TY - CHAP
AU - Wenzl, Bernhard
ED - Parker, Joshua
ED - Poole, Ralph
ID - 1075
SN - 978-3643908124
T2 - Austria and America: 20th-Century Cross-Cultural Encounters
TI - An American in Allied-occupied Austria: John Dos Passos Reports on "The Vienna Frontier"
VL - 15
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 ϕX174 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 - JOUR
AB - The generation, migration, and differentiation of neurons requires the functional integrity of the microtubule cytoskeleton. Mutations in the tubulin gene family are known to cause various neurological diseases including lissencephaly, ocular motor disorders, polymicrogyria and amyotrophic lateral sclerosis. We have previously reported that mutations in TUBB5 cause microcephaly that is accompanied by severe intellectual impairment and motor delay. Here we present the characterization of a Tubb5 mouse model that allows for the conditional expression of the pathogenic E401K mutation. Homozygous knockin animals exhibit a severe reduction in brain size and in body weight. These animals do not show any significant impairment in general activity, anxiety, or in the acoustic startle response, however, present with notable defects in motor coordination. When assessed on the static rod apparatus mice took longer to orient and often lost their balance completely. Interestingly, mutant animals also showed defects in prepulse inhibition, a phenotype associated with sensorimotor gating and considered an endophenotype for schizophrenia. This study provides insight into the behavioral consequences of tubulin gene mutations.
AU - Breuss, Martin
AU - Hansen, Andi H
AU - Landler, Lukas
AU - Keays, David
ID - 1107
JF - Behavioural Brain Research
SN - 01664328
TI - Brain specific knockin of the pathogenic Tubb5 E401K allele causes defects in motor coordination and prepulse inhibition
VL - 323
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 - THES
AB - Plant hormone auxin and its transport between cells belong to the most important
mechanisms controlling plant development. Auxin itself could change localization of PINs and
thereby control direction of its own flow. We performed an expression profiling experiment
in Arabidopsis roots to identify potential regulators of PIN polarity which are transcriptionally
regulated by auxin signalling. We identified several novel regulators and performed a detailed
characterization of the transcription factor WRKY23 (At2g47260) and its role in auxin
feedback on PIN polarity. Gain-of-function and dominant-negative mutants revealed that
WRKY23 plays a crucial role in mediating the auxin effect on PIN polarity. In concordance,
typical polar auxin transport processes such as gravitropism and leaf vascular pattern
formation were disturbed by interfering with WRKY23 function.
In order to identify direct targets of WRKY23, we performed consequential expression
profiling experiments using a WRKY23 inducible gain-of-function line and dominant-negative
WRKY23 line that is defunct in PIN re-arrangement. Among several genes mostly related to
the groups of cell wall and defense process regulators, we identified LYSINE-HISTIDINE
TRANSPORTER 1 (LHT1; At5g40780), a small amino acid permease gene from the amino
acid/auxin permease family (AAAP), we present its detailed characterisation in auxin feedback
on PIN repolarization, identified its transcriptional regulation, we propose a potential
mechanism of its action. Moreover, we identified also a member of receptor-like protein
kinase LRR-RLK (LEUCINE-RICH REPEAT TRANSMEMBRANE PROTEIN KINASE PROTEIN 1;
LRRK1; At1g05700), which also affects auxin-dependent PIN re-arrangement. We described
its transcriptional behaviour, subcellular localization. Based on global expression data, we
tried to identify ligand responsible for mechanism of signalling and suggest signalling partner
and interactors. Additionally, we described role of novel phytohormone group, strigolactone,
in auxin-dependent PIN re-arrangement, that could be a fundament for future studies in this
field.
Our results provide first insights into an auxin transcriptional network targeting PIN
localization and thus regulating plant development. We highlighted WRKY23 transcriptional
network and characterised its mediatory role in plant development. We identified direct
effectors of this network, LHT1 and LRRK1, and describe their roles in PIN re-arrangement and
PIN-dependent auxin transport processes.
AU - Prat, Tomas
ID - 1127
TI - Identification of novel regulators of PIN polarity and development of novel auxin sensor
ER -
TY - JOUR
AB - 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 - 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 show that a twisted variant of Linnik’s conjecture on sums of Kloosterman sums leads to an optimal covering exponent for S3.
AU - Browning, Timothy D
AU - Kumaraswamy, Vinay
AU - Steiner, Rapael
ID - 169
JF - International Mathematics Research Notices
TI - Twisted Linnik implies optimal covering exponent for S3
ER -
TY - JOUR
AB - We study strong approximation for some algebraic varieties over ℚ which are defined using norm forms. This allows us to confirm a special case of a conjecture due to Harpaz and Wittenberg.
AU - Browning, Timothy D
AU - Schindler, Damaris
ID - 172
JF - International Mathematics Research Notices
TI - Strong approximation and a conjecture of Harpaz and Wittenberg
ER -
TY - CONF
AB - Several cryptographic schemes and applications are based on functions that are both reasonably efficient to compute and moderately hard to invert, including client puzzles for Denial-of-Service protection, password protection via salted hashes, or recent proof-of-work blockchain systems. Despite their wide use, a definition of this concept has not yet been distilled and formalized explicitly. Instead, either the applications are proven directly based on the assumptions underlying the function, or some property of the function is proven, but the security of the application is argued only informally. The goal of this work is to provide a (universal) definition that decouples the efforts of designing new moderately hard functions and of building protocols based on them, serving as an interface between the two. On a technical level, beyond the mentioned definitions, we instantiate the model for four different notions of hardness. We extend the work of Alwen and Serbinenko (STOC 2015) by providing a general tool for proving security for the first notion of memory-hard functions that allows for provably secure applications. The tool allows us to recover all of the graph-theoretic techniques developed for proving security under the older, non-composable, notion of security used by Alwen and Serbinenko. As an application of our definition of moderately hard functions, we prove the security of two different schemes for proofs of effort (PoE). We also formalize and instantiate the concept of a non-interactive proof of effort (niPoE), in which the proof is not bound to a particular communication context but rather any bit-string chosen by the prover.
AU - Alwen, Joel F
AU - Tackmann, Björn
ED - Kalai, Yael
ED - Reyzin, Leonid
ID - 609
SN - 978-331970499-9
TI - Moderately hard functions: Definition, instantiations, and applications
VL - 10677
ER -
TY - JOUR
AB - The fact that the complete graph K5 does not embed in the plane has been generalized in two independent directions. On the one hand, the solution of the classical Heawood problem for graphs on surfaces established that the complete graph Kn embeds in a closed surface M (other than the Klein bottle) if and only if (n−3)(n−4) ≤ 6b1(M), where b1(M) is the first Z2-Betti number of M. On the other hand, van Kampen and Flores proved that the k-skeleton of the n-dimensional simplex (the higher-dimensional analogue of Kn+1) embeds in R2k if and only if n ≤ 2k + 1. Two decades ago, Kühnel conjectured that the k-skeleton of the n-simplex embeds in a compact, (k − 1)-connected 2k-manifold with kth Z2-Betti number bk only if the following generalized Heawood inequality holds: (k+1 n−k−1) ≤ (k+1 2k+1)bk. This is a common generalization of the case of graphs on surfaces as well as the van Kampen–Flores theorem. In the spirit of Kühnel’s conjecture, we prove that if the k-skeleton of the n-simplex embeds in a compact 2k-manifold with kth Z2-Betti number bk, then n ≤ 2bk(k 2k+2)+2k+4. This bound is weaker than the generalized Heawood inequality, but does not require the assumption that M is (k−1)-connected. Our results generalize to maps without q-covered points, in the spirit of Tverberg’s theorem, for q a prime power. Our proof uses a result of Volovikov about maps that satisfy a certain homological triviality condition.
AU - Goaoc, Xavier
AU - Mabillard, Isaac
AU - Paták, Pavel
AU - Patakova, Zuzana
AU - Tancer, Martin
AU - Wagner, Uli
ID - 610
IS - 2
JF - Israel Journal of Mathematics
TI - On generalized Heawood inequalities for manifolds: A van Kampen–Flores type nonembeddability result
VL - 222
ER -
TY - JOUR
AB - Small RNAs (sRNAs) regulate genes in plants and animals. Here, we show that population-wide differences in color patterns in snapdragon flowers are caused by an inverted duplication that generates sRNAs. The complexity and size of the transcripts indicate that the duplication represents an intermediate on the pathway to microRNA evolution. The sRNAs repress a pigment biosynthesis gene, creating a yellow highlight at the site of pollinator entry. The inverted duplication exhibits steep clines in allele frequency in a natural hybrid zone, showing that the allele is under selection. Thus, regulatory interactions of evolutionarily recent sRNAs can be acted upon by selection and contribute to the evolution of phenotypic diversity.
AU - Bradley, Desmond
AU - Xu, Ping
AU - Mohorianu, Irina
AU - Whibley, Annabel
AU - Field, David
AU - Tavares, Hugo
AU - Couchman, Matthew
AU - Copsey, Lucy
AU - Carpenter, Rosemary
AU - Li, Miaomiao
AU - Li, Qun
AU - Xue, Yongbiao
AU - Dalmay, Tamas
AU - Coen, Enrico
ID - 611
IS - 6365
JF - Science
SN - 00368075
TI - Evolution of flower color pattern through selection on regulatory small RNAs
VL - 358
ER -
TY - JOUR
AU - Oda, Shigekazu
AU - Toyoshima, Yu
AU - de Bono, Mario
ID - 6113
IS - 23
JF - Proceedings of the National Academy of Sciences
SN - 0027-8424
TI - Modulation of sensory information processing by a neuroglobin in Caenorhabditis elegans
VL - 114
ER -
TY - JOUR
AB - Animals adjust their behavioral priorities according to momentary needs and prior experience. We show that Caenorhabditis elegans changes how it processes sensory information according to the oxygen environment it experienced recently. C. elegans acclimated to 7% O2 are aroused by CO2 and repelled by pheromones that attract animals acclimated to 21% O2. This behavioral plasticity arises from prolonged activity differences in a circuit that continuously signals O2 levels. A sustained change in the activity of O2-sensing neurons reprograms the properties of their postsynaptic partners, the RMG hub interneurons. RMG is gap-junctionally coupled to the ASK and ADL pheromone sensors that respectively drive pheromone attraction and repulsion. Prior O2 experience has opposite effects on the pheromone responsiveness of these neurons. These circuit changes provide a physiological correlate of altered pheromone valence. Our results suggest C. elegans stores a memory of recent O2 experience in the RMG circuit and illustrate how a circuit is flexibly sculpted to guide behavioral decisions in a context-dependent manner.
AU - Fenk, Lorenz A.
AU - de Bono, Mario
ID - 6115
IS - 16
JF - Proceedings of the National Academy of Sciences
SN - 0027-8424
TI - Memory of recent oxygen experience switches pheromone valence inCaenorhabditis elegans
VL - 114
ER -
TY - JOUR
AB - Interleukin-17 (IL-17) is a major pro-inflammatory cytokine: it mediates responses to pathogens or tissue damage, and drives autoimmune diseases. Little is known about its role in the nervous system. Here we show that IL-17 has neuromodulator-like properties in Caenorhabditis elegans. IL-17 can act directly on neurons to alter their response properties and contribution to behaviour. Using unbiased genetic screens, we delineate an IL-17 signalling pathway and show that it acts in the RMG hub interneurons. Disrupting IL-17 signalling reduces RMG responsiveness to input from oxygen sensors, and renders sustained escape from 21% oxygen transient and contingent on additional stimuli. Over-activating IL-17 receptors abnormally heightens responses to 21% oxygen in RMG neurons and whole animals. IL-17 deficiency can be bypassed by optogenetic stimulation of RMG. Inducing IL-17 expression in adults can rescue mutant defects within 6 h. These findings reveal a non-immunological role of IL-17 modulating circuit function and behaviour.
AU - Chen, Changchun
AU - Itakura, Eisuke
AU - Nelson, Geoffrey M.
AU - Sheng, Ming
AU - Laurent, Patrick
AU - Fenk, Lorenz A.
AU - Butcher, Rebecca A.
AU - Hegde, Ramanujan S.
AU - de Bono, Mario
ID - 6117
IS - 7639
JF - Nature
SN - 0028-0836
TI - IL-17 is a neuromodulator of Caenorhabditis elegans sensory responses
VL - 542
ER -
TY - JOUR
AB - Bacteria in groups vary individually, and interact with other bacteria and the environment to produce population-level patterns of gene expression. Investigating such behavior in detail requires measuring and controlling populations at the single-cell level alongside precisely specified interactions and environmental characteristics. Here we present an automated, programmable platform that combines image-based gene expression and growth measurements with on-line optogenetic expression control for hundreds of individual Escherichia coli cells over days, in a dynamically adjustable environment. This integrated platform broadly enables experiments that bridge individual and population behaviors. We demonstrate: (i) population structuring by independent closed-loop control of gene expression in many individual cells, (ii) cell-cell variation control during antibiotic perturbation, (iii) hybrid bio-digital circuits in single cells, and freely specifiable digital communication between individual bacteria. These examples showcase the potential for real-time integration of theoretical models with measurement and control of many individual cells to investigate and engineer microbial population behavior.
AU - Chait, Remy P
AU - Ruess, Jakob
AU - Bergmiller, Tobias
AU - Tkacik, Gasper
AU - Guet, Calin C
ID - 613
IS - 1
JF - Nature Communications
SN - 20411723
TI - Shaping bacterial population behavior through computer interfaced control of individual cells
VL - 8
ER -
TY - JOUR
AB - Moths and butterflies (Lepidoptera) usually have a pair of differentiated WZ sex chromosomes. However, in most lineages outside of the division Ditrysia, as well as in the sister order Trichoptera, females lack a W chromosome. The W is therefore thought to have been acquired secondarily. Here we compare the genomes of three Lepidoptera species (one Dytrisia and two non-Dytrisia) to test three models accounting for the origin of the W: (1) a Z-autosome fusion; (2) a sex chromosome turnover; and (3) a non-canonical mechanism (e.g., through the recruitment of a B chromosome). We show that the gene content of the Z is highly conserved across Lepidoptera (rejecting a sex chromosome turnover) and that very few genes moved onto the Z in the common ancestor of the Ditrysia (arguing against a Z-autosome fusion). Our comparative genomics analysis therefore supports the secondary acquisition of the Lepidoptera W by a non-canonical mechanism, and it confirms the extreme stability of well-differentiated sex chromosomes.
AU - Fraisse, Christelle
AU - Picard, Marion A
AU - Vicoso, Beatriz
ID - 614
IS - 1
JF - Nature Communications
SN - 20411723
TI - The deep conservation of the Lepidoptera Z chromosome suggests a non canonical origin of the W
VL - 8
ER -
TY - JOUR
AB - We show that the Dyson Brownian Motion exhibits local universality after a very short time assuming that local rigidity and level repulsion of the eigenvalues hold. These conditions are verified, hence bulk spectral universality is proven, for a large class of Wigner-like matrices, including deformed Wigner ensembles and ensembles with non-stochastic variance matrices whose limiting densities differ from Wigner's semicircle law.
AU - Erdös, László
AU - Schnelli, Kevin
ID - 615
IS - 4
JF - Annales de l'institut Henri Poincare (B) Probability and Statistics
SN - 02460203
TI - Universality for random matrix flows with time dependent density
VL - 53
ER -
TY - JOUR
AB - Background: Increasing temperatures are predicted to strongly impact host-parasite interactions, but empirical tests are rare. Host species that are naturally exposed to a broad temperature spectrum offer the possibility to investigate the effects of elevated temperatures on hosts and parasites. Using three-spined sticklebacks, Gasterosteus aculeatus L., and tapeworms, Schistocephalus solidus (Müller, 1776), originating from a cold and a warm water site of a volcanic lake, we subjected sympatric and allopatric host-parasite combinations to cold and warm conditions in a fully crossed design. We predicted that warm temperatures would promote the development of the parasites, while the hosts might benefit from cooler temperatures. We further expected adaptations to the local temperature and mutual adaptations of local host-parasite pairs. Results: Overall, S. solidus parasites grew faster at warm temperatures and stickleback hosts at cold temperatures. On a finer scale, we observed that parasites were able to exploit their hosts more efficiently at the parasite’s temperature of origin. In contrast, host tolerance towards parasite infection was higher when sticklebacks were infected with parasites at the parasite’s ‘foreign’ temperature. Cold-origin sticklebacks tended to grow faster and parasite infection induced a stronger immune response. Conclusions: Our results suggest that increasing environmental temperatures promote the parasite rather than the host and that host tolerance is dependent on the interaction between parasite infection and temperature. Sticklebacks might use tolerance mechanisms towards parasite infection in combination with their high plasticity towards temperature changes to cope with increasing parasite infection pressures and rising temperatures.
AU - Franke, Frederik
AU - Armitage, Sophie
AU - Kutzer, Megan
AU - Kurtz, Joachim
AU - Scharsack, Jörn
ID - 618
IS - 252
JF - Parasites & Vectors
SN - 17563305
TI - Environmental temperature variation influences fitness trade-offs in a fish-tapeworm association
VL - 10
ER -
TY - JOUR
AB - PMAC is a simple and parallel block-cipher mode of operation, which was introduced by Black and Rogaway at Eurocrypt 2002. If instantiated with a (pseudo)random permutation over n-bit strings, PMAC constitutes a provably secure variable input-length (pseudo)random function. For adversaries making q queries, each of length at most l (in n-bit blocks), and of total length σ ≤ ql, the original paper proves an upper bound on the distinguishing advantage of Ο(σ2/2n), while the currently best bound is Ο (qσ/2n).In this work we show that this bound is tight by giving an attack with advantage Ω (q2l/2n). In the PMAC construction one initially XORs a mask to every message block, where the mask for the ith block is computed as τi := γi·L, where L is a (secret) random value, and γi is the i-th codeword of the Gray code. Our attack applies more generally to any sequence of γi’s which contains a large coset of a subgroup of GF(2n). We then investigate if the security of PMAC can be further improved by using τi’s that are k-wise independent, for k > 1 (the original distribution is only 1-wise independent). We observe that the security of PMAC will not increase in general, even if the masks are chosen from a 2-wise independent distribution, and then prove that the security increases to O(q<2/2n), if the τi are 4-wise independent. Due to simple extension attacks, this is the best bound one can hope for, using any distribution on the masks. Whether 3-wise independence is already sufficient to get this level of security is left as an open problem.
AU - Gazi, Peter
AU - Pietrzak, Krzysztof Z
AU - Rybar, Michal
ID - 6196
IS - 2
JF - IACR Transactions on Symmetric Cryptology
TI - The exact security of PMAC
VL - 2016
ER -
TY - JOUR
AB - The mammalian cerebral cortex is responsible for higher cognitive functions such as perception, consciousness, and acquiring and processing information. The neocortex is organized into six distinct laminae, each composed of a rich diversity of cell types which assemble into highly complex cortical circuits. Radial glia progenitors (RGPs) are responsible for producing all neocortical neurons and certain glia lineages. Here, we discuss recent discoveries emerging from clonal lineage analysis at the single RGP cell level that provide us with an inaugural quantitative framework of RGP lineage progression. We further discuss the importance of the relative contribution of intrinsic gene functions and non-cell-autonomous or community effects in regulating RGP proliferation behavior and lineage progression.
AU - Beattie, Robert J
AU - Hippenmeyer, Simon
ID - 621
IS - 24
JF - FEBS letters
SN - 00145793
TI - Mechanisms of radial glia progenitor cell lineage progression
VL - 591
ER -
TY - CHAP
AB - Genetic factors might be largely responsible for the development of autism spectrum disorder (ASD) that alone or in combination with specific environmental risk factors trigger the pathology. Multiple mutations identified in ASD patients that impair synaptic function in the central nervous system are well studied in animal models. How these mutations might interact with other risk factors is not fully understood though. Additionally, how systems outside of the brain are altered in the context of ASD is an emerging area of research. Extracerebral influences on the physiology could begin in utero and contribute to changes in the brain and in the development of other body systems and further lead to epigenetic changes. Therefore, multiple recent studies have aimed at elucidating the role of gene-environment interactions in ASD. Here we provide an overview on the extracerebral systems that might play an important associative role in ASD and review evidence regarding the potential roles of inflammation, trace metals, metabolism, genetic susceptibility, enteric nervous system function and the microbiota of the gastrointestinal (GI) tract on the development of endophenotypes in animal models of ASD. By influencing environmental conditions, it might be possible to reduce or limit the severity of ASD pathology.
AU - Hill Yardin, Elisa
AU - Mckeown, Sonja
AU - Novarino, Gaia
AU - Grabrucker, Andreas
ED - Schmeisser, Michael
ED - Boekers, Tobias
ID - 623
SN - 03015556
T2 - Translational Anatomy and Cell Biology of Autism Spectrum Disorder
TI - Extracerebral dysfunction in animal models of autism spectrum disorder
VL - 224
ER -
TY - JOUR
AB - Bacteria adapt to adverse environmental conditions by altering gene expression patterns. Recently, a novel stress adaptation mechanism has been described that allows Escherichia coli to alter gene expression at the post-transcriptional level. The key player in this regulatory pathway is the endoribonuclease MazF, the toxin component of the toxin-antitoxin module mazEF that is triggered by various stressful conditions. In general, MazF degrades the majority of transcripts by cleaving at ACA sites, which results in the retardation of bacterial growth. Furthermore, MazF can process a small subset of mRNAs and render them leaderless by removing their ribosome binding site. MazF concomitantly modifies ribosomes, making them selective for the translation of leaderless mRNAs. In this study, we employed fluorescent reporter-systems to investigate mazEF expression during stressful conditions, and to infer consequences of the mRNA processing mediated by MazF on gene expression at the single-cell level. Our results suggest that mazEF transcription is maintained at low levels in single cells encountering adverse conditions, such as antibiotic stress or amino acid starvation. Moreover, using the grcA mRNA as a model for MazF-mediated mRNA processing, we found that MazF activation promotes heterogeneity in the grcA reporter expression, resulting in a subpopulation of cells with increased levels of GrcA reporter protein.
AU - Nikolic, Nela
AU - Didara, Zrinka
AU - Moll, Isabella
ID - 624
IS - 9
JF - PeerJ
SN - 21678359
TI - MazF activation promotes translational heterogeneity of the grcA mRNA in Escherichia coli populations
VL - 2017
ER -
TY - JOUR
AB - Our focus here is on the infinitesimal model. In this model, one or several quantitative traits are described as the sum of a genetic and a non-genetic component, the first being distributed within families as a normal random variable centred at the average of the parental genetic components, and with a variance independent of the parental traits. Thus, the variance that segregates within families is not perturbed by selection, and can be predicted from the variance components. This does not necessarily imply that the trait distribution across the whole population should be Gaussian, and indeed selection or population structure may have a substantial effect on the overall trait distribution. One of our main aims is to identify some general conditions on the allelic effects for the infinitesimal model to be accurate. We first review the long history of the infinitesimal model in quantitative genetics. Then we formulate the model at the phenotypic level in terms of individual trait values and relationships between individuals, but including different evolutionary processes: genetic drift, recombination, selection, mutation, population structure, …. We give a range of examples of its application to evolutionary questions related to stabilising selection, assortative mating, effective population size and response to selection, habitat preference and speciation. We provide a mathematical justification of the model as the limit as the number M of underlying loci tends to infinity of a model with Mendelian inheritance, mutation and environmental noise, when the genetic component of the trait is purely additive. We also show how the model generalises to include epistatic effects. We prove in particular that, within each family, the genetic components of the individual trait values in the current generation are indeed normally distributed with a variance independent of ancestral traits, up to an error of order 1∕M. Simulations suggest that in some cases the convergence may be as fast as 1∕M.
AU - Barton, Nicholas H
AU - Etheridge, Alison
AU - Véber, Amandine
ID - 626
JF - Theoretical Population Biology
SN - 00405809
TI - The infinitesimal model: Definition derivation and implications
VL - 118
ER -
TY - JOUR
AB - Beige adipocytes are a new type of recruitable brownish adipocytes, with highly mitochondrial membrane uncoupling protein 1 expression and thermogenesis. Beige adipocytes were found among white adipocytes, especially in subcutaneous white adipose tissue (sWAT). Therefore, beige adipocytes may be involved in the regulation of energy metabolism and fat deposition. Transient receptor potential melastatin 8 (TRPM8), a Ca2+-permeable non-selective cation channel, plays vital roles in the regulation of various cellular functions. It has been reported that TRPM8 activation enhanced the thermogenic function of brown adiposytes. However, the involvement of TRPM8 in the thermogenic function of WAT remains unexplored. Our data revealed that TRPM8 was expressed in mouse white adipocytes at mRNA, protein and functional levels. The mRNA expression of Trpm8 was significantly increased in the differentiated white adipocytes than pre-adipocytes. Moreover, activation of TRPM8 by menthol enhanced the expression of thermogenic genes in cultured white aidpocytes. And menthol-induced increases of the thermogenic genes in white adipocytes was inhibited by either KT5720 (a protein kinase A inhibitor) or BAPTA-AM. In addition, high fat diet (HFD)-induced obesity in mice was significantly recovered by co-treatment with menthol. Dietary menthol enhanced WAT "browning" and improved glucose metabolism in HFD-induced obesity mice as well. Therefore, we concluded that TRPM8 might be involved in WAT "browning" by increasing the expression levels of genes related to thermogenesis and energy metabolism. And dietary menthol could be a novel approach for combating human obesity and related metabolic diseases.
AU - Jiang, Changyu
AU - Zhai, Ming-Zhu
AU - Yan, Dong
AU - Li, Da
AU - Li, Chen
AU - Zhang, Yonghong
AU - Xiao, Lizu
AU - Xiong, Donglin
AU - Deng, Qiwen
AU - Sun, Wuping
ID - 627
IS - 43
JF - Oncotarget
SN - 19492553
TI - Dietary menthol-induced TRPM8 activation enhances WAT “browning” and ameliorates diet-induced obesity
VL - 8
ER -
TY - CONF
AB - We consider the problem of developing automated techniques for solving recurrence relations to aid the expected-runtime analysis of programs. The motivation is that several classical textbook algorithms have quite efficient expected-runtime complexity, whereas the corresponding worst-case bounds are either inefficient (e.g., Quick-Sort), or completely ineffective (e.g., Coupon-Collector). Since the main focus of expected-runtime analysis is to obtain efficient bounds, we consider bounds that are either logarithmic, linear or almost-linear (O(log n), O(n), O(n · log n), respectively, where n represents the input size). Our main contribution is an efficient (simple linear-time algorithm) sound approach for deriving such expected-runtime bounds for the analysis of recurrence relations induced by randomized algorithms. The experimental results show that our approach can efficiently derive asymptotically optimal expected-runtime bounds for recurrences of classical randomized algorithms, including Randomized-Search, Quick-Sort, Quick-Select, Coupon-Collector, where the worst-case bounds are either inefficient (such as linear as compared to logarithmic expected-runtime complexity, or quadratic as compared to linear or almost-linear expected-runtime complexity), or ineffective.
AU - Chatterjee, Krishnendu
AU - Fu, Hongfei
AU - Murhekar, Aniket
ED - Majumdar, Rupak
ED - Kunčak, Viktor
ID - 628
SN - 978-331963386-2
TI - Automated recurrence analysis for almost linear expected runtime bounds
VL - 10426
ER -
TY - THES
AB - The main objects considered in the present work are simplicial and CW-complexes with vertices forming a random point cloud. In particular, we consider a Poisson point process in R^n and study Delaunay and Voronoi complexes of the first and higher orders and weighted Delaunay complexes obtained as sections of Delaunay complexes, as well as the Čech complex. Further, we examine theDelaunay complex of a Poisson point process on the sphere S^n, as well as of a uniform point cloud, which is equivalent to the convex hull, providing a connection to the theory of random polytopes. Each of the complexes in question can be endowed with a radius function, which maps its cells to the radii of appropriately chosen circumspheres, called the radius of the cell. Applying and developing discrete Morse theory for these functions, joining it together with probabilistic and sometimes analytic machinery, and developing several integral geometric tools, we aim at getting the distributions of circumradii of typical cells. For all considered complexes, we are able to generalize and obtain up to constants the distribution of radii of typical intervals of all types. In low dimensions the constants can be computed explicitly, thus providing the explicit expressions for the expected numbers of cells. In particular, it allows to find the expected density of simplices of every dimension for a Poisson point process in R^4, whereas the result for R^3 was known already in 1970's.
AU - Nikitenko, Anton
ID - 6287
TI - Discrete Morse theory for random complexes
ER -
TY - CHAP
AB - Even simple cells like bacteria have precisely regulated cellular anatomies, which allow them to grow, divide and to respond to internal or external cues with high fidelity. How spatial and temporal intracellular organization in prokaryotic cells is achieved and maintained on the basis of locally interacting proteins still remains largely a mystery. Bulk biochemical assays with purified components and in vivo experiments help us to approach key cellular processes from two opposite ends, in terms of minimal and maximal complexity. However, to understand how cellular phenomena emerge, that are more than the sum of their parts, we have to assemble cellular subsystems step by step from the bottom up. Here, we review recent in vitro reconstitution experiments with proteins of the bacterial cell division machinery and illustrate how they help to shed light on fundamental cellular mechanisms that constitute spatiotemporal order and regulate cell division.
AU - Loose, Martin
AU - Zieske, Katja
AU - Schwille, Petra
ID - 629
T2 - Prokaryotic Cytoskeletons
TI - Reconstitution of protein dynamics involved in bacterial cell division
VL - 84
ER -
TY - THES
AB - Bacteria and their pathogens – phages – are the most abundant living entities on Earth. Throughout their coevolution, bacteria have evolved multiple immune systems to overcome the ubiquitous threat from the phages. Although the molecu- lar details of these immune systems’ functions are relatively well understood, their epidemiological consequences for the phage-bacterial communities have been largely neglected. In this thesis we employed both experimental and theoretical methods to explore whether herd and social immunity may arise in bacterial popu- lations. Using our experimental system consisting of Escherichia coli strains with a CRISPR based immunity to the T7 phage we show that herd immunity arises in phage-bacterial communities and that it is accentuated when the populations are spatially structured. By fitting a mathematical model, we inferred expressions for the herd immunity threshold and the velocity of spread of a phage epidemic in partially resistant bacterial populations, which both depend on the bacterial growth rate, phage burst size and phage latent period. We also investigated the poten- tial for social immunity in Streptococcus thermophilus and its phage 2972 using a bioinformatic analysis of potentially coding short open reading frames with a signalling signature, encoded within the CRISPR associated genes. Subsequently, we tested one identified potentially signalling peptide and found that its addition to a phage-challenged culture increases probability of survival of bacteria two fold, although the results were only marginally significant. Together, these results demonstrate that the ubiquitous arms races between bacteria and phages have further consequences at the level of the population.
AU - Payne, Pavel
ID - 6291
TI - Bacterial herd and social immunity to phages
ER -
TY - CONF
AB - Background: Standards have become available to share semantically encoded vital parameters from medical devices, as required for example by personal healthcare records. Standardised sharing of biosignal data largely remains open. Objectives: The goal of this work is to explore available biosignal file format and data exchange standards and profiles, and to conceptualise end-To-end solutions. Methods: The authors reviewed and discussed available biosignal file format standards with other members of international standards development organisations (SDOs). Results: A raw concept for standards based acquisition, storage, archiving and sharing of biosignals was developed. The GDF format may serve for storing biosignals. Signals can then be shared using FHIR resources and may be stored on FHIR servers or in DICOM archives, with DICOM waveforms as one possible format. Conclusion: Currently a group of international SDOs (e.g. HL7, IHE, DICOM, IEEE) is engaged in intensive discussions. This discussion extends existing work that already was adopted by large implementer communities. The concept presented here only reports the current status of the discussion in Austria. The discussion will continue internationally, with results to be expected over the coming years.
AU - Sauermann, Stefan
AU - David, Veronika
AU - Schlögl, Alois
AU - Egelkraut, Reinhard
AU - Frohner, Matthias
AU - Pohn, Birgit
AU - Urbauer, Philipp
AU - Mense, Alexander
ID - 630
SN - 978-161499758-0
TI - Biosignals standards and FHIR: The way to go
VL - 236
ER -
TY - CONF
AB - Template polyhedra generalize intervals and octagons to polyhedra whose facets are orthogonal to a given set of arbitrary directions. They have been employed in the abstract interpretation of programs and, with particular success, in the reachability analysis of hybrid automata. While previously, the choice of directions has been left to the user or a heuristic, we present a method for the automatic discovery of directions that generalize and eliminate spurious counterexamples. We show that for the class of convex hybrid automata, i.e., hybrid automata with (possibly nonlinear) convex constraints on derivatives, such directions always exist and can be found using convex optimization. We embed our method inside a CEGAR loop, thus enabling the time-unbounded reachability analysis of an important and richer class of hybrid automata than was previously possible. We evaluate our method on several benchmarks, demonstrating also its superior efficiency for the special case of linear hybrid automata.
AU - Bogomolov, Sergiy
AU - Frehse, Goran
AU - Giacobbe, Mirco
AU - Henzinger, Thomas A
ID - 631
SN - 978-366254576-8
TI - Counterexample guided refinement of template polyhedra
VL - 10205
ER -
TY - JOUR
AB - We consider a 2D quantum system of N bosons in a trapping potential |x|s, interacting via a pair potential of the form N2β−1 w(Nβ x). We show that for all 0 < β < (s + 1)/(s + 2), the leading order behavior of ground states of the many-body system is described in the large N limit by the corresponding cubic nonlinear Schrödinger energy functional. Our result covers the focusing case (w < 0) where even the stability of the many-body system is not obvious. This answers an open question mentioned by X. Chen and J. Holmer for harmonic traps (s = 2). Together with the BBGKY hierarchy approach used by these authors, our result implies the convergence of the many-body quantum dynamics to the focusing NLS equation with harmonic trap for all 0 < β < 3/4.
AU - Lewin, Mathieu
AU - Nam, Phan
AU - Rougerie, Nicolas
ID - 632
IS - 6
JF - Proceedings of the American Mathematical Society
TI - A note on 2D focusing many boson systems
VL - 145
ER -
TY - CONF
AB - A Rapidly-exploring Random Tree (RRT) is an algorithm which can search a non-convex region of space by incrementally building a space-filling tree. The tree is constructed from random points drawn from system’s state space and is biased to grow towards large unexplored areas in the system. RRT can provide better coverage of a system’s possible behaviors compared with random simulations, but is more lightweight than full reachability analysis. In this paper, we explore some of the design decisions encountered while implementing a hybrid extension of the RRT algorithm, which have not been elaborated on before. In particular, we focus on handling non-determinism, which arises due to discrete transitions. We introduce the notion of important points to account for this phenomena. We showcase our ideas using heater and navigation benchmarks.
AU - Bak, Stanley
AU - Bogomolov, Sergiy
AU - Henzinger, Thomas A
AU - Kumar, Aviral
ED - Abate, Alessandro
ED - Bodo, Sylvie
ID - 633
SN - 978-331963500-2
TI - Challenges and tool implementation of hybrid rapidly exploring random trees
VL - 10381
ER -
TY - CHAP
AB - As autism spectrum disorder (ASD) is largely regarded as a neurodevelopmental condition, long-time consensus was that its hallmark features are irreversible. However, several studies from recent years using defined mouse models of ASD have provided clear evidence that in mice neurobiological and behavioural alterations can be ameliorated or even reversed by genetic restoration or pharmacological treatment either before or after symptom onset. Here, we review findings on genetic and pharmacological reversibility of phenotypes in mouse models of ASD. Our review should give a comprehensive overview on both aspects and encourage future studies to better understand the underlying molecular mechanisms that might be translatable from animals to humans.
AU - Schroeder, Jan
AU - Deliu, Elena
AU - Novarino, Gaia
AU - Schmeisser, Michael
ED - Schmeisser, Michael
ED - Boekers, Tobias
ID - 634
T2 - Translational Anatomy and Cell Biology of Autism Spectrum Disorder
TI - Genetic and pharmacological reversibility of phenotypes in mouse models of autism spectrum disorder
VL - 224
ER -
TY - CONF
AB - Memory-hard functions (MHFs) are hash algorithms whose evaluation cost is dominated by memory cost. As memory, unlike computation, costs about the same across different platforms, MHFs cannot be evaluated at significantly lower cost on dedicated hardware like ASICs. MHFs have found widespread applications including password hashing, key derivation, and proofs-of-work. This paper focuses on scrypt, a simple candidate MHF designed by Percival, and described in RFC 7914. It has been used within a number of cryptocurrencies (e.g., Litecoin and Dogecoin) and has been an inspiration for Argon2d, one of the winners of the recent password-hashing competition. Despite its popularity, no rigorous lower bounds on its memory complexity are known. We prove that scrypt is optimally memory-hard, i.e., its cumulative memory complexity (cmc) in the parallel random oracle model is Ω(n2w), where w and n are the output length and number of invocations of the underlying hash function, respectively. High cmc is a strong security target for MHFs introduced by Alwen and Serbinenko (STOC’15) which implies high memory cost even for adversaries who can amortize the cost over many evaluations and evaluate the underlying hash functions many times in parallel. Our proof is the first showing optimal memory-hardness for any MHF. Our result improves both quantitatively and qualitatively upon the recent work by Alwen et al. (EUROCRYPT’16) who proved a weaker lower bound of Ω(n2w/ log2 n) for a restricted class of adversaries.
AU - Alwen, Joel F
AU - Chen, Binchi
AU - Pietrzak, Krzysztof Z
AU - Reyzin, Leonid
AU - Tessaro, Stefano
ED - Coron, Jean-Sébastien
ED - Buus Nielsen, Jesper
ID - 635
SN - 978-331956616-0
TI - Scrypt is maximally memory hard
VL - 10212
ER -
TY - CONF
AB - Signal regular expressions can specify sequential properties of real-valued signals based on threshold conditions, regular operations, and duration constraints. In this paper we endow them with a quantitative semantics which indicates how robustly a signal matches or does not match a given expression. First, we show that this semantics is a safe approximation of a distance between the signal and the language defined by the expression. Then, we consider the robust matching problem, that is, computing the quantitative semantics of every segment of a given signal relative to an expression. We present an algorithm that solves this problem for piecewise-constant and piecewise-linear signals and show that for such signals the robustness map is a piecewise-linear function. The availability of an indicator describing how robustly a signal segment matches some regular pattern provides a general framework for quantitative monitoring of cyber-physical systems.
AU - Bakhirkin, Alexey
AU - Ferrere, Thomas
AU - Maler, Oded
AU - Ulus, Dogan
ED - Abate, Alessandro
ED - Geeraerts, Gilles
ID - 636
SN - 978-331965764-6
TI - On the quantitative semantics of regular expressions over real-valued signals
VL - 10419
ER -
TY - CONF
AB - For many cryptographic primitives, it is relatively easy to achieve selective security (where the adversary commits a-priori to some of the choices to be made later in the attack) but appears difficult to achieve the more natural notion of adaptive security (where the adversary can make all choices on the go as the attack progresses). A series of several recent works shows how to cleverly achieve adaptive security in several such scenarios including generalized selective decryption (Panjwani, TCC ’07 and Fuchsbauer et al., CRYPTO ’15), constrained PRFs (Fuchsbauer et al., ASIACRYPT ’14), and Yao garbled circuits (Jafargholi and Wichs, TCC ’16b). Although the above works expressed vague intuition that they share a common technique, the connection was never made precise. In this work we present a new framework that connects all of these works and allows us to present them in a unified and simplified fashion. Moreover, we use the framework to derive a new result for adaptively secure secret sharing over access structures defined via monotone circuits. We envision that further applications will follow in the future. Underlying our framework is the following simple idea. It is well known that selective security, where the adversary commits to n-bits of information about his future choices, automatically implies adaptive security at the cost of amplifying the adversary’s advantage by a factor of up to 2n. However, in some cases the proof of selective security proceeds via a sequence of hybrids, where each pair of adjacent hybrids locally only requires some smaller partial information consisting of m ≪ n bits. The partial information needed might be completely different between different pairs of hybrids, and if we look across all the hybrids we might rely on the entire n-bit commitment. Nevertheless, the above is sufficient to prove adaptive security, at the cost of amplifying the adversary’s advantage by a factor of only 2m ≪ 2n. In all of our examples using the above framework, the different hybrids are captured by some sort of a graph pebbling game and the amount of information that the adversary needs to commit to in each pair of hybrids is bounded by the maximum number of pebbles in play at any point in time. Therefore, coming up with better strategies for proving adaptive security translates to various pebbling strategies for different types of graphs.
AU - Jafargholi, Zahra
AU - Kamath Hosdurg, Chethan
AU - Klein, Karen
AU - Komargodski, Ilan
AU - Pietrzak, Krzysztof Z
AU - Wichs, Daniel
ED - Katz, Jonathan
ED - Shacham, Hovav
ID - 637
SN - 978-331963687-0
TI - Be adaptive avoid overcommitting
VL - 10401
ER -
TY - CONF
AB - Data-independent Memory Hard Functions (iMHFS) are finding a growing number of applications in security; especially in the domain of password hashing. An important property of a concrete iMHF is specified by fixing a directed acyclic graph (DAG) Gn on n nodes. The quality of that iMHF is then captured by the following two pebbling complexities of Gn: – The parallel cumulative pebbling complexity Π∥cc(Gn) must be as high as possible (to ensure that the amortized cost of computing the function on dedicated hardware is dominated by the cost of memory). – The sequential space-time pebbling complexity Πst(Gn) should be as close as possible to Π∥cc(Gn) (to ensure that using many cores in parallel and amortizing over many instances does not give much of an advantage). In this paper we construct a family of DAGs with best possible parameters in an asymptotic sense, i.e., where Π∥cc(Gn) = Ω(n2/ log(n)) (which matches a known upper bound) and Πst(Gn) is within a constant factor of Π∥cc(Gn). Our analysis relies on a new connection between the pebbling complexity of a DAG and its depth-robustness (DR) – a well studied combinatorial property. We show that high DR is sufficient for high Π∥cc. Alwen and Blocki (CRYPTO’16) showed that high DR is necessary and so, together, these results fully characterize DAGs with high Π∥cc in terms of DR. Complementing these results, we provide new upper and lower bounds on the Π∥cc of several important candidate iMHFs from the literature. We give the first lower bounds on the memory hardness of the Catena and Balloon Hashing functions in a parallel model of computation and we give the first lower bounds of any kind for (a version) of Argon2i. Finally we describe a new class of pebbling attacks improving on those of Alwen and Blocki (CRYPTO’16). By instantiating these attacks we upperbound the Π∥cc of the Password Hashing Competition winner Argon2i and one of the Balloon Hashing functions by O (n1.71). We also show an upper bound of O(n1.625) for the Catena functions and the two remaining Balloon Hashing functions.
AU - Alwen, Joel F
AU - Blocki, Jeremiah
AU - Pietrzak, Krzysztof Z
ED - Coron, Jean-Sébastien
ED - Buus Nielsen, Jesper
ID - 640
SN - 978-331956616-0
TI - Depth-robust graphs and their cumulative memory complexity
VL - 10212
ER -
TY - CONF
AB - We introduce two novel methods for learning parameters of graphical models for image labelling. The following two tasks underline both methods: (i) perturb model parameters based on given features and ground truth labelings, so as to exactly reproduce these labelings as optima of the local polytope relaxation of the labelling problem; (ii) train a predictor for the perturbed model parameters so that improved model parameters can be applied to the labelling of novel data. Our first method implements task (i) by inverse linear programming and task (ii) using a regressor e.g. a Gaussian process. Our second approach simultaneously solves tasks (i) and (ii) in a joint manner, while being restricted to linearly parameterised predictors. Experiments demonstrate the merits of both approaches.
AU - Trajkovska, Vera
AU - Swoboda, Paul
AU - Åström, Freddie
AU - Petra, Stefanie
ED - Lauze, François
ED - Dong, Yiqiu
ED - Bjorholm Dahl, Anders
ID - 641
SN - 978-331958770-7
TI - Graphical model parameter learning by inverse linear programming
VL - 10302
ER -
TY - JOUR
AB - Cauchy problems with SPDEs on the whole space are localized to Cauchy problems on a ball of radius R. This localization reduces various kinds of spatial approximation schemes to finite dimensional problems. The error is shown to be exponentially small. As an application, a numerical scheme is presented which combines the localization and the space and time discretization, and thus is fully implementable.
AU - Gerencser, Mate
AU - Gyöngy, István
ID - 642
IS - 307
JF - Mathematics of Computation
SN - 00255718
TI - Localization errors in solving stochastic partial differential equations in the whole space
VL - 86
ER -
TY - GEN
AB - Synchronous programs are easy to specify because the side effects of an operation are finished by the time the invocation of the operation returns to the caller. Asynchronous programs, on the other hand, are difficult to specify because there are side effects due to pending computation scheduled as a result of the invocation of an operation. They are also difficult to verify because of the large number of possible interleavings of concurrent asynchronous computation threads. We show that specifications and correctness proofs for asynchronous programs can be structured by introducing the fiction, for proof purposes, that intermediate, non-quiescent states of asynchronous operations can be ignored. Then, the task of specification becomes relatively simple and the task of verification can be naturally decomposed into smaller sub-tasks. The sub-tasks iteratively summarize, guided by the structure of an asynchronous program, the atomic effect of non-atomic operations and the synchronous effect of asynchronous operations. This structuring of specifications and proofs corresponds to the introduction of multiple layers of stepwise refinement for asynchronous programs. We present the first proof rule, called synchronization, to reduce asynchronous invocations on a lower layer to synchronous invocations on a higher layer. We implemented our proof method in CIVL and evaluated it on a collection of benchmark programs.
AU - Henzinger, Thomas A
AU - Kragl, Bernhard
AU - Qadeer, Shaz
ID - 6426
SN - 2664-1690
TI - Synchronizing the asynchronous
ER -
TY - JOUR
AB - It has been reported that nicotinamide-overload induces oxidative stress associated with insulin resistance, the key feature of type 2 diabetes mellitus (T2DM). This study aimed to investigate the effects of B vitamins in T2DM. Glucose tolerance tests (GTT) were carried out in adult Sprague-Dawley rats treated with or without cumulative doses of B vitamins. More specifically, insulin tolerance tests (ITT) were also carried out in adult Sprague-Dawley rats treated with or without cumulative doses of Vitamin B3. We found that cumulative Vitamin B1 and Vitamin B3 administration significantly increased the plasma H2O2 levels associated with high insulin levels. Only Vitamin B3 reduced muscular and hepatic glycogen contents. Cumulative administration of nicotinic acid, another form of Vitamin B3, also significantly increased plasma insulin level and H2O2 generation. Moreover, cumulative administration of nicotinic acid or nicotinamide impaired glucose metabolism. This study suggested that excess Vitamin B1 and Vitamin B3 caused oxidative stress and insulin resistance.
AU - Sun, Wuping
AU - Zhai, Ming-Zhu
AU - Zhou, Qian
AU - Qian, Chengrui
AU - Jiang, Changyu
ID - 643
IS - 4
JF - Chinese Journal of Physiology
SN - 03044920
TI - Effects of B vitamins overload on plasma insulin level and hydrogen peroxide generation in rats
VL - 60
ER -
TY - JOUR
AB - An instance of the valued constraint satisfaction problem (VCSP) is given by a finite set of variables, a finite domain of labels, and a sum of functions, each function depending on a subset of the variables. Each function can take finite values specifying costs of assignments of labels to its variables or the infinite value, which indicates an infeasible assignment. The goal is to find an assignment of labels to the variables that minimizes the sum. We study, assuming that P 6= NP, how the complexity of this very general problem depends on the set of functions allowed in the instances, the so-called constraint language. The case when all allowed functions take values in f0;1g corresponds to ordinary CSPs, where one deals only with the feasibility issue, and there is no optimization. This case is the subject of the algebraic CSP dichotomy conjecture predicting for which constraint languages CSPs are tractable (i.e., solvable in polynomial time) and for which they are NP-hard. The case when all allowed functions take only finite values corresponds to a finitevalued CSP, where the feasibility aspect is trivial and one deals only with the optimization issue. The complexity of finite-valued CSPs was fully classified by Thapper and Živný. An algebraic necessary condition for tractability of a general-valued CSP with a fixed constraint language was recently given by Kozik and Ochremiak. As our main result, we prove that if a constraint language satisfies this algebraic necessary condition, and the feasibility CSP (i.e., the problem of deciding whether a given instance has a feasible solution) corresponding to the VCSP with this language is tractable, then the VCSP is tractable. The algorithm is a simple combination of the assumed algorithm for the feasibility CSP and the standard LP relaxation. As a corollary, we obtain that a dichotomy for ordinary CSPs would imply a dichotomy for general-valued CSPs.
AU - Kolmogorov, Vladimir
AU - Krokhin, Andrei
AU - Rolinek, Michal
ID - 644
IS - 3
JF - SIAM Journal on Computing
TI - The complexity of general-valued CSPs
VL - 46
ER -
TY - CONF
AB - Markov decision processes (MDPs) are standard models for probabilistic systems with non-deterministic behaviours. Long-run average rewards provide a mathematically elegant formalism for expressing long term performance. Value iteration (VI) is one of the simplest and most efficient algorithmic approaches to MDPs with other properties, such as reachability objectives. Unfortunately, a naive extension of VI does not work for MDPs with long-run average rewards, as there is no known stopping criterion. In this work our contributions are threefold. (1) We refute a conjecture related to stopping criteria for MDPs with long-run average rewards. (2) We present two practical algorithms for MDPs with long-run average rewards based on VI. First, we show that a combination of applying VI locally for each maximal end-component (MEC) and VI for reachability objectives can provide approximation guarantees. Second, extending the above approach with a simulation-guided on-demand variant of VI, we present an anytime algorithm that is able to deal with very large models. (3) Finally, we present experimental results showing that our methods significantly outperform the standard approaches on several benchmarks.
AU - Ashok, Pranav
AU - Chatterjee, Krishnendu
AU - Daca, Przemyslaw
AU - Kretinsky, Jan
AU - Meggendorfer, Tobias
ED - Majumdar, Rupak
ED - Kunčak, Viktor
ID - 645
SN - 978-331963386-2
TI - Value iteration for long run average reward in markov decision processes
VL - 10426
ER -
TY - CONF
AB - We present a novel convex relaxation and a corresponding inference algorithm for the non-binary discrete tomography problem, that is, reconstructing discrete-valued images from few linear measurements. In contrast to state of the art approaches that split the problem into a continuous reconstruction problem for the linear measurement constraints and a discrete labeling problem to enforce discrete-valued reconstructions, we propose a joint formulation that addresses both problems simultaneously, resulting in a tighter convex relaxation. For this purpose a constrained graphical model is set up and evaluated using a novel relaxation optimized by dual decomposition. We evaluate our approach experimentally and show superior solutions both mathematically (tighter relaxation) and experimentally in comparison to previously proposed relaxations.
AU - Kuske, Jan
AU - Swoboda, Paul
AU - Petra, Stefanie
ED - Lauze, François
ED - Dong, Yiqiu
ED - Bjorholm Dahl, Anders
ID - 646
SN - 978-331958770-7
TI - A novel convex relaxation for non binary discrete tomography
VL - 10302
ER -
TY - CONF
AB - Despite researchers’ efforts in the last couple of decades, reachability analysis is still a challenging problem even for linear hybrid systems. Among the existing approaches, the most practical ones are mainly based on bounded-time reachable set over-approximations. For the purpose of unbounded-time analysis, one important strategy is to abstract the original system and find an invariant for the abstraction. In this paper, we propose an approach to constructing a new kind of abstraction called conic abstraction for affine hybrid systems, and to computing reachable sets based on this abstraction. The essential feature of a conic abstraction is that it partitions the state space of a system into a set of convex polyhedral cones which is derived from a uniform conic partition of the derivative space. Such a set of polyhedral cones is able to cut all trajectories of the system into almost straight segments so that every segment of a reach pipe in a polyhedral cone tends to be straight as well, and hence can be over-approximated tightly by polyhedra using similar techniques as HyTech or PHAVer. In particular, for diagonalizable affine systems, our approach can guarantee to find an invariant for unbounded reachable sets, which is beyond the capability of bounded-time reachability analysis tools. We implemented the approach in a tool and experiments on benchmarks show that our approach is more powerful than SpaceEx and PHAVer in dealing with diagonalizable systems.
AU - Bogomolov, Sergiy
AU - Giacobbe, Mirco
AU - Henzinger, Thomas A
AU - Kong, Hui
ID - 647
SN - 978-331965764-6
TI - Conic abstractions for hybrid systems
VL - 10419
ER -
TY - CONF
AB - Pseudoentropy has found a lot of important applications to cryptography and complexity theory. In this paper we focus on the foundational problem that has not been investigated so far, namely by how much pseudoentropy (the amount seen by computationally bounded attackers) diﬀers from its information-theoretic counterpart (seen by unbounded observers), given certain limits on attacker’s computational power? We provide the following answer for HILL pseudoentropy, which exhibits a threshold behavior around the size exponential in the entropy amount:– If the attacker size (s) and advantage () satisfy s (formula presented) where k is the claimed amount of pseudoentropy, then the pseudoentropy boils down to the information-theoretic smooth entropy. – If s (formula presented) then pseudoentropy could be arbitrarily bigger than the information-theoretic smooth entropy. Besides answering the posted question, we show an elegant application of our result to the complexity theory, namely that it implies the clas-sical result on the existence of functions hard to approximate (due to Pippenger). In our approach we utilize non-constructive techniques: the duality of linear programming and the probabilistic method.
AU - Skórski, Maciej
ED - Jäger, Gerhard
ED - Steila, Silvia
ID - 648
SN - 978-331955910-0
TI - On the complexity of breaking pseudoentropy
VL - 10185
ER -
TY - CONF
AB - In this work we present a short and unified proof for the Strong and Weak Regularity Lemma, based on the cryptographic tech-nique called low-complexity approximations. In short, both problems reduce to a task of finding constructively an approximation for a certain target function under a class of distinguishers (test functions), where dis-tinguishers are combinations of simple rectangle-indicators. In our case these approximations can be learned by a simple iterative procedure, which yields a unified and simple proof, achieving for any graph with density d and any approximation parameter the partition size. The novelty in our proof is: (a) a simple approach which yields both strong and weaker variant, and (b) improvements when d = o(1). At an abstract level, our proof can be seen a refinement and simplification of the “analytic” proof given by Lovasz and Szegedy.
AU - Skórski, Maciej
ED - Jäger, Gerhard
ED - Steila, Silvia
ID - 650
SN - 03029743
TI - A cryptographic view of regularity lemmas: Simpler unified proofs and refined bounds
VL - 10185
ER -
TY - JOUR
AB - Superhydrophobic surfaces reduce the frictional drag between water and solid materials, but this effect is often temporary. The realization of sustained drag reduction has applications for water vehicles and pipeline flows.
AU - Hof, Björn
ID - 651
IS - 7636
JF - Nature
SN - 00280836
TI - Fluid dynamics: Water flows out of touch
VL - 541
ER -
TY - CONF
AB - A (possibly degenerate) drawing of a graph G in the plane is approximable by an embedding if it can be turned into an embedding by an arbitrarily small perturbation. We show that testing, whether a drawing of a planar graph G in the plane is approximable by an embedding, can be carried out in polynomial time, if a desired embedding of G belongs to a fixed isotopy class, i.e., the rotation system (or equivalently the faces) of the embedding of G and the choice of outer face are fixed. In other words, we show that c-planarity with embedded pipes is tractable for graphs with fixed embeddings. To the best of our knowledge an analogous result was previously known essentially only when G is a cycle.
AU - Fulek, Radoslav
ID - 6517
TI - Embedding graphs into embedded graphs
VL - 92
ER -
TY - CONF
AB - We present an approach that enables robots to self-organize their sensorimotor behavior from scratch without providing specific information about neither the robot nor its environment. This is achieved by a simple neural control law that increases the consistency between external sensor dynamics and internal neural dynamics of the utterly simple controller. In this way, the embodiment and the agent-environment coupling are the only source of individual development. We show how an anthropomorphic tendon driven arm-shoulder system develops different behaviors depending on that coupling. For instance: Given a bottle half-filled with water, the arm starts to shake it, driven by the physical response of the water. When attaching a brush, the arm can be manipulated into wiping a table, and when connected to a revolvable wheel it finds out how to rotate it. Thus, the robot may be said to discover the affordances of the world. When allowing two (simulated) humanoid robots to interact physically, they engage into a joint behavior development leading to, for instance, spontaneous cooperation. More social effects are observed if the robots can visually perceive each other. Although, as an observer, it is tempting to attribute an apparent intentionality, there is nothing of the kind put in. As a conclusion, we argue that emergent behavior may be much less rooted in explicit intentions, internal motivations, or specific reward systems than is commonly believed.
AU - Der, Ralf
AU - Martius, Georg S
ID - 652
SN - 978-150905069-7
TI - Dynamical self consistency leads to behavioral development and emergent social interactions in robots
ER -
TY - CONF
AB - This paper studies the complexity of estimating Rényi divergences of discrete distributions: p observed from samples and the baseline distribution q known a priori. Extending the results of Acharya et al. (SODA'15) on estimating Rényi entropy, we present improved estimation techniques together with upper and lower bounds on the sample complexity. We show that, contrarily to estimating Rényi entropy where a sublinear (in the alphabet size) number of samples suffices, the sample complexity is heavily dependent on events occurring unlikely in q, and is unbounded in general (no matter what an estimation technique is used). For any divergence of integer order bigger than 1, we provide upper and lower bounds on the number of samples dependent on probabilities of p and q (the lower bounds hold for non-integer orders as well). We conclude that the worst-case sample complexity is polynomial in the alphabet size if and only if the probabilities of q are non-negligible. This gives theoretical insights into heuristics used in the applied literature to handle numerical instability, which occurs for small probabilities of q. Our result shows that they should be handled with care not only because of numerical issues, but also because of a blow up in the sample complexity.
AU - Skórski, Maciej
ID - 6526
SN - 9781509040964
T2 - 2017 IEEE International Symposium on Information Theory (ISIT)
TI - On the complexity of estimating Rènyi divergences
ER -
TY - CONF
AB - A memory-hard function (MHF) ƒn with parameter n can be computed in sequential time and space n. Simultaneously, a high amortized parallel area-time complexity (aAT) is incurred per evaluation. In practice, MHFs are used to limit the rate at which an adversary (using a custom computational device) can evaluate a security sensitive function that still occasionally needs to be evaluated by honest users (using an off-the-shelf general purpose device). The most prevalent examples of such sensitive functions are Key Derivation Functions (KDFs) and password hashing algorithms where rate limits help mitigate off-line dictionary attacks. As the honest users' inputs to these functions are often (low-entropy) passwords special attention is given to a class of side-channel resistant MHFs called iMHFs.
Essentially all iMHFs can be viewed as some mode of operation (making n calls to some round function) given by a directed acyclic graph (DAG) with very low indegree. Recently, a combinatorial property of a DAG has been identified (called "depth-robustness") which results in good provable security for an iMHF based on that DAG. Depth-robust DAGs have also proven useful in other cryptographic applications. Unfortunately, up till now, all known very depth-robust DAGs are impractically complicated and little is known about their exact (i.e. non-asymptotic) depth-robustness both in theory and in practice.
In this work we build and analyze (both formally and empirically) several exceedingly simple and efficient to navigate practical DAGs for use in iMHFs and other applications. For each DAG we:
*Prove that their depth-robustness is asymptotically maximal.
*Prove bounds of at least 3 orders of magnitude better on their exact depth-robustness compared to known bounds for other practical iMHF.
*Implement and empirically evaluate their depth-robustness and aAT against a variety of state-of-the art (and several new) depth-reduction and low aAT attacks.
We find that, against all attacks, the new DAGs perform significantly better in practice than Argon2i, the most widely deployed iMHF in practice.
Along the way we also improve the best known empirical attacks on the aAT of Argon2i by implementing and testing several heuristic versions of a (hitherto purely theoretical) depth-reduction attack. Finally, we demonstrate practicality of our constructions by modifying the Argon2i code base to use one of the new high aAT DAGs. Experimental benchmarks on a standard off-the-shelf CPU show that the new modifications do not adversely affect the impressive throughput of Argon2i (despite seemingly enjoying significantly higher aAT).
AU - Alwen, Joel F
AU - Blocki, Jeremiah
AU - Harsha, Ben
ID - 6527
SN - 9781450349468
T2 - Proceedings of the 2017 ACM SIGSAC Conference on Computer and Communications Security
TI - Practical graphs for optimal side-channel resistant memory-hard functions
ER -
TY - JOUR
AB - In November 2016, developmental biologists, synthetic biologists and engineers gathered in Paris for a meeting called ‘Engineering the embryo’. The participants shared an interest in exploring how synthetic systems can reveal new principles of embryonic development, and how the in vitro manipulation and modeling of development using stem cells can be used to integrate ideas and expertise from physics, developmental biology and tissue engineering. As we review here, the conference pinpointed some of the challenges arising at the intersection of these fields, along with great enthusiasm for finding new approaches and collaborations.
AU - Kicheva, Anna
AU - Rivron, Nicolas
ID - 654
IS - 5
JF - Development
SN - 09501991
TI - Creating to understand – developmental biology meets engineering in Paris
VL - 144
ER -
TY - JOUR
AB - The bacterial flagellum is a self-assembling nanomachine. The external flagellar filament, several times longer than a bacterial cell body, is made of a few tens of thousands subunits of a single protein: flagellin. A fundamental problem concerns the molecular mechanism of how the flagellum grows outside the cell, where no discernible energy source is available. Here, we monitored the dynamic assembly of individual flagella using in situ labelling and real-time immunostaining of elongating flagellar filaments. We report that the rate of flagellum growth, initially ~1,700 amino acids per second, decreases with length and that the previously proposed chain mechanism does not contribute to the filament elongation dynamics. Inhibition of the proton motive force-dependent export apparatus revealed a major contribution of substrate injection in driving filament elongation. The combination of experimental and mathematical evidence demonstrates that a simple, injection-diffusion mechanism controls bacterial flagella growth outside the cell.
AU - Renault, Thibaud
AU - Abraham, Anthony
AU - Bergmiller, Tobias
AU - Paradis, Guillaume
AU - Rainville, Simon
AU - Charpentier, Emmanuelle
AU - Guet, Calin C
AU - Tu, Yuhai
AU - Namba, Keiichi
AU - Keener, James
AU - Minamino, Tohru
AU - Erhardt, Marc
ID - 655
JF - eLife
SN - 2050084X
TI - Bacterial flagella grow through an injection diffusion mechanism
VL - 6
ER -
TY - JOUR
AB - Human neurons transplanted into a mouse model for Alzheimer’s disease show human-specific vulnerability to β-amyloid plaques and may help to identify new therapeutic targets.
AU - Novarino, Gaia
ID - 656
IS - 381
JF - Science Translational Medicine
SN - 19466234
TI - Modeling Alzheimer's disease in mice with human neurons
VL - 9
ER -
TY - JOUR
AB - Plant organs are typically organized into three main tissue layers. The middle ground tissue layer comprises the majority of the plant body and serves a wide range of functions, including photosynthesis, selective nutrient uptake and storage, and gravity sensing. Ground tissue patterning and maintenance in Arabidopsis are controlled by a well-established gene network revolving around the key regulator SHORT-ROOT (SHR). In contrast, it is completely unknown how ground tissue identity is first specified from totipotent precursor cells in the embryo. The plant signaling molecule auxin, acting through AUXIN RESPONSE FACTOR (ARF) transcription factors, is critical for embryo patterning. The auxin effector ARF5/MONOPTEROS (MP) acts both cell-autonomously and noncell-autonomously to control embryonic vascular tissue formation and root initiation, respectively. Here we show that auxin response and ARF activity cell-autonomously control the asymmetric division of the first ground tissue cells. By identifying embryonic target genes, we show that MP transcriptionally initiates the ground tissue lineage and acts upstream of the regulatory network that controls ground tissue patterning and maintenance. Strikingly, whereas the SHR network depends on MP, this MP function is, at least in part, SHR independent. Our study therefore identifies auxin response as a regulator of ground tissue specification in the embryonic root, and reveals that ground tissue initiation and maintenance use different regulators and mechanisms. Moreover, our data provide a framework for the simultaneous formation of multiple cell types by the same transcriptional regulator.
AU - Möller, Barbara
AU - Ten Hove, Colette
AU - Xiang, Daoquan
AU - Williams, Nerys
AU - López, Lorena
AU - Yoshida, Saiko
AU - Smit, Margot
AU - Datla, Raju
AU - Weijers, Dolf
ID - 657
IS - 12
JF - PNAS
SN - 00278424
TI - Auxin response cell autonomously controls ground tissue initiation in the early arabidopsis embryo
VL - 114
ER -
TY - JOUR
AB - With the accelerated development of robot technologies, control becomes one of the central themes of research. In traditional approaches, the controller, by its internal functionality, finds appropriate actions on the basis of specific objectives for the task at hand. While very successful in many applications, self-organized control schemes seem to be favored in large complex systems with unknown dynamics or which are difficult to model. Reasons are the expected scalability, robustness, and resilience of self-organizing systems. The paper presents a self-learning neurocontroller based on extrinsic differential plasticity introduced recently, applying it to an anthropomorphic musculoskeletal robot arm with attached objects of unknown physical dynamics. The central finding of the paper is the following effect: by the mere feedback through the internal dynamics of the object, the robot is learning to relate each of the objects with a very specific sensorimotor pattern. Specifically, an attached pendulum pilots the arm into a circular motion, a half-filled bottle produces axis oriented shaking behavior, a wheel is getting rotated, and wiping patterns emerge automatically in a table-plus-brush setting. By these object-specific dynamical patterns, the robot may be said to recognize the object's identity, or in other words, it discovers dynamical affordances of objects. Furthermore, when including hand coordinates obtained from a camera, a dedicated hand-eye coordination self-organizes spontaneously. These phenomena are discussed from a specific dynamical system perspective. Central is the dedicated working regime at the border to instability with its potentially infinite reservoir of (limit cycle) attractors "waiting" to be excited. Besides converging toward one of these attractors, variate behavior is also arising from a self-induced attractor morphing driven by the learning rule. We claim that experimental investigations with this anthropomorphic, self-learning robot not only generate interesting and potentially useful behaviors, but may also help to better understand what subjective human muscle feelings are, how they can be rooted in sensorimotor patterns, and how these concepts may feed back on robotics.
AU - Der, Ralf
AU - Martius, Georg S
ID - 658
IS - MAR
JF - Frontiers in Neurorobotics
SN - 16625218
TI - Self organized behavior generation for musculoskeletal robots
VL - 11
ER -
TY - JOUR
AB - Migration frequently involves Rac-mediated protrusion of lamellipodia, formed by Arp2/3 complex-dependent branching thought to be crucial for force generation and stability of these networks. The formins FMNL2 and FMNL3 are Cdc42 effectors targeting to the lamellipodium tip and shown here to nucleate and elongate actin filaments with complementary activities in vitro. In migrating B16-F1 melanoma cells, both formins contribute to the velocity of lamellipodium protrusion. Loss of FMNL2/3 function in melanoma cells and fibroblasts reduces lamellipodial width, actin filament density and -bundling, without changing patterns of Arp2/3 complex incorporation. Strikingly, in melanoma cells, FMNL2/3 gene inactivation almost completely abolishes protrusion forces exerted by lamellipodia and modifies their ultrastructural organization. Consistently, CRISPR/Cas-mediated depletion of FMNL2/3 in fibroblasts reduces both migration and capability of cells to move against viscous media. Together, we conclude that force generation in lamellipodia strongly depends on FMNL formin activity, operating in addition to Arp2/3 complex-dependent filament branching.
AU - Kage, Frieda
AU - Winterhoff, Moritz
AU - Dimchev, Vanessa
AU - Müller, Jan
AU - Thalheim, Tobias
AU - Freise, Anika
AU - Brühmann, Stefan
AU - Kollasser, Jana
AU - Block, Jennifer
AU - Dimchev, Georgi A
AU - Geyer, Matthias
AU - Schnittler, Hams
AU - Brakebusch, Cord
AU - Stradal, Theresia
AU - Carlier, Marie
AU - Sixt, Michael K
AU - Käs, Josef
AU - Faix, Jan
AU - Rottner, Klemens
ID - 659
JF - Nature Communications
SN - 20411723
TI - FMNL formins boost lamellipodial force generation
VL - 8
ER -
TY - JOUR
AB - Growing microtubules are protected from depolymerization by the presence of a GTP or GDP/Pi cap. End-binding proteins of the EB1 family bind to the stabilizing cap, allowing monitoring of its size in real time. The cap size has been shown to correlate with instantaneous microtubule stability. Here we have quantitatively characterized the properties of cap size fluctuations during steadystate growth and have developed a theory predicting their timescale and amplitude from the kinetics of microtubule growth and cap maturation. In contrast to growth speed fluctuations, cap size fluctuations show a characteristic timescale, which is defined by the lifetime of the cap sites. Growth fluctuations affect the amplitude of cap size fluctuations; however, cap size does not affect growth speed, indicating that microtubules are far from instability during most of their time of growth. Our theory provides the basis for a quantitative understanding of microtubule stability fluctuations during steady-state growth.
AU - Rickman, Jamie
AU - Düllberg, Christian F
AU - Cade, Nicholas
AU - Griffin, Lewis
AU - Surrey, Thomas
ID - 660
IS - 13
JF - PNAS
SN - 00278424
TI - Steady state EB cap size fluctuations are determined by stochastic microtubule growth and maturation
VL - 114
ER -
TY - JOUR
AB - We report a direct-numerical-simulation study of the Taylor-Couette flow in the quasi-Keplerian regime at shear Reynolds numbers up to (105). Quasi-Keplerian rotating flow has been investigated for decades as a simplified model system to study the origin of turbulence in accretion disks that is not fully understood. The flow in this study is axially periodic and thus the experimental end-wall effects on the stability of the flow are avoided. Using optimal linear perturbations as initial conditions, our simulations find no sustained turbulence: the strong initial perturbations distort the velocity profile and trigger turbulence that eventually decays.
AU - Shi, Liang
AU - Hof, Björn
AU - Rampp, Markus
AU - Avila, Marc
ID - 662
IS - 4
JF - Physics of Fluids
SN - 10706631
TI - Hydrodynamic turbulence in quasi Keplerian rotating flows
VL - 29
ER -
TY - CONF
AB - In this paper, we propose an approach to automatically compute invariant clusters for nonlinear semialgebraic hybrid systems. An invariant cluster for an ordinary differential equation (ODE) is a multivariate polynomial invariant g(u→, x→) = 0, parametric in u→, which can yield an infinite number of concrete invariants by assigning different values to u→ so that every trajectory of the system can be overapproximated precisely by the intersection of a group of concrete invariants. For semialgebraic systems, which involve ODEs with multivariate polynomial right-hand sides, given a template multivariate polynomial g(u→, x→), an invariant cluster can be obtained by first computing the remainder of the Lie derivative of g(u→, x→) divided by g(u→, x→) and then solving the system of polynomial equations obtained from the coefficients of the remainder. Based on invariant clusters and sum-of-squares (SOS) programming, we present a new method for the safety verification of hybrid systems. Experiments on nonlinear benchmark systems from biology and control theory show that our approach is efficient.
AU - Kong, Hui
AU - Bogomolov, Sergiy
AU - Schilling, Christian
AU - Jiang, Yu
AU - Henzinger, Thomas A
ID - 663
SN - 978-145034590-3
T2 - Proceedings of the 20th International Conference on Hybrid Systems
TI - Safety verification of nonlinear hybrid systems based on invariant clusters
ER -
TY - JOUR
AB - The molecular mechanisms underlying phenotypic variation in isogenic bacterial populations remain poorly understood.We report that AcrAB-TolC, the main multidrug efflux pump of Escherichia coli, exhibits a strong partitioning bias for old cell poles by a segregation mechanism that is mediated by ternary AcrAB-TolC complex formation. Mother cells inheriting old poles are phenotypically distinct and display increased drug efflux activity relative to daughters. Consequently, we find systematic and long-lived growth differences between mother and daughter cells in the presence of subinhibitory drug concentrations. A simple model for biased partitioning predicts a population structure of long-lived and highly heterogeneous phenotypes. This straightforward mechanism of generating sustained growth rate differences at subinhibitory antibiotic concentrations has implications for understanding the emergence of multidrug resistance in bacteria.
AU - Bergmiller, Tobias
AU - Andersson, Anna M
AU - Tomasek, Kathrin
AU - Balleza, Enrique
AU - Kiviet, Daniel
AU - Hauschild, Robert
AU - Tkacik, Gasper
AU - Guet, Calin C
ID - 665
IS - 6335
JF - Science
SN - 00368075
TI - Biased partitioning of the multidrug efflux pump AcrAB TolC underlies long lived phenotypic heterogeneity
VL - 356
ER -
TY - JOUR
AB - Antibiotics elicit drastic changes in microbial gene expression, including the induction of stress response genes. While certain stress responses are known to “cross-protect” bacteria from other stressors, it is unclear whether cellular responses to antibiotics have a similar protective role. By measuring the genome-wide transcriptional response dynamics of Escherichia coli to four antibiotics, we found that trimethoprim induces a rapid acid stress response that protects bacteria from subsequent exposure to acid. Combining microfluidics with time-lapse imaging to monitor survival and acid stress response in single cells revealed that the noisy expression of the acid resistance operon gadBC correlates with single-cell survival. Cells with higher gadBC expression following trimethoprim maintain higher intracellular pH and survive the acid stress longer. The seemingly random single-cell survival under acid stress can therefore be predicted from gadBC expression and rationalized in terms of GadB/C molecular function. Overall, we provide a roadmap for identifying the molecular mechanisms of single-cell cross-protection between antibiotics and other stressors.
AU - Mitosch, Karin
AU - Rieckh, Georg
AU - Bollenbach, Tobias
ID - 666
IS - 4
JF - Cell Systems
SN - 24054712
TI - Noisy response to antibiotic stress predicts subsequent single cell survival in an acidic environment
VL - 4
ER -
TY - JOUR
AB - Perinatal exposure to penicillin may result in longlasting gut and behavioral changes.
AU - Novarino, Gaia
ID - 667
IS - 387
JF - Science Translational Medicine
SN - 19466234
TI - The antisocial side of antibiotics
VL - 9
ER -
TY - CONF
AB - Polar codes represent one of the major recent breakthroughs in coding theory and, because of their attractive features, they have been selected for the incoming 5G standard. As such, a lot of attention has been devoted to the development of decoding algorithms with good error performance and efficient hardware implementation. One of the leading candidates in this regard is represented by successive-cancellation list (SCL) decoding. However, its hardware implementation requires a large amount of memory. Recently, a partitioned SCL (PSCL) decoder has been proposed to significantly reduce the memory consumption [1]. In this paper, we examine the paradigm of PSCL decoding from both theoretical and practical standpoints: (i) by changing the construction of the code, we are able to improve the performance at no additional computational, latency or memory cost, (ii) we present an optimal scheme to allocate cyclic redundancy checks (CRCs), and (iii) we provide an upper bound on the list size that allows MAP performance.
AU - Hashemi, Seyyed Ali
AU - Mondelli, Marco
AU - Hassani, Hamed
AU - Urbanke, Ruediger
AU - Gross, Warren
ID - 6679
T2 - 2017 IEEE Global Communications Conference
TI - Partitioned list decoding of polar codes: Analysis and improvement of finite length performance
ER -
TY - JOUR
AB - Macrophage filopodia, finger-like membrane protrusions, were first implicated in phagocytosis more than 100 years ago, but little is still known about the involvement of these actin-dependent structures in particle clearance. Using spinning disk confocal microscopy to image filopodial dynamics in mouse resident Lifeact-EGFP macrophages, we show that filopodia, or filopodia-like structures, support pathogen clearance by multiple means. Filopodia supported the phagocytic uptake of bacterial (Escherichia coli) particles by (i) capturing along the filopodial shaft and surfing toward the cell body, the most common mode of capture; (ii) capturing via the tip followed by retraction; (iii) combinations of surfing and retraction; or (iv) sweeping actions. In addition, filopodia supported the uptake of zymosan (Saccharomyces cerevisiae) particles by (i) providing fixation, (ii) capturing at the tip and filopodia-guided actin anterograde flow with phagocytic cup formation, and (iii) the rapid growth of new protrusions. To explore the role of filopodia-inducing Cdc42, we generated myeloid-restricted Cdc42 knock-out mice. Cdc42-deficient macrophages exhibited rapid phagocytic cup kinetics, but reduced particle clearance, which could be explained by the marked rounded-up morphology of these cells. Macrophages lacking Myo10, thought to act downstream of Cdc42, had normal morphology, motility, and phagocytic cup formation, but displayed markedly reduced filopodia formation. In conclusion, live-cell imaging revealed multiple mechanisms involving macrophage filopodia in particle capture and engulfment. Cdc42 is not critical for filopodia or phagocytic cup formation, but plays a key role in driving macrophage lamellipodial spreading.
AU - Horsthemke, Markus
AU - Bachg, Anne
AU - Groll, Katharina
AU - Moyzio, Sven
AU - Müther, Barbara
AU - Hemkemeyer, Sandra
AU - Wedlich Söldner, Roland
AU - Sixt, Michael K
AU - Tacke, Sebastian
AU - Bähler, Martin
AU - Hanley, Peter
ID - 668
IS - 17
JF - Journal of Biological Chemistry
SN - 00219258
TI - Multiple roles of filopodial dynamics in particle capture and phagocytosis and phenotypes of Cdc42 and Myo10 deletion
VL - 292
ER -
TY - JOUR
AB - The exocyst, a eukaryotic tethering complex, coregulates targeted exocytosis as an effector of small GTPases in polarized cell growth. In land plants, several exocyst subunits are encoded by double or triple paralogs, culminating in tens of EXO70 paralogs. Out of 23 Arabidopsis thaliana EXO70 isoforms, we analyzed seven isoforms expressed in pollen. Genetic and microscopic analyses of single mutants in EXO70A2, EXO70C1, EXO70C2, EXO70F1, EXO70H3, EXO70H5, and EXO70H6 genes revealed that only a loss-of-function EXO70C2 allele resulted in a significant male-specific transmission defect (segregation 40%:51%:9%) due to aberrant pollen tube growth. Mutant pollen tubes grown in vitro exhibited an enhanced growth rate and a decreased thickness of the tip cell wall, causing tip bursts. However, exo70C2 pollen tubes could frequently recover and restart their speedy elongation, resulting in a repetitive stop-and-go growth dynamics. A pollenspecific depletion of the closest paralog, EXO70C1, using artificial microRNA in the exo70C2 mutant background, resulted in a complete pollen-specific transmission defect, suggesting redundant functions of EXO70C1 and EXO70C2. Both EXO70C1 and EXO70C2, GFP tagged and expressed under the control of their native promoters, localized in the cytoplasm of pollen grains, pollen tubes, and also root trichoblast cells. The expression of EXO70C2-GFP complemented the aberrant growth of exo70C2 pollen tubes. The absent EXO70C2 interactions with core exocyst subunits in the yeast two-hybrid assay, cytoplasmic localization, and genetic effect suggest an unconventional EXO70 function possibly as a regulator of exocytosis outside the exocyst complex. In conclusion, EXO70C2 is a novel factor contributing to the regulation of optimal tip growth of Arabidopsis pollen tubes.
AU - Synek, Lukáš
AU - Vukašinović, Nemanja
AU - Kulich, Ivan
AU - Hála, Michal
AU - Aldorfová, Klára
AU - Fendrych, Matyas
AU - Žárský, Viktor
ID - 669
IS - 1
JF - Plant Physiology
SN - 00320889
TI - EXO70C2 is a key regulatory factor for optimal tip growth of pollen
VL - 174
ER -
TY - JOUR
AB - We propose an efficient method to model paper tearing in the context of interactive modeling. The method uses geometrical information to automatically detect potential starting points of tears. We further introduce a new hybrid geometrical and physical-based method to compute the trajectory of tears while procedurally synthesizing high resolution details of the tearing path using a texture based approach. The results obtained are compared with real paper and with previous studies on the expected geometric paths of paper that tears.
AU - Schreck, Camille
AU - Rohmer, Damien
AU - Hahmann, Stefanie
ID - 670
IS - 2
JF - Computer Graphics Forum
SN - 01677055
TI - Interactive paper tearing
VL - 36
ER -