraints along with a probability bound that the constraints hold. We introduce a concept of {\em repulsing supermartingales}. First, we show that repulsing supermartingales can be used to obtain bounds on the probability of the stochastic invariants. Second, we show the effectiveness of repulsing supermartingales in the following three ways: (1)~With a combination of ranking and repulsing supermartingales we can compute lower bounds on the probability of termination; (2)~repulsing supermartingales provide witnesses for refutation of almost-sure termination; and (3)~with a combination of ranking and repulsing supermartingales we can establish persistence properties of probabilistic programs. We also present results on related computational problems and an experimental evaluation of our approach on academic examples.
AU - Chatterjee, Krishnendu
AU - Novotny, Petr
AU - Zikelic, Djordje
ID - 1194
IS - 1
SN - 07308566
TI - Stochastic invariants for probabilistic termination
VL - 52
ER -
TY - JOUR
AB - We define the . model-measuring problem: given a model . M and specification . ϕ, what is the maximal distance . ρ such that all models . M' within distance . ρ from . M satisfy (or violate) . ϕ. The model-measuring problem presupposes a distance function on models. We concentrate on . automatic distance functions, which are defined by weighted automata. The model-measuring problem subsumes several generalizations of the classical model-checking problem, in particular, quantitative model-checking problems that measure the degree of satisfaction of a specification; robustness problems that measure how much a model can be perturbed without violating the specification; and parameter synthesis for hybrid systems. We show that for automatic distance functions, and (a) . ω-regular linear-time, (b) . ω-regular branching-time, and (c) hybrid specifications, the model-measuring problem can be solved.We use automata-theoretic model-checking methods for model measuring, replacing the emptiness question for word, tree, and hybrid automata by the . optimal-value question for the weighted versions of these automata. For automata over words and trees, we consider weighted automata that accumulate weights by maximizing, summing, discounting, and limit averaging. For hybrid automata, we consider monotonic (parametric) hybrid automata, a hybrid counterpart of (discrete) weighted automata.We give several examples of using the model-measuring problem to compute various notions of robustness and quantitative satisfaction for temporal specifications. Further, we propose the modeling framework for model measuring to ease the specification and reduce the likelihood of errors in modeling.Finally, we present a variant of the model-measuring problem, called the . model-repair problem. The model-repair problem applies to models that do not satisfy the specification; it can be used to derive restrictions, under which the model satisfies the specification, i.e., to repair the model.
AU - Henzinger, Thomas A
AU - Otop, Jan
ID - 1196
JF - Nonlinear Analysis: Hybrid Systems
TI - Model measuring for discrete and hybrid systems
VL - 23
ER -
TY - JOUR
AB - We consider a model of fermions interacting via point interactions, defined via a certain weighted Dirichlet form. While for two particles the interaction corresponds to infinite scattering length, the presence of further particles effectively decreases the interaction strength. We show that the model becomes trivial in the thermodynamic limit, in the sense that the free energy density at any given particle density and temperature agrees with the corresponding expression for non-interacting particles.
AU - Moser, Thomas
AU - Seiringer, Robert
ID - 1198
IS - 3
JF - Letters in Mathematical Physics
SN - 03779017
TI - Triviality of a model of particles with point interactions in the thermodynamic limit
VL - 107
ER -
TY - JOUR
AB - Much of quantitative genetics is based on the ‘infinitesimal model’, under which selection has a negligible effect on the genetic variance. This is typically justified by assuming a very large number of loci with additive effects. However, it applies even when genes interact, provided that the number of loci is large enough that selection on each of them is weak relative to random drift. In the long term, directional selection will change allele frequencies, but even then, the effects of epistasis on the ultimate change in trait mean due to selection may be modest. Stabilising selection can maintain many traits close to their optima, even when the underlying alleles are weakly selected. However, the number of traits that can be optimised is apparently limited to ~4Ne by the ‘drift load’, and this is hard to reconcile with the apparent complexity of many organisms. Just as for the mutation load, this limit can be evaded by a particular form of negative epistasis. A more robust limit is set by the variance in reproductive success. This suggests that selection accumulates information most efficiently in the infinitesimal regime, when selection on individual alleles is weak, and comparable with random drift. A review of evidence on selection strength suggests that although most variance in fitness may be because of alleles with large Nes, substantial amounts of adaptation may be because of alleles in the infinitesimal regime, in which epistasis has modest effects.
AU - Barton, Nicholas H
ID - 1199
JF - Heredity
TI - How does epistasis influence the response to selection?
VL - 118
ER -
TY - JOUR
AB - The eigenvalue distribution of the sum of two large Hermitian matrices, when one of them is conjugated by a Haar distributed unitary matrix, is asymptotically given by the free convolution of their spectral distributions. We prove that this convergence also holds locally in the bulk of the spectrum, down to the optimal scales larger than the eigenvalue spacing. The corresponding eigenvectors are fully delocalized. Similar results hold for the sum of two real symmetric matrices, when one is conjugated by Haar orthogonal matrix.
AU - Bao, Zhigang
AU - Erdös, László
AU - Schnelli, Kevin
ID - 1207
IS - 3
JF - Communications in Mathematical Physics
SN - 00103616
TI - Local law of addition of random matrices on optimal scale
VL - 349
ER -
TY - JOUR
AB - We study parameter estimation in linear Gaussian covariance models, which are p-dimensional Gaussian models with linear constraints on the covariance matrix. Maximum likelihood estimation for this class of models leads to a non-convex optimization problem which typically has many local maxima. Using recent results on the asymptotic distribution of extreme eigenvalues of the Wishart distribution, we provide sufficient conditions for any hill climbing method to converge to the global maximum. Although we are primarily interested in the case in which n≫p, the proofs of our results utilize large sample asymptotic theory under the scheme n/p→γ>1. Remarkably, our numerical simulations indicate that our results remain valid for p as small as 2. An important consequence of this analysis is that, for sample sizes n≃14p, maximum likelihood estimation for linear Gaussian covariance models behaves as if it were a convex optimization problem. © 2016 The Royal Statistical Society and Blackwell Publishing Ltd.
AU - Zwiernik, Piotr
AU - Uhler, Caroline
AU - Richards, Donald
ID - 1208
IS - 4
JF - Journal of the Royal Statistical Society. Series B: Statistical Methodology
SN - 13697412
TI - Maximum likelihood estimation for linear Gaussian covariance models
VL - 79
ER -
TY - JOUR
AB - Systems such as fluid flows in channels and pipes or the complex Ginzburg–Landau system, defined over periodic domains, exhibit both continuous symmetries, translational and rotational, as well as discrete symmetries under spatial reflections or complex conjugation. The simplest, and very common symmetry of this type is the equivariance of the defining equations under the orthogonal group O(2). We formulate a novel symmetry reduction scheme for such systems by combining the method of slices with invariant polynomial methods, and show how it works by applying it to the Kuramoto–Sivashinsky system in one spatial dimension. As an example, we track a relative periodic orbit through a sequence of bifurcations to the onset of chaos. Within the symmetry-reduced state space we are able to compute and visualize the unstable manifolds of relative periodic orbits, their torus bifurcations, a transition to chaos via torus breakdown, and heteroclinic connections between various relative periodic orbits. It would be very hard to carry through such analysis in the full state space, without a symmetry reduction such as the one we present here.
AU - Budanur, Nazmi B
AU - Cvitanović, Predrag
ID - 1211
IS - 3-4
JF - Journal of Statistical Physics
TI - Unstable manifolds of relative periodic orbits in the symmetry reduced state space of the Kuramoto–Sivashinsky system
VL - 167
ER -
TY - JOUR
AB - Bacterial cytokinesis is commonly initiated by the Z-ring, a dynamic cytoskeletal structure that assembles at the site of division. Its primary component is FtsZ, a tubulin-like GTPase, that like its eukaryotic relative forms protein filaments in the presence of GTP. Since the discovery of the Z-ring 25 years ago, various models for the role of FtsZ have been suggested. However, important information about the architecture and dynamics of FtsZ filaments during cytokinesis is still missing. One reason for this lack of knowledge has been the small size of bacteria, which has made it difficult to resolve the orientation and dynamics of individual FtsZ filaments in the Z-ring. While superresolution microscopy experiments have helped to gain more information about the organization of the Z-ring in the dividing cell, they were not yet able to elucidate a mechanism of how FtsZ filaments reorganize during assembly and disassembly of the Z-ring. In this chapter, we explain how to use an in vitro reconstitution approach to investigate the self-organization of FtsZ filaments recruited to a biomimetic lipid bilayer by its membrane anchor FtsA. We show how to perform single-molecule experiments to study the behavior of individual FtsZ monomers during the constant reorganization of the FtsZ-FtsA filament network. We describe how to analyze the dynamics of single molecules and explain why this information can help to shed light onto possible mechanism of Z-ring constriction. We believe that similar experimental approaches will be useful to study the mechanism of membrane-based polymerization of other cytoskeletal systems, not only from prokaryotic but also eukaryotic origin.
AU - Baranova, Natalia
AU - Loose, Martin
ID - 1213
JF - Methods in Cell Biology
SN - 0091679X
TI - Single-molecule measurements to study polymerization dynamics of FtsZ-FtsA copolymers
VL - 137
ER -
TY - JOUR
AB - Since 2006, reprogrammed cells have increasingly been used as a biomedical research technique in addition to neuro-psychiatric methods. These rapidly evolving techniques allow for the generation of neuronal sub-populations, and have sparked interest not only in monogenetic neuro-psychiatric diseases, but also in poly-genetic and poly-aetiological disorders such as schizophrenia (SCZ) and bipolar disorder (BPD). This review provides a summary of 19 publications on reprogrammed adult somatic cells derived from patients with SCZ, and five publications using this technique in patients with BPD. As both disorders are complex and heterogeneous, there is a plurality of hypotheses to be tested in vitro. In SCZ, data on alterations of dopaminergic transmission in vitro are sparse, despite the great explanatory power of the so-called DA hypothesis of SCZ. Some findings correspond to perturbations of cell energy metabolism, and observations in reprogrammed cells suggest neuro-developmental alterations. Some studies also report on the efficacy of medicinal compounds to revert alterations observed in cellular models. However, due to the paucity of replication studies, no comprehensive conclusions can be drawn from studies using reprogrammed cells at the present time. In the future, findings from cell culture methods need to be integrated with clinical, epidemiological, pharmacological and imaging data in order to generate a more comprehensive picture of SCZ and BPD.
AU - Sauerzopf, Ulrich
AU - Sacco, Roberto
AU - Novarino, Gaia
AU - Niello, Marco
AU - Weidenauer, Ana
AU - Praschak Rieder, Nicole
AU - Sitte, Harald
AU - Willeit, Matthaeus
ID - 1228
IS - 1
JF - European Journal of Neuroscience
TI - Are reprogrammed cells a useful tool for studying dopamine dysfunction in psychotic disorders? A review of the current evidence
VL - 45
ER -
TY - JOUR
AB - We study the lengths of curves passing through a fixed number of points on the boundary of a convex shape in the plane. We show that, for any convex shape K, there exist four points on the boundary of K such that the length of any curve passing through these points is at least half of the perimeter of K. It is also shown that the same statement does not remain valid with the additional constraint that the points are extreme points of K. Moreover, the factor ½ cannot be achieved with any fixed number of extreme points. We conclude the paper with a few other inequalities related to the perimeter of a convex shape.
AU - Akopyan, Arseniy
AU - Vysotsky, Vladislav
ID - 909
IS - 7
JF - The American Mathematical Monthly
SN - 00029890
TI - On the lengths of curves passing through boundary points of a planar convex shape
VL - 124
ER -
TY - JOUR
AB - Frequency-independent selection is generally considered as a force that acts to reduce the genetic variation in evolving populations, yet rigorous arguments for this idea are scarce. When selection fluctuates in time, it is unclear whether frequency-independent selection may maintain genetic polymorphism without invoking additional mechanisms. We show that constant frequency-independent selection with arbitrary epistasis on a well-mixed haploid population eliminates genetic variation if we assume linkage equilibrium between alleles. To this end, we introduce the notion of frequency-independent selection at the level of alleles, which is sufficient to prove our claim and contains the notion of frequency-independent selection on haploids. When selection and recombination are weak but of the same order, there may be strong linkage disequilibrium; numerical calculations show that stable equilibria are highly unlikely. Using the example of a diallelic two-locus model, we then demonstrate that frequency-independent selection that fluctuates in time can maintain stable polymorphism if linkage disequilibrium changes its sign periodically. We put our findings in the context of results from the existing literature and point out those scenarios in which the possible role of frequency-independent selection in maintaining genetic variation remains unclear.
AU - Novak, Sebastian
AU - Barton, Nicholas H
ID - 910
IS - 2
JF - Genetics
TI - When does frequency-independent selection maintain genetic variation?
VL - 207
ER -
TY - CONF
AB - We develop a probabilistic technique for colorizing grayscale natural images. In light of the intrinsic uncertainty of this task, the proposed probabilistic framework has numerous desirable properties. In particular, our model is able to produce multiple plausible and vivid colorizations for a given grayscale image and is one of the first colorization models to provide a proper stochastic sampling scheme. Moreover, our training procedure is supported by a rigorous theoretical framework that does not require any ad hoc heuristics and allows for efficient modeling and learning of the joint pixel color distribution.We demonstrate strong quantitative and qualitative experimental results on the CIFAR-10 dataset and the challenging ILSVRC 2012 dataset.
AU - Royer, Amélie
AU - Kolesnikov, Alexander
AU - Lampert, Christoph
ID - 911
TI - Probabilistic image colorization
ER -
TY - JOUR
AB - We consider a many-body system of fermionic atoms interacting via a local pair potential and subject to an external potential within the framework of Bardeen-Cooper-Schrieffer (BCS) theory. We measure the free energy of the whole sample with respect to the free energy of a reference state which allows us to define a BCS functional with boundary conditions at infinity. Our main result is a lower bound for this energy functional in terms of expressions that typically appear in Ginzburg-Landau functionals.
AU - Deuchert, Andreas
ID - 912
IS - 8
JF - Journal of Mathematical Physics
SN - 00222488
TI - A lower bound for the BCS functional with boundary conditions at infinity
VL - 58
ER -
TY - JOUR
AB - Infections with potentially lethal pathogens may negatively affect an individual’s lifespan and decrease its reproductive value. The terminal investment hypothesis predicts that individuals faced with a reduced survival should invest more into reproduction instead of maintenance and growth. Several studies suggest that individuals are indeed able to estimate their body condition and to increase their reproductive effort with approaching death, while other studies gave ambiguous results. We investigate whether queens of a perennial social insect (ant) are able to boost their reproduction following infection with an obligate killing pathogen. Social insect queens are special with regard to reproduction and aging, as they outlive conspecific non-reproductive workers. Moreover, in the ant Cardiocondyla obscurior, fecundity increases with queen age. However, it remained unclear whether this reflects negative reproductive senescence or terminal investment in response to approaching death. Here, we test whether queens of C. obscurior react to infection with the entomopathogenic fungus Metarhizium brunneum by an increased egg-laying rate. We show that a fungal infection triggers a reinforced investment in reproduction in queens. This adjustment of the reproductive rate by ant queens is consistent with predictions of the terminal investment hypothesis and is reported for the first time in a social insect.
AU - Giehr, Julia
AU - Grasse, Anna V
AU - Cremer, Sylvia
AU - Heinze, Jürgen
AU - Schrempf, Alexandra
ID - 914
IS - 7
JF - Royal Society Open Science
SN - 20545703
TI - Ant queens increase their reproductive efforts after pathogen infection
VL - 4
ER -
TY - CONF
AB - We propose a dual decomposition and linear program relaxation of the NP-hard minimum cost multicut problem. Unlike other polyhedral relaxations of the multicut polytope, it is amenable to efficient optimization by message passing. Like other polyhedral relaxations, it can be tightened efficiently by cutting planes. We define an algorithm that alternates between message passing and efficient separation of cycle- and odd-wheel inequalities. This algorithm is more efficient than state-of-the-art algorithms based on linear programming, including algorithms written in the framework of leading commercial software, as we show in experiments with large instances of the problem from applications in computer vision, biomedical image analysis and data mining.
AU - Swoboda, Paul
AU - Andres, Bjoern
ID - 915
SN - 978-153860457-1
TI - A message passing algorithm for the minimum cost multicut problem
VL - 2017
ER -
TY - CONF
AB - We study the quadratic assignment problem, in computer vision also known as graph matching. Two leading solvers for this problem optimize the Lagrange decomposition duals with sub-gradient and dual ascent (also known as message passing) updates. We explore this direction further and propose several additional Lagrangean relaxations of the graph matching problem along with corresponding algorithms, which are all based on a common dual ascent framework. Our extensive empirical evaluation gives several theoretical insights and suggests a new state-of-the-art anytime solver for the considered problem. Our improvement over state-of-the-art is particularly visible on a new dataset with large-scale sparse problem instances containing more than 500 graph nodes each.
AU - Swoboda, Paul
AU - Rother, Carsten
AU - Abu Alhaija, Carsten
AU - Kainmueller, Dagmar
AU - Savchynskyy, Bogdan
ID - 916
SN - 978-153860457-1
TI - A study of lagrangean decompositions and dual ascent solvers for graph matching
VL - 2017
ER -
TY - CONF
AB - We propose a general dual ascent framework for Lagrangean decomposition of combinatorial problems. Although methods of this type have shown their efficiency for a number of problems, so far there was no general algorithm applicable to multiple problem types. In this work, we propose such a general algorithm. It depends on several parameters, which can be used to optimize its performance in each particular setting. We demonstrate efficacy of our method on graph matching and multicut problems, where it outperforms state-of-the-art solvers including those based on subgradient optimization and off-the-shelf linear programming solvers.
AU - Swoboda, Paul
AU - Kuske, Jan
AU - Savchynskyy, Bogdan
ID - 917
SN - 978-153860457-1
TI - A dual ascent framework for Lagrangean decomposition of combinatorial problems
VL - 2017
ER -
TY - THES
AB - The thesis encompasses several topics of plant cell biology which were studied in the model plant Arabidopsis thaliana. Chapter 1 concerns the plant hormone auxin and its polar transport through cells and tissues. The highly controlled, directional transport of auxin is facilitated by plasma membrane-localized transporters. Transporters from the PIN family direct auxin transport due to their polarized localizations at cell membranes. Substantial effort has been put into research on cellular trafficking of PIN proteins, which is thought to underlie their polar distribution. I participated in a forward genetic screen aimed at identifying novel regulators of PIN polarity. The screen yielded several genes which may be involved in PIN polarity regulation or participate in polar auxin transport by other means. Chapter 2 focuses on the endomembrane system, with particular attention to clathrin-mediated endocytosis. The project started with identification of several proteins that interact with clathrin light chains. Among them, I focused on two putative homologues of auxilin, which in non-plant systems is an endocytotic factor known for uncoating clathrin-coated vesicles in the final step of endocytosis. The body of my work consisted of an in-depth characterization of transgenic A. thaliana lines overexpressing these putative auxilins in an inducible manner. Overexpression of these proteins leads to an inhibition of endocytosis, as documented by imaging of cargoes and clathrin-related endocytic machinery. An extension of this work is an investigation into a concept of homeostatic regulation acting between distinct transport processes in the endomembrane system. With auxilin overexpressing lines, where endocytosis is blocked specifically, I made observations on the mutual relationship between two opposite trafficking processes of secretion and endocytosis. In Chapter 3, I analyze cortical microtubule arrays and their relationship to auxin signaling and polarized growth in elongating cells. In plants, microtubules are organized into arrays just below the plasma membrane, and it is thought that their function is to guide membrane-docked cellulose synthase complexes. These, in turn, influence cell wall structure and cell shape by directed deposition of cellulose fibres. In elongating cells, cortical microtubule arrays are able to reorient in relation to long cell axis, and these reorientations have been linked to cell growth and to signaling of growth-regulating factors such as auxin or light. In this chapter, I am addressing the causal relationship between microtubule array reorientation, growth, and auxin signaling. I arrive at a model where array reorientation is not guided by auxin directly, but instead is only controlled by growth, which, in turn, is regulated by auxin.
AU - Adamowski, Maciek
ID - 938
TI - Investigations into cell polarity and trafficking in the plant model Arabidopsis thaliana
ER -
TY - JOUR
AB - We reveal the existence of continuous families of guided single-mode solitons in planar waveguides with weakly nonlinear active core and absorbing boundaries. Stable propagation of TE and TM-polarized solitons is accompanied by attenuation of all other modes, i.e., the waveguide features properties of conservative and dissipative systems. If the linear spectrum of the waveguide possesses exceptional points, which occurs in the case of TM polarization, an originally focusing (defocusing) material nonlinearity may become effectively defocusing (focusing). This occurs due to the geometric phase of the carried eigenmode when the surface impedance encircles the exceptional point. In its turn, the change of the effective nonlinearity ensures the existence of dark (bright) solitons in spite of focusing (defocusing) Kerr nonlinearity of the core. The existence of an exceptional point can also result in anomalous enhancement of the effective nonlinearity. In terms of practical applications, the nonlinearity of the reported waveguide can be manipulated by controlling the properties of the absorbing cladding.
AU - Midya, Bikashkali
AU - Konotop, Vladimir
ID - 939
IS - 3
JF - Physical Review Letters
SN - 00319007
TI - Waveguides with absorbing boundaries: Nonlinearity controlled by an exceptional point and solitons
VL - 119
ER -
TY - CONF
AB - Recently there has been a proliferation of automated program repair (APR) techniques, targeting various programming languages. Such techniques can be generally classified into two families: syntactic- and semantics-based. Semantics-based APR, on which we focus, typically uses symbolic execution to infer semantic constraints and then program synthesis to construct repairs conforming to them. While syntactic-based APR techniques have been shown successful on bugs in real-world programs written in both C and Java, semantics-based APR techniques mostly target C programs. This leaves empirical comparisons of the APR families not fully explored, and developers without a Java-based semantics APR technique. We present JFix, a semantics-based APR framework that targets Java, and an associated Eclipse plugin. JFix is implemented atop Symbolic PathFinder, a well-known symbolic execution engine for Java programs. It extends one particular APR technique (Angelix), and is designed to be sufficiently generic to support a variety of such techniques. We demonstrate that semantics-based APR can indeed efficiently and effectively repair a variety of classes of bugs in large real-world Java programs. This supports our claim that the framework can both support developers seeking semantics-based repair of bugs in Java programs, as well as enable larger scale empirical studies comparing syntactic- and semantics-based APR targeting Java. The demonstration of our tool is available via the project website at: https://xuanbachle.github.io/semanticsrepair/
AU - Le, Xuan
AU - Chu, Duc Hiep
AU - Lo, David
AU - Le Goues, Claire
AU - Visser, Willem
ID - 941
T2 - Proceedings of the 26th ACM SIGSOFT International Symposium on Software Testing and Analysis
TI - JFIX: Semantics-based repair of Java programs via symbolic PathFinder
ER -
TY - CONF
AB - A notable class of techniques for automatic program repair is known as semantics-based. Such techniques, e.g., Angelix, infer semantic specifications via symbolic execution, and then use program synthesis to construct new code that satisfies those inferred specifications. However, the obtained specifications are naturally incomplete, leaving the synthesis engine with a difficult task of synthesizing a general solution from a sparse space of many possible solutions that are consistent with the provided specifications but that do not necessarily generalize. We present S3, a new repair synthesis engine that leverages programming-by-examples methodology to synthesize high-quality bug repairs. The novelty in S3 that allows it to tackle the sparse search space to create more general repairs is three-fold: (1) A systematic way to customize and constrain the syntactic search space via a domain-specific language, (2) An efficient enumeration-based search strategy over the constrained search space, and (3) A number of ranking features based on measures of the syntactic and semantic distances between candidate solutions and the original buggy program. We compare S3’s repair effectiveness with state-of-the-art synthesis engines Angelix, Enumerative, and CVC4. S3 can successfully and correctly fix at least three times more bugs than the best baseline on datasets of 52 bugs in small programs, and 100 bugs in real-world large programs.
AU - Le, Xuan
AU - Chu, Duc Hiep
AU - Lo, David
AU - Le Goues, Claire
AU - Visser, Willem
ID - 942
SN - 978-145035105-8
TI - S3: Syntax- and semantic-guided repair synthesis via programming by examples
VL - F130154
ER -
TY - JOUR
AB - Like many developing tissues, the vertebrate neural tube is patterned by antiparallel morphogen gradients. To understand how these inputs are interpreted, we measured morphogen signaling and target gene expression in mouse embryos and chick ex vivo assays. From these data, we derived and validated a characteristic decoding map that relates morphogen input to the positional identity of neural progenitors. Analysis of the observed responses indicates that the underlying interpretation strategy minimizes patterning errors in response to the joint input of noisy opposing gradients. We reverse-engineered a transcriptional network that provides a mechanistic basis for the observed cell fate decisions and accounts for the precision and dynamics of pattern formation. Together, our data link opposing gradient dynamics in a growing tissue to precise pattern formation.
AU - Zagórski, Marcin P
AU - Tabata, Yoji
AU - Brandenberg, Nathalie
AU - Lutolf, Matthias
AU - Tkacik, Gasper
AU - Bollenbach, Tobias
AU - Briscoe, James
AU - Kicheva, Anna
ID - 943
IS - 6345
JF - Science
SN - 00368075
TI - Decoding of position in the developing neural tube from antiparallel morphogen gradients
VL - 356
ER -
TY - JOUR
AB - The concerted production of neurons and glia by neural stem cells (NSCs) is essential for neural circuit assembly. In the developing cerebral cortex, radial glia progenitors (RGPs) generate nearly all neocortical neurons and certain glia lineages. RGP proliferation behavior shows a high degree of non-stochasticity, thus a deterministic characteristic of neuron and glia production. However, the cellular and molecular mechanisms controlling RGP behavior and proliferation dynamics in neurogenesis and glia generation remain unknown. By using mosaic analysis with double markers (MADM)-based genetic paradigms enabling the sparse and global knockout with unprecedented single-cell resolution, we identified Lgl1 as a critical regulatory component. We uncover Lgl1-dependent tissue-wide community effects required for embryonic cortical neurogenesis and novel cell-autonomous Lgl1 functions controlling RGP-mediated glia genesis and postnatal NSC behavior. These results suggest that NSC-mediated neuron and glia production is tightly regulated through the concerted interplay of sequential Lgl1-dependent global and cell intrinsic mechanisms.
AU - Beattie, Robert J
AU - Postiglione, Maria P
AU - Burnett, Laura
AU - Laukoter, Susanne
AU - Streicher, Carmen
AU - Pauler, Florian
AU - Xiao, Guanxi
AU - Klezovitch, Olga
AU - Vasioukhin, Valeri
AU - Ghashghaei, Troy
AU - Hippenmeyer, Simon
ID - 944
IS - 3
JF - Neuron
SN - 08966273
TI - Mosaic analysis with double markers reveals distinct sequential functions of Lgl1 in neural stem cells
VL - 94
ER -
TY - JOUR
AB - While chromosome-wide dosage compensation of the X chromosome has been found in many species, studies in ZW clades have indicated that compensation of the Z is more localized and/or incomplete. In the ZW Lepidoptera, some species show complete compensation of the Z chromosome, while others lack full equalization, but what drives these inconsistencies is unclear. Here, we compare patterns of male and female gene expression on the Z chromosome of two closely related butterfly species, Papilio xuthus and Papilio machaon, and in multiple tissues of two moths species, Plodia interpunctella and Bombyx mori, which were previously found to differ in the extent to which they equalize Z-linked gene expression between the sexes. We find that, while some species and tissues seem to have incomplete dosage compensation, this is in fact due to the accumulation of male-biased genes and the depletion of female-biased genes on the Z chromosome. Once this is accounted for, the Z chromosome is fully compensated in all four species, through the up-regulation of Z expression in females and in some cases additional down-regulation in males. We further find that both sex-biased genes and Z-linked genes have increased rates of expression divergence in this clade, and that this can lead to fast shifts in patterns of gene expression even between closely related species. Taken together, these results show that the uneven distribution of sex-biased genes on sex chromosomes can confound conclusions about dosage compensation and that Z chromosome-wide dosage compensation is not only possible but ubiquitous among Lepidoptera.
AU - Huylmans, Ann K
AU - Macon, Ariana
AU - Vicoso, Beatriz
ID - 945
IS - 10
JF - Molecular Biology and Evolution
SN - 07374038
TI - Global dosage compensation is ubiquitous in Lepidoptera, but counteracted by the masculinization of the Z chromosome
VL - 34
ER -
TY - JOUR
AB - Roots navigate through soil integrating environmental signals to orient their growth. The Arabidopsis root is a widely used model for developmental, physiological and cell biological studies. Live imaging greatly aids these efforts, but the horizontal sample position and continuous root tip displacement present significant difficulties. Here, we develop a confocal microscope setup for vertical sample mounting and integrated directional illumination. We present TipTracker – a custom software for automatic tracking of diverse moving objects usable on various microscope setups. Combined, this enables observation of root tips growing along the natural gravity vector over prolonged periods of time, as well as the ability to induce rapid gravity or light stimulation. We also track migrating cells in the developing zebrafish embryo, demonstrating the utility of this system in the acquisition of high-resolution data sets of dynamic samples. We provide detailed descriptions of the tools enabling the easy implementation on other microscopes.
AU - Von Wangenheim, Daniel
AU - Hauschild, Robert
AU - Fendrych, Matyas
AU - Barone, Vanessa
AU - Benková, Eva
AU - Friml, Jirí
ID - 946
JF - eLife
TI - Live tracking of moving samples in confocal microscopy for vertically grown roots
VL - 6
ER -
TY - JOUR
AB - Viewing the ways a living cell can organize its metabolism as the phase space of a physical system, regulation can be seen as the ability to reduce the entropy of that space by selecting specific cellular configurations that are, in some sense, optimal. Here we quantify the amount of regulation required to control a cell's growth rate by a maximum-entropy approach to the space of underlying metabolic phenotypes, where a configuration corresponds to a metabolic flux pattern as described by genome-scale models. We link the mean growth rate achieved by a population of cells to the minimal amount of metabolic regulation needed to achieve it through a phase diagram that highlights how growth suppression can be as costly (in regulatory terms) as growth enhancement. Moreover, we provide an interpretation of the inverse temperature β controlling maximum-entropy distributions based on the underlying growth dynamics. Specifically, we show that the asymptotic value of β for a cell population can be expected to depend on (i) the carrying capacity of the environment, (ii) the initial size of the colony, and (iii) the probability distribution from which the inoculum was sampled. Results obtained for E. coli and human cells are found to be remarkably consistent with empirical evidence.
AU - De Martino, Daniele
AU - Capuani, Fabrizio
AU - De Martino, Andrea
ID - 947
IS - 1
JF - Physical Review E Statistical Nonlinear and Soft Matter Physics
SN - 24700045
TI - Quantifying the entropic cost of cellular growth control
VL - 96
ER -
TY - CONF
AB - Two-player games on graphs are widely studied in formal methods as they model the interaction between a system and its environment. The game is played by moving a token throughout a graph to produce an infinite path. There are several common modes to determine how the players move the token through the graph; e.g., in turn-based games the players alternate turns in moving the token. We study the bidding mode of moving the token, which, to the best of our knowledge, has never been studied in infinite-duration games. Both players have separate budgets, which sum up to $1$. In each turn, a bidding takes place. Both players submit bids simultaneously, and a bid is legal if it does not exceed the available budget. The winner of the bidding pays his bid to the other player and moves the token. For reachability objectives, repeated bidding games have been studied and are called Richman games. There, a central question is the existence and computation of threshold budgets; namely, a value t\in [0,1] such that if\PO's budget exceeds $t$, he can win the game, and if\PT's budget exceeds 1-t, he can win the game. We focus on parity games and mean-payoff games. We show the existence of threshold budgets in these games, and reduce the problem of finding them to Richman games. We also determine the strategy-complexity of an optimal strategy. Our most interesting result shows that memoryless strategies suffice for mean-payoff bidding games.
AU - Avni, Guy
AU - Henzinger, Thomas A
AU - Chonev, Ventsislav K
ID - 950
SN - 1868-8969
TI - Infinite-duration bidding games
VL - 85
ER -
TY - JOUR
AB - Dengue-suppressing Wolbachia strains are promising tools for arbovirus control, particularly as they have the potential to self-spread following local introductions. To test this, we followed the frequency of the transinfected Wolbachia strain wMel through Ae. aegypti in Cairns, Australia, following releases at 3 nonisolated locations within the city in early 2013. Spatial spread was analysed graphically using interpolation and by fitting a statistical model describing the position and width of the wave. For the larger 2 of the 3 releases (covering 0.97 km2 and 0.52 km2), we observed slow but steady spatial spread, at about 100–200 m per year, roughly consistent with theoretical predictions. In contrast, the smallest release (0.11 km2) produced erratic temporal and spatial dynamics, with little evidence of spread after 2 years. This is consistent with the prediction concerning fitness-decreasing Wolbachia transinfections that a minimum release area is needed to achieve stable local establishment and spread in continuous habitats. Our graphical and likelihood analyses produced broadly consistent estimates of wave speed and wave width. Spread at all sites was spatially heterogeneous, suggesting that environmental heterogeneity will affect large-scale Wolbachia transformations of urban mosquito populations. The persistence and spread of Wolbachia in release areas meeting minimum area requirements indicates the promise of successful large-scale population transfo
AU - Schmidt, Tom
AU - Barton, Nicholas H
AU - Rasic, Gordana
AU - Turley, Andrew
AU - Montgomery, Brian
AU - Iturbe Ormaetxe, Inaki
AU - Cook, Peter
AU - Ryan, Peter
AU - Ritchie, Scott
AU - Hoffmann, Ary
AU - O’Neill, Scott
AU - Turelli, Michael
ID - 951
IS - 5
JF - PLoS Biology
SN - 15449173
TI - Local introduction and heterogeneous spatial spread of dengue-suppressing Wolbachia through an urban population of Aedes Aegypti
VL - 15
ER -
TY - JOUR
AB - A novel strategy for controlling the spread of arboviral diseases such as dengue, Zika and chikungunya is to transform mosquito populations with virus-suppressing Wolbachia. In general, Wolbachia transinfected into mosquitoes induce fitness costs through lower viability or fecundity. These maternally inherited bacteria also produce a frequency-dependent advantage for infected females by inducing cytoplasmic incompatibility (CI), which kills the embryos produced by uninfected females mated to infected males. These competing effects, a frequency-dependent advantage and frequency-independent costs, produce bistable Wolbachia frequency dynamics. Above a threshold frequency, denoted pˆ, CI drives fitness-decreasing Wolbachia transinfections through local populations; but below pˆ, infection frequencies tend to decline to zero. If pˆ is not too high, CI also drives spatial spread once infections become established over sufficiently large areas. We illustrate how simple models provide testable predictions concerning the spatial and temporal dynamics of Wolbachia introductions, focusing on rate of spatial spread, the shape of spreading waves, and the conditions for initiating spread from local introductions. First, we consider the robustness of diffusion-based predictions to incorporating two important features of wMel-Aedes aegypti biology that may be inconsistent with the diffusion approximations, namely fast local dynamics induced by complete CI (i.e., all embryos produced from incompatible crosses die) and long-tailed, non-Gaussian dispersal. With complete CI, our numerical analyses show that long-tailed dispersal changes wave-width predictions only slightly; but it can significantly reduce wave speed relative to the diffusion prediction; it also allows smaller local introductions to initiate spatial spread. Second, we use approximations for pˆ and dispersal distances to predict the outcome of 2013 releases of wMel-infected Aedes aegypti in Cairns, Australia, Third, we describe new data from Ae. aegypti populations near Cairns, Australia that demonstrate long-distance dispersal and provide an approximate lower bound on pˆ for wMel in northeastern Australia. Finally, we apply our analyses to produce operational guidelines for efficient transformation of vector populations over large areas. We demonstrate that even very slow spatial spread, on the order of 10-20 m/month (as predicted), can produce area-wide population transformation within a few years following initial releases covering about 20-30% of the target area.
AU - Turelli, Michael
AU - Barton, Nicholas H
ID - 952
JF - Theoretical Population Biology
SN - 00405809
TI - Deploying dengue-suppressing Wolbachia: Robust models predict slow but effective spatial spread in Aedes aegypti
VL - 115
ER -
TY - JOUR
AB - The role of natural selection in the evolution of adaptive phenotypes has undergone constant probing by evolutionary biologists, employing both theoretical and empirical approaches. As Darwin noted, natural selection can act together with other processes, including random changes in the frequencies of phenotypic differences that are not under strong selection, and changes in the environment, which may reflect evolutionary changes in the organisms themselves. As understanding of genetics developed after 1900, the new genetic discoveries were incorporated into evolutionary biology. The resulting general principles were summarized by Julian Huxley in his 1942 book Evolution: the modern synthesis. Here, we examine how recent advances in genetics, developmental biology and molecular biology, including epigenetics, relate to today's understanding of the evolution of adaptations. We illustrate how careful genetic studies have repeatedly shown that apparently puzzling results in a wide diversity of organisms involve processes that are consistent with neo-Darwinism. They do not support important roles in adaptation for processes such as directed mutation or the inheritance of acquired characters, and therefore no radical revision of our understanding of the mechanism of adaptive evolution is needed.
AU - Charlesworth, Deborah
AU - Barton, Nicholas H
AU - Charlesworth, Brian
ID - 953
IS - 1855
JF - Proceedings of the Royal Society of London Series B Biological Sciences
TI - The sources of adaptive evolution
VL - 284
ER -
TY - JOUR
AB - Understanding the relation between genotype and phenotype remains a major challenge. The difficulty of predicting individual mutation effects, and particularly the interactions between them, has prevented the development of a comprehensive theory that links genotypic changes to their phenotypic effects. We show that a general thermodynamic framework for gene regulation, based on a biophysical understanding of protein-DNA binding, accurately predicts the sign of epistasis in a canonical cis-regulatory element consisting of overlapping RNA polymerase and repressor binding sites. Sign and magnitude of individual mutation effects are sufficient to predict the sign of epistasis and its environmental dependence. Thus, the thermodynamic model offers the correct null prediction for epistasis between mutations across DNA-binding sites. Our results indicate that a predictive theory for the effects of cis-regulatory mutations is possible from first principles, as long as the essential molecular mechanisms and the constraints these impose on a biological system are accounted for.
AU - Lagator, Mato
AU - Paixao, Tiago
AU - Barton, Nicholas H
AU - Bollback, Jonathan P
AU - Guet, Calin C
ID - 954
JF - eLife
SN - 2050084X
TI - On the mechanistic nature of epistasis in a canonical cis-regulatory element
VL - 6
ER -
TY - JOUR
AB - Gene expression is controlled by networks of regulatory proteins that interact specifically with external signals and DNA regulatory sequences. These interactions force the network components to co-evolve so as to continually maintain function. Yet, existing models of evolution mostly focus on isolated genetic elements. In contrast, we study the essential process by which regulatory networks grow: the duplication and subsequent specialization of network components. We synthesize a biophysical model of molecular interactions with the evolutionary framework to find the conditions and pathways by which new regulatory functions emerge. We show that specialization of new network components is usually slow, but can be drastically accelerated in the presence of regulatory crosstalk and mutations that promote promiscuous interactions between network components.
AU - Friedlander, Tamar
AU - Prizak, Roshan
AU - Barton, Nicholas H
AU - Tkacik, Gasper
ID - 955
IS - 1
JF - Nature Communications
SN - 20411723
TI - Evolution of new regulatory functions on biophysically realistic fitness landscapes
VL - 8
ER -
TY - JOUR
AB - We study a class of ergodic quantum Markov semigroups on finite-dimensional unital C⁎-algebras. These semigroups have a unique stationary state σ, and we are concerned with those that satisfy a quantum detailed balance condition with respect to σ. We show that the evolution on the set of states that is given by such a quantum Markov semigroup is gradient flow for the relative entropy with respect to σ in a particular Riemannian metric on the set of states. This metric is a non-commutative analog of the 2-Wasserstein metric, and in several interesting cases we are able to show, in analogy with work of Otto on gradient flows with respect to the classical 2-Wasserstein metric, that the relative entropy is strictly and uniformly convex with respect to the Riemannian metric introduced here. As a consequence, we obtain a number of new inequalities for the decay of relative entropy for ergodic quantum Markov semigroups with detailed balance.
AU - Carlen, Eric
AU - Maas, Jan
ID - 956
IS - 5
JF - Journal of Functional Analysis
SN - 00221236
TI - Gradient flow and entropy inequalities for quantum Markov semigroups with detailed balance
VL - 273
ER -
TY - CHAP
AB - Small molecule biosensors based on Forster resonance energy transfer (FRET) enable small molecule signaling to be monitored with high spatial and temporal resolution in complex cellular environments. FRET sensors can be constructed by fusing a pair of fluorescent proteins to a suitable recognition domain, such as a member of the solute-binding protein (SBP) superfamily. However, naturally occurring SBPs may be unsuitable for incorporation into FRET sensors due to their low thermostability, which may preclude imaging under physiological conditions, or because the positions of their N- and C-termini may be suboptimal for fusion of fluorescent proteins, which may limit the dynamic range of the resulting sensors. Here, we show how these problems can be overcome using ancestral protein reconstruction and circular permutation. Ancestral protein reconstruction, used as a protein engineering strategy, leverages phylogenetic information to improve the thermostability of proteins, while circular permutation enables the termini of an SBP to be repositioned to maximize the dynamic range of the resulting FRET sensor. We also provide a protocol for cloning the engineered SBPs into FRET sensor constructs using Golden Gate assembly and discuss considerations for in situ characterization of the FRET sensors.
AU - Clifton, Ben
AU - Whitfield, Jason
AU - Sanchez Romero, Inmaculada
AU - Herde, Michel
AU - Henneberger, Christian
AU - Janovjak, Harald L
AU - Jackson, Colin
ED - Stein, Viktor
ID - 957
SN - 10643745
T2 - Synthetic Protein Switches
TI - Ancestral protein reconstruction and circular permutation for improving the stability and dynamic range of FRET sensors
VL - 1596
ER -
TY - CHAP
AB - Biosensors that exploit Forster resonance energy transfer (FRET) can be used to visualize biological and physiological processes and are capable of providing detailed information in both spatial and temporal dimensions. In a FRET-based biosensor, substrate binding is associated with a change in the relative positions of two fluorophores, leading to a change in FRET efficiency that may be observed in the fluorescence spectrum. As a result, their design requires a ligand-binding protein that exhibits a conformational change upon binding. However, not all ligand-binding proteins produce responsive sensors upon conjugation to fluorescent proteins or dyes, and identifying the optimum locations for the fluorophores often involves labor-intensive iterative design or high-throughput screening. Combining the genetic fusion of a fluorescent protein to the ligand-binding protein with site-specific covalent attachment of a fluorescent dye can allow fine control over the positions of the two fluorophores, allowing the construction of very sensitive sensors. This relies upon the accurate prediction of the locations of the two fluorophores in bound and unbound states. In this chapter, we describe a method for computational identification of dye-attachment sites that allows the use of cysteine modification to attach synthetic dyes that can be paired with a fluorescent protein for the purposes of creating FRET sensors.
AU - Mitchell, Joshua
AU - Zhang, William
AU - Herde, Michel
AU - Henneberger, Christian
AU - Janovjak, Harald L
AU - O'Mara, Megan
AU - Jackson, Colin
ED - Stein, Viktor
ID - 958
SN - 10643745
T2 - Synthetic Protein Switches
TI - Method for developing optical sensors using a synthetic dye fluorescent protein FRET pair and computational modeling and assessment
VL - 1596
ER -
TY - JOUR
AB - In this work it is shown that scale-free tails in metabolic flux distributions inferred in stationary models are an artifact due to reactions involved in thermodynamically unfeasible cycles, unbounded by physical constraints and in principle able to perform work without expenditure of free energy. After implementing thermodynamic constraints by removing such loops, metabolic flux distributions scale meaningfully with the physical limiting factors, acquiring in turn a richer multimodal structure potentially leading to symmetry breaking while optimizing for objective functions.
AU - De Martino, Daniele
ID - 959
IS - 6
JF - Physical Review E Statistical Nonlinear and Soft Matter Physics
SN - 24700045
TI - Scales and multimodal flux distributions in stationary metabolic network models via thermodynamics
VL - 95
ER -
TY - JOUR
AB - The human cerebral cortex is the seat of our cognitive abilities and composed of an extraordinary number of neurons, organized in six distinct layers. The establishment of specific morphological and physiological features in individual neurons needs to be regulated with high precision. Impairments in the sequential developmental programs instructing corticogenesis lead to alterations in the cortical cytoarchitecture which is thought to represent the major underlying cause for several neurological disorders including neurodevelopmental and psychiatric diseases. In this review we discuss the role of cell polarity at sequential stages during cortex development. We first provide an overview of morphological cell polarity features in cortical neural stem cells and newly-born postmitotic neurons. We then synthesize a conceptual molecular and biochemical framework how cell polarity is established at the cellular level through a break in symmetry in nascent cortical projection neurons. Lastly we provide a perspective how the molecular mechanisms applying to single cells could be probed and integrated in an in vivo and tissue-wide context.
AU - Hansen, Andi H
AU - Düllberg, Christian F
AU - Mieck, Christine
AU - Loose, Martin
AU - Hippenmeyer, Simon
ID - 960
JF - Frontiers in Cellular Neuroscience
SN - 16625102
TI - Cell polarity in cerebral cortex development - cellular architecture shaped by biochemical networks
VL - 11
ER -
TY - THES
AB - Cell-cell contact formation constitutes the first step in the emergence of multicellularity in evolution, thereby allowing the differentiation of specialized cell types. In metazoan development, cell-cell contact formation is thought to influence cell fate specification, and cell fate specification has been implicated in cell-cell contact formation. However, remarkably little is yet known about whether and how the interaction and feedback between cell-cell contact formation and cell fate specification affect development. Here we identify a positive feedback loop between cell-cell contact duration, morphogen signaling and mesendoderm cell fate specification during zebrafish gastrulation. We show that long lasting cell-cell contacts enhance the competence of prechordal plate (ppl) progenitor cells to respond to Nodal signaling, required for proper ppl cell fate specification. We further show that Nodal signalling romotes ppl cell-cell contact duration, thereby generating an effective positive feedback loop between ppl cell-cell contact duration and cell fate specification. Finally, by using a combination of theoretical modeling and experimentation, we show that this feedback loop determines whether anterior axial mesendoderm cells become ppl progenitors or, instead, turn into endoderm progenitors. Our findings reveal that the gene regulatory networks leading to cell fate diversification within the developing embryo are controlled by the interdependent activities of cell-cell signaling and contact formation.
AU - Barone, Vanessa
ID - 961
TI - Cell adhesion and cell fate: An effective feedback loop during zebrafish gastrulation
ER -
TY - CONF
AB - We present a new algorithm for model counting of a class of string constraints. In addition to the classic operation of concatenation, our class includes some recursively defined operations such as Kleene closure, and replacement of substrings. Additionally, our class also includes length constraints on the string expressions, which means, by requiring reasoning about numbers, that we face a multi-sorted logic. In the end, our string constraints are motivated by their use in programming for web applications. Our algorithm comprises two novel features: the ability to use a technique of (1) partial derivatives for constraints that are already in a solved form, i.e. a form where its (string) satisfiability is clearly displayed, and (2) non-progression, where cyclic reasoning in the reduction process may be terminated (thus allowing for the algorithm to look elsewhere). Finally, we experimentally compare our model counter with two recent works on model counting of similar constraints, SMC [18] and ABC [5], to demonstrate its superior performance.
AU - Trinh, Minh
AU - Chu, Duc Hiep
AU - Jaffar, Joxan
ED - Majumdar, Rupak
ED - Kunčak, Viktor
ID - 962
SN - 03029743
TI - Model counting for recursively-defined strings
VL - 10427
ER -
TY - CONF
AB - Network games are widely used as a model for selfish resource-allocation problems. In the classical model, each player selects a path connecting her source and target vertex. The cost of traversing an edge depends on the number of players that traverse it. Thus, it abstracts the fact that different users may use a resource at different times and for different durations, which plays an important role in defining the costs of the users in reality. For example, when transmitting packets in a communication network, routing traffic in a road network, or processing a task in a production system, the traversal of the network involves an inherent delay, and so sharing and congestion of resources crucially depends on time. We study timed network games , which add a time component to network games. Each vertex v in the network is associated with a cost function, mapping the load on v to the price that a player pays for staying in v for one time unit with this load. In addition, each edge has a guard, describing time intervals in which the edge can be traversed, forcing the players to spend time on vertices. Unlike earlier work that add a time component to network games, the time in our model is continuous and cannot be discretized. In particular, players have uncountably many strategies, and a game may have uncountably many pure Nash equilibria. We study properties of timed network games with cost-sharing or congestion cost functions: their stability, equilibrium inefficiency, and complexity. In particular, we show that the answer to the question whether we can restrict attention to boundary strategies, namely ones in which edges are traversed only at the boundaries of guards, is mixed.
AU - Avni, Guy
AU - Guha, Shibashis
AU - Kupferman, Orna
ID - 963
SN - 18688969
TI - Timed network games with clocks
VL - 83
ER -
TY - JOUR
AB - The current-phase relation (CPR) of a Josephson junction (JJ) determines how the supercurrent evolves with the superconducting phase difference across the junction. Knowledge of the CPR is essential in order to understand the response of a JJ to various external parameters. Despite the rising interest in ultraclean encapsulated graphene JJs, the CPR of such junctions remains unknown. Here, we use a fully gate-tunable graphene superconducting quantum intereference device (SQUID) to determine the CPR of ballistic graphene JJs. Each of the two JJs in the SQUID is made with graphene encapsulated in hexagonal boron nitride. By independently controlling the critical current of the JJs, we can operate the SQUID either in a symmetric or asymmetric configuration. The highly asymmetric SQUID allows us to phase-bias one of the JJs and thereby directly obtain its CPR. The CPR is found to be skewed, deviating significantly from a sinusoidal form. The skewness can be tuned with the gate voltage and oscillates in antiphase with Fabry-Pérot resistance oscillations of the ballistic graphene cavity. We compare our experiments with tight-binding calculations that include realistic graphene-superconductor interfaces and find a good qualitative agreement.
AU - Nanda, Gaurav
AU - Aguilera Servin, Juan L
AU - Rakyta, Péter
AU - Kormányos, Andor
AU - Kleiner, Reinhold
AU - Koelle, Dieter
AU - Watanabe, Kazuo
AU - Taniguchi, Takashi
AU - Vandersypen, Lieven
AU - Goswami, Srijit
ID - 988
IS - 6
JF - Nano Letters
SN - 15306984
TI - Current-phase relation of ballistic graphene Josephson junctions
VL - 17
ER -
TY - CONF
AB - We present a generalized optimal transport model in which the mass-preserving constraint for the L2-Wasserstein distance is relaxed by introducing a source term in the continuity equation. The source term is also incorporated in the path energy by means of its squared L2-norm in time of a functional with linear growth in space. This extension of the original transport model enables local density modulations, which is a desirable feature in applications such as image warping and blending. A key advantage of the use of a functional with linear growth in space is that it allows for singular sources and sinks, which can be supported on points or lines. On a technical level, the L2-norm in time ensures a disintegration of the source in time, which we use to obtain the well-posedness of the model and the existence of geodesic paths. The numerical discretization is based on the proximal splitting approach [18] and selected numerical test cases show the potential of the proposed approach. Furthermore, the approach is applied to the warping and blending of textures.
AU - Maas, Jan
AU - Rumpf, Martin
AU - Simon, Stefan
ED - Lauze, François
ED - Dong, Yiqiu
ED - Bjorholm Dahl, Anders
ID - 989
SN - 03029743
TI - Transport based image morphing with intensity modulation
VL - 10302
ER -
TY - JOUR
AB - Assortative mating is an important driver of speciation in populations with gene flow and is predicted to evolve under certain conditions in few-locus models. However, the evolution of assortment is less understood for mating based on quantitative traits, which are often characterized by high genetic variability and extensive linkage disequilibrium between trait loci. We explore this scenario for a two-deme model with migration, by considering a single polygenic trait subject to divergent viability selection across demes, as well as assortative mating and sexual selection within demes, and investigate how trait divergence is shaped by various evolutionary forces. Our analysis reveals the existence of sharp thresholds of assortment strength, at which divergence increases dramatically. We also study the evolution of assortment via invasion of modifiers of mate discrimination and show that the ES assortment strength has an intermediate value under a range of migration-selection parameters, even in diverged populations, due to subtle effects which depend sensitively on the extent of phenotypic variation within these populations. The evolutionary dynamics of the polygenic trait is studied using the hypergeometric and infinitesimal models. We further investigate the sensitivity of our results to the assumptions of the hypergeometric model, using individual-based simulations.
AU - Sachdeva, Himani
AU - Barton, Nicholas H
ID - 990
IS - 6
JF - Evolution; International Journal of Organic Evolution
SN - 00143820
TI - Divergence and evolution of assortative mating in a polygenic trait model of speciation with gene flow
VL - 71
ER -
TY - JOUR
AB - Synaptotagmin 7 (Syt7) was originally identified as a slow Ca2+ sensor for lysosome fusion, but its function at fast synapses is controversial. The paper by Luo and Südhof (2017) in this issue of Neuron shows that at the calyx of Held in the auditory brainstem Syt7 triggers asynchronous release during stimulus trains, resulting in reliable and temporally precise high-frequency transmission. Thus, a slow Ca2+ sensor contributes to the fast signaling properties of the calyx synapse.
AU - Chen, Chong
AU - Jonas, Peter M
ID - 991
IS - 4
JF - Neuron
SN - 08966273
TI - Synaptotagmins: That’s why so many
VL - 94
ER -
TY - THES
AB - An instance of the Constraint Satisfaction Problem (CSP) is given by a finite set of
variables, a finite domain of labels, and a set of constraints, each constraint acting on
a subset of the variables. The goal is to find an assignment of labels to its variables
that satisfies all constraints (or decide whether one exists). If we allow more general
“soft” constraints, which come with (possibly infinite) costs of particular assignments,
we obtain instances from a richer class called Valued Constraint Satisfaction Problem
(VCSP). There the goal is to find an assignment with minimum total cost.
In this thesis, we focus (assuming that P
6
=
NP) on classifying computational com-
plexity of CSPs and VCSPs under certain restricting conditions. Two results are the core
content of the work. In one of them, we consider VCSPs parametrized by a constraint
language, that is the set of “soft” constraints allowed to form the instances, and finish
the complexity classification modulo (missing pieces of) complexity classification for
analogously parametrized CSP. The other result is a generalization of Edmonds’ perfect
matching algorithm. This generalization contributes to complexity classfications in two
ways. First, it gives a new (largest known) polynomial-time solvable class of Boolean
CSPs in which every variable may appear in at most two constraints and second, it
settles full classification of Boolean CSPs with planar drawing (again parametrized by a
constraint language).
AU - Rolinek, Michal
ID - 992
TI - Complexity of constraint satisfaction
ER -
TY - JOUR
AB - In real-world applications, observations are often constrained to a small fraction of a system. Such spatial subsampling can be caused by the inaccessibility or the sheer size of the system, and cannot be overcome by longer sampling. Spatial subsampling can strongly bias inferences about a system’s aggregated properties. To overcome the bias, we derive analytically a subsampling scaling framework that is applicable to different observables, including distributions of neuronal avalanches, of number of people infected during an epidemic outbreak, and of node degrees. We demonstrate how to infer the correct distributions of the underlying full system, how to apply it to distinguish critical from subcritical systems, and how to disentangle subsampling and finite size effects. Lastly, we apply subsampling scaling to neuronal avalanche models and to recordings from developing neural networks. We show that only mature, but not young networks follow power-law scaling, indicating self-organization to criticality during development.
AU - Levina (Martius), Anna
AU - Priesemann, Viola
ID - 993
JF - Nature Communications
SN - 20411723
TI - Subsampling scaling
VL - 8
ER -
TY - JOUR
AB - The formation of vortices is usually considered to be the main mechanism of angular momentum disposal in superfluids. Recently, it was predicted that a superfluid can acquire angular momentum via an alternative, microscopic route -- namely, through interaction with rotating impurities, forming so-called `angulon quasiparticles' [Phys. Rev. Lett. 114, 203001 (2015)]. The angulon instabilities correspond to transfer of a small number of angular momentum quanta from the impurity to the superfluid, as opposed to vortex instabilities, where angular momentum is quantized in units of ℏ per atom. Furthermore, since conventional impurities (such as molecules) represent three-dimensional (3D) rotors, the angular momentum transferred is intrinsically 3D as well, as opposed to a merely planar rotation which is inherent to vortices. Herein we show that the angulon theory can explain the anomalous broadening of the spectroscopic lines observed for CH 3 and NH 3 molecules in superfluid helium nanodroplets, thereby providing a fingerprint of the emerging angulon instabilities in experiment.
AU - Cherepanov, Igor
AU - Lemeshko, Mikhail
ID - 994
IS - 3
JF - Physical Review Materials
TI - Fingerprints of angulon instabilities in the spectra of matrix-isolated molecules
VL - 1
ER -
TY - JOUR
AB - Recently it was shown that an impurity exchanging orbital angular momentum with a surrounding bath can be described in terms of the angulon quasiparticle [Phys. Rev. Lett. 118, 095301 (2017)]. The angulon consists of a quantum rotor dressed by a many-particle field of boson excitations, and can be formed out of, for example, a molecule or a nonspherical atom in superfluid helium, or out of an electron coupled to lattice phonons or a Bose condensate. Here we develop an approach to the angulon based on the path-integral formalism, which sets the ground for a systematic, perturbative treatment of the angulon problem. The resulting perturbation series can be interpreted in terms of Feynman diagrams, from which, in turn, one can derive a set of diagrammatic rules. These rules extend the machinery of the graphical theory of angular momentum - well known from theoretical atomic spectroscopy - to the case where an environment with an infinite number of degrees of freedom is present. In particular, we show that each diagram can be interpreted as a 'skeleton', which enforces angular momentum conservation, dressed by an additional many-body contribution. This connection between the angulon theory and the graphical theory of angular momentum is particularly important as it allows to systematically and substantially simplify the analytical representation of each diagram. In order to exemplify the technique, we calculate the 1- and 2-loop contributions to the angulon self-energy, the spectral function, and the quasiparticle weight. The diagrammatic theory we develop paves the way to investigate next-to-leading order quantities in a more compact way compared to the variational approaches.
AU - Bighin, Giacomo
AU - Lemeshko, Mikhail
ID - 995
IS - 8
JF - Physical Review B - Condensed Matter and Materials Physics
SN - 24699950
TI - Diagrammatic approach to orbital quantum impurities interacting with a many-particle environment
VL - 96
ER -
TY - JOUR
AB - Iodine (I 2 ) molecules embedded in He nanodroplets are aligned by a 160 ps long laser pulse. The highest degree of alignment, occurring at the peak of the pulse and quantified by ⟨cos 2 θ 2D ⟩ , is measured as a function of the laser intensity. The results are well described by ⟨cos 2 θ 2D ⟩ calculated for a gas of isolated molecules each with an effective rotational constant of 0.6 times the gas-phase value, and at a temperature of 0.4 K. Theoretical analysis using the angulon quasiparticle to describe rotating molecules in superfluid helium rationalizes why the alignment mechanism is similar to that of isolated molecules with an effective rotational constant. A major advantage of molecules in He droplets is that their 0.4 K temperature leads to stronger alignment than what can generally be achieved for gas phase molecules -- here demonstrated by a direct comparison of the droplet results to measurements on a ∼ 1 K supersonic beam of isolated molecules. This point is further illustrated for more complex system by measurements on 1,4-diiodobenzene and 1,4-dibromobenzene. For all three molecular species studied the highest values of ⟨cos 2 θ 2D ⟩ achieved in He droplets exceed 0.96.
AU - Shepperson, Benjamin
AU - Chatterley, Adam
AU - Søndergaard, Anders
AU - Christiansen, Lars
AU - Lemeshko, Mikhail
AU - Stapelfeldt, Henrik
ID - 996
IS - 1
JF - The Journal of Chemical Physics
SN - 00219606
TI - Strongly aligned molecules inside helium droplets in the near-adiabatic regime
VL - 147
ER -
TY - JOUR
AB - Recently it was shown that molecules rotating in superfluid helium can be described in terms of the angulon quasiparticles (Phys. Rev. Lett. 118, 095301 (2017)). Here we demonstrate that in the experimentally realized regime the angulon can be seen as a point charge on a 2-sphere interacting with a gauge field of a non-abelian magnetic monopole. Unlike in several other settings, the gauge fields of the angulon problem emerge in the real coordinate space, as opposed to the momentum space or some effective parameter space. Furthermore, we find a topological transition associated with making the monopole abelian, which takes place in the vicinity of the previously reported angulon instabilities. These results pave the way for studying topological phenomena in experiments on molecules trapped in superfluid helium nanodroplets, as well as on other realizations of orbital impurity problems.
AU - Yakaboylu, Enderalp
AU - Deuchert, Andreas
AU - Lemeshko, Mikhail
ID - 997
IS - 23
JF - APS Physics, Physical Review Letters
SN - 00319007
TI - Emergence of non-abelian magnetic monopoles in a quantum impurity problem
VL - 119
ER -
TY - CONF
AB - A major open problem on the road to artificial intelligence is the development of incrementally learning systems that learn about more and more concepts over time from a stream of data. In this work, we introduce a new training strategy, iCaRL, that allows learning in such a class-incremental way: only the training data for a small number of classes has to be present at the same time and new classes can be added progressively. iCaRL learns strong classifiers and a data representation simultaneously. This distinguishes it from earlier works that were fundamentally limited to fixed data representations and therefore incompatible with deep learning architectures. We show by experiments on CIFAR-100 and ImageNet ILSVRC 2012 data that iCaRL can learn many classes incrementally over a long period of time where other strategies quickly fail.
AU - Rebuffi, Sylvestre Alvise
AU - Kolesnikov, Alexander
AU - Sperl, Georg
AU - Lampert, Christoph
ID - 998
SN - 978-153860457-1
TI - iCaRL: Incremental classifier and representation learning
VL - 2017
ER -
TY - CHAP
AB - We show that very weak topological assumptions are enough to ensure the existence of a Helly-type theorem. More precisely, we show that for any non-negative integers b and d there exists an integer h(b, d) such that the following holds. If F is a finite family of subsets of Rd such that βi(∩G)≤b for any G⊊F and every 0 ≤ i ≤ [d/2]-1 then F has Helly number at most h(b, d). Here βi denotes the reduced Z2-Betti numbers (with singular homology). These topological conditions are sharp: not controlling any of these [d/2] first Betti numbers allow for families with unbounded Helly number. Our proofs combine homological non-embeddability results with a Ramsey-based approach to build, given an arbitrary simplicial complex K, some well-behaved chain map C*(K)→C*(Rd).
AU - Goaoc, Xavier
AU - Paták, Pavel
AU - Patakova, Zuzana
AU - Tancer, Martin
AU - Wagner, Uli
ED - Loebl, Martin
ED - Nešetřil, Jaroslav
ED - Thomas, Robin
ID - 424
SN - 978-331944479-6
T2 - A Journey through Discrete Mathematics: A Tribute to Jiri Matousek
TI - Bounding helly numbers via betti numbers
ER -
TY - CONF
AB - Parallel implementations of stochastic gradient descent (SGD) have received significant research attention, thanks to its excellent scalability properties. A fundamental barrier when parallelizing SGD is the high bandwidth cost of communicating gradient updates between nodes; consequently, several lossy compresion heuristics have been proposed, by which nodes only communicate quantized gradients. Although effective in practice, these heuristics do not always converge. In this paper, we propose Quantized SGD (QSGD), a family of compression schemes with convergence guarantees and good practical performance. QSGD allows the user to smoothly trade off communication bandwidth and convergence time: nodes can adjust the number of bits sent per iteration, at the cost of possibly higher variance. We show that this trade-off is inherent, in the sense that improving it past some threshold would violate information-theoretic lower bounds. QSGD guarantees convergence for convex and non-convex objectives, under asynchrony, and can be extended to stochastic variance-reduced techniques. When applied to training deep neural networks for image classification and automated speech recognition, QSGD leads to significant reductions in end-to-end training time. For instance, on 16GPUs, we can train the ResNet-152 network to full accuracy on ImageNet 1.8 × faster than the full-precision variant.
AU - Alistarh, Dan-Adrian
AU - Grubic, Demjan
AU - Li, Jerry
AU - Tomioka, Ryota
AU - Vojnović, Milan
ID - 431
SN - 10495258
TI - QSGD: Communication-efficient SGD via gradient quantization and encoding
VL - 2017
ER -