TY - CHAP
AB - Cell division in prokaryotes and eukaryotes is commonly initiated by the well-controlled binding of proteins to the cytoplasmic side of the cell membrane. However, a precise characterization of the spatiotemporal dynamics of membrane-bound proteins is often difficult to achieve in vivo. Here, we present protocols for the use of supported lipid bilayers to rebuild the cytokinetic machineries of cells with greatly different dimensions: the bacterium Escherichia coli and eggs of the vertebrate Xenopus laevis. Combined with total internal reflection fluorescence microscopy, these experimental setups allow for precise quantitative analyses of membrane-bound proteins. The protocols described to obtain glass-supported membranes from bacterial and vertebrate lipids can be used as starting points for other reconstitution experiments. We believe that similar biochemical assays will be instrumental to study the biochemistry and biophysics underlying a variety of complex cellular tasks, such as signaling, vesicle trafficking, and cell motility.
AU - Nguyen, Phuong
AU - Field, Christine
AU - Groen, Aaron
AU - Mitchison, Timothy
AU - Loose, Martin
ID - 1544
T2 - Building a Cell from its Components Parts
TI - Using supported bilayers to study the spatiotemporal organization of membrane-bound proteins
VL - 128
ER -
TY - JOUR
AB - Synaptic efficacy and precision are influenced by the coupling of voltage-gated Ca2+ channels (VGCCs) to vesicles. But because the topography of VGCCs and their proximity to vesicles is unknown, a quantitative understanding of the determinants of vesicular release at nanometer scale is lacking. To investigate this, we combined freeze-fracture replica immunogold labeling of Cav2.1 channels, local [Ca2+] imaging, and patch pipette perfusion of EGTA at the calyx of Held. Between postnatal day 7 and 21, VGCCs formed variable sized clusters and vesicular release became less sensitive to EGTA, whereas fixed Ca2+ buffer properties remained constant. Experimentally constrained reaction-diffusion simulations suggest that Ca2+ sensors for vesicular release are located at the perimeter of VGCC clusters (<30nm) and predict that VGCC number per cluster determines vesicular release probability without altering release time course. This "perimeter release model" provides a unifying framework accounting for developmental changes in both synaptic efficacy and time course.
AU - Nakamura, Yukihiro
AU - Harada, Harumi
AU - Kamasawa, Naomi
AU - Matsui, Ko
AU - Rothman, Jason
AU - Shigemoto, Ryuichi
AU - Silver, R Angus
AU - Digregorio, David
AU - Takahashi, Tomoyuki
ID - 1546
IS - 1
JF - Neuron
TI - Nanoscale distribution of presynaptic Ca2+ channels and its impact on vesicular release during development
VL - 85
ER -
TY - JOUR
AB - Let G be a graph on the vertex set V(G) = {x1,…,xn} with the edge set E(G), and let R = K[x1,…, xn] be the polynomial ring over a field K. Two monomial ideals are associated to G, the edge ideal I(G) generated by all monomials xixj with {xi,xj} ∈ E(G), and the vertex cover ideal IG generated by monomials ∏xi∈Cxi for all minimal vertex covers C of G. A minimal vertex cover of G is a subset C ⊂ V(G) such that each edge has at least one vertex in C and no proper subset of C has the same property. Indeed, the vertex cover ideal of G is the Alexander dual of the edge ideal of G. In this paper, for an unmixed bipartite graph G we consider the lattice of vertex covers LG and we explicitly describe the minimal free resolution of the ideal associated to LG which is exactly the vertex cover ideal of G. Then we compute depth, projective dimension, regularity and extremal Betti numbers of R/I(G) in terms of the associated lattice.
AU - Mohammadi, Fatemeh
AU - Moradi, Somayeh
ID - 1547
IS - 3
JF - Bulletin of the Korean Mathematical Society
TI - Resolution of unmixed bipartite graphs
VL - 52
ER -
TY - JOUR
AB - Reproduction within a host and transmission to the next host are crucial for the virulence and fitness of pathogens. Nevertheless, basic knowledge about such parameters is often missing from the literature, even for well-studied bacteria, such as Bacillus thuringiensis, an endospore-forming insect pathogen, which infects its hosts via the oral route. To characterize bacterial replication success, we made use of an experimental oral infection system for the red flour beetle Tribolium castaneum and developed a flow cytometric assay for the quantification of both spore ingestion by the individual beetle larvae and the resulting spore load after bacterial replication and resporulation within cadavers. On average, spore numbers increased 460-fold, showing that Bacillus thuringiensis grows and replicates successfully in insect cadavers. By inoculating cadaver-derived spores and spores from bacterial stock cultures into nutrient medium, we next investigated outgrowth characteristics of vegetative cells and found that cadaver- derived bacteria showed reduced growth compared to bacteria from the stock cultures. Interestingly, this reduced growth was a consequence of inhibited spore germination, probably originating from the host and resulting in reduced host mortality in subsequent infections by cadaver-derived spores. Nevertheless, we further showed that Bacillus thuringiensis transmission was possible via larval cannibalism when no other food was offered. These results contribute to our understanding of the ecology of Bacillus thuringiensis as an insect pathogen.
AU - Milutinovic, Barbara
AU - Höfling, Christina
AU - Futo, Momir
AU - Scharsack, Jörn
AU - Kurtz, Joachim
ID - 1548
IS - 23
JF - Applied and Environmental Microbiology
TI - Infection of Tribolium castaneum with Bacillus thuringiensis: Quantification of bacterial replication within cadavers, transmission via cannibalism, and inhibition of spore germination
VL - 81
ER -
TY - CHAP
AB - Nature has incorporated small photochromic molecules, colloquially termed 'photoswitches', in photoreceptor proteins to sense optical cues in photo-taxis and vision. While Nature's ability to employ light-responsive functionalities has long been recognized, it was not until recently that scientists designed, synthesized and applied synthetic photochromes to manipulate many of which open rapidly and locally in their native cell types, biological processes with the temporal and spatial resolution of light. Ion channels in particular have come to the forefront of proteins that can be put under the designer control of synthetic photochromes. Photochromic ion channel controllers are comprised of three classes, photochromic soluble ligands (PCLs), photochromic tethered ligands (PTLs) and photochromic crosslinkers (PXs), and in each class ion channel functionality is controlled through reversible changes in photochrome structure. By acting as light-dependent ion channel agonists, antagonist or modulators, photochromic controllers effectively converted a wide range of ion channels, including voltage-gated ion channels, 'leak channels', tri-, tetra- and pentameric ligand-gated ion channels, and temperaturesensitive ion channels, into man-made photoreceptors. Control by photochromes can be reversible, unlike in the case of 'caged' compounds, and non-invasive with high spatial precision, unlike pharmacology and electrical manipulation. Here, we introduce design principles of emerging photochromic molecules that act on ion channels and discuss the impact that these molecules are beginning to have on ion channel biophysics and neuronal physiology.
AU - Mckenzie, Catherine
AU - Sanchez Romero, Inmaculada
AU - Janovjak, Harald L
ID - 1549
SN - 978-1-4939-2844-6
T2 - Novel chemical tools to study ion channel biology
TI - Flipping the photoswitch: Ion channels under light control
VL - 869
ER -
TY - JOUR
AB - The medial ganglionic eminence (MGE) gives rise to the majority of mouse forebrain interneurons. Here, we examine the lineage relationship among MGE-derived interneurons using a replication-defective retroviral library containing a highly diverse set of DNA barcodes. Recovering the barcodes from the mature progeny of infected progenitor cells enabled us to unambiguously determine their respective lineal relationship. We found that clonal dispersion occurs across large areas of the brain and is not restricted by anatomical divisions. As such, sibling interneurons can populate the cortex, hippocampus striatum, and globus pallidus. The majority of interneurons appeared to be generated from asymmetric divisions of MGE progenitor cells, followed by symmetric divisions within the subventricular zone. Altogether, our findings uncover that lineage relationships do not appear to determine interneuron allocation to particular regions. As such, it is likely that clonally related interneurons have considerable flexibility as to the particular forebrain circuits to which they can contribute.
AU - Mayer, Christian
AU - Jaglin, Xavier
AU - Cobbs, Lucy
AU - Bandler, Rachel
AU - Streicher, Carmen
AU - Cepko, Constance
AU - Hippenmeyer, Simon
AU - Fishell, Gord
ID - 1550
IS - 5
JF - Neuron
TI - Clonally related forebrain interneurons disperse broadly across both functional areas and structural boundaries
VL - 87
ER -
TY - JOUR
AB - Reciprocal coevolution between host and pathogen is widely seen as a major driver of evolution and biological innovation. Yet, to date, the underlying genetic mechanisms and associated trait functions that are unique to rapid coevolutionary change are generally unknown. We here combined experimental evolution of the bacterial biocontrol agent Bacillus thuringiensis and its nematode host Caenorhabditis elegans with large-scale phenotyping, whole genome analysis, and functional genetics to demonstrate the selective benefit of pathogen virulence and the underlying toxin genes during the adaptation process. We show that: (i) high virulence was specifically favoured during pathogen–host coevolution rather than pathogen one-sided adaptation to a nonchanging host or to an environment without host; (ii) the pathogen genotype BT-679 with known nematocidal toxin genes and high virulence specifically swept to fixation in all of the independent replicate populations under coevolution but only some under one-sided adaptation; (iii) high virulence in the BT-679-dominated populations correlated with elevated copy numbers of the plasmid containing the nematocidal toxin genes; (iv) loss of virulence in a toxin-plasmid lacking BT-679 isolate was reconstituted by genetic reintroduction or external addition of the toxins.We conclude that sustained coevolution is distinct from unidirectional selection in shaping the pathogen's genome and life history characteristics. To our knowledge, this study is the first to characterize the pathogen genes involved in coevolutionary adaptation in an animal host–pathogen interaction system.
AU - El Masri, Leila
AU - Branca, Antoine
AU - Sheppard, Anna
AU - Papkou, Andrei
AU - Laehnemann, David
AU - Guenther, Patrick
AU - Prahl, Swantje
AU - Saebelfeld, Manja
AU - Hollensteiner, Jacqueline
AU - Liesegang, Heiko
AU - Brzuszkiewicz, Elzbieta
AU - Daniel, Rolf
AU - Michiels, Nico
AU - Schulte, Rebecca
AU - Kurtz, Joachim
AU - Rosenstiel, Philip
AU - Telschow, Arndt
AU - Bornberg Bauer, Erich
AU - Schulenburg, Hinrich
ID - 1551
IS - 6
JF - PLoS Biology
TI - Host–pathogen coevolution: The selective advantage of Bacillus thuringiensis virulence and its cry toxin genes
VL - 13
ER -
TY - JOUR
AB - Cell movement has essential functions in development, immunity, and cancer. Various cell migration patterns have been reported, but no general rule has emerged so far. Here, we show on the basis of experimental data in vitro and in vivo that cell persistence, which quantifies the straightness of trajectories, is robustly coupled to cell migration speed. We suggest that this universal coupling constitutes a generic law of cell migration, which originates in the advection of polarity cues by an actin cytoskeleton undergoing flows at the cellular scale. Our analysis relies on a theoretical model that we validate by measuring the persistence of cells upon modulation of actin flow speeds and upon optogenetic manipulation of the binding of an actin regulator to actin filaments. Beyond the quantitative prediction of the coupling, the model yields a generic phase diagram of cellular trajectories, which recapitulates the full range of observed migration patterns.
AU - Maiuri, Paolo
AU - Rupprecht, Jean
AU - Wieser, Stefan
AU - Ruprecht, Verena
AU - Bénichou, Olivier
AU - Carpi, Nicolas
AU - Coppey, Mathieu
AU - De Beco, Simon
AU - Gov, Nir
AU - Heisenberg, Carl-Philipp J
AU - Lage Crespo, Carolina
AU - Lautenschlaeger, Franziska
AU - Le Berre, Maël
AU - Lennon Duménil, Ana
AU - Raab, Matthew
AU - Thiam, Hawa
AU - Piel, Matthieu
AU - Sixt, Michael K
AU - Voituriez, Raphaël
ID - 1553
IS - 2
JF - Cell
TI - Actin flows mediate a universal coupling between cell speed and cell persistence
VL - 161
ER -
TY - JOUR
AB - The visualization of hormonal signaling input and output is key to understanding how multicellular development is regulated. The plant signaling molecule auxin triggers many growth and developmental responses, but current tools lack the sensitivity or precision to visualize these. We developed a set of fluorescent reporters that allow sensitive and semiquantitative readout of auxin responses at cellular resolution in Arabidopsis thaliana. These generic tools are suitable for any transformable plant species.
AU - Liao, Cheyang
AU - Smet, Wouter
AU - Brunoud, Géraldine
AU - Yoshida, Saiko
AU - Vernoux, Teva
AU - Weijers, Dolf
ID - 1554
IS - 3
JF - Nature Methods
TI - Reporters for sensitive and quantitative measurement of auxin response
VL - 12
ER -
TY - JOUR
AB - We show that incorporating spatial dispersal of individuals into a simple vaccination epidemic model may give rise to a model that exhibits rich dynamical behavior. Using an SIVS (susceptible-infected-vaccinated-susceptible) model as a basis, we describe the spread of an infectious disease in a population split into two regions. In each subpopulation, both forward and backward bifurcations can occur. This implies that for disconnected regions the two-patch system may admit several steady states. We consider traveling between the regions and investigate the impact of spatial dispersal of individuals on the model dynamics. We establish conditions for the existence of multiple nontrivial steady states in the system, and we study the structure of the equilibria. The mathematical analysis reveals an unusually rich dynamical behavior, not normally found in the simple epidemic models. In addition to the disease-free equilibrium, eight endemic equilibria emerge from backward transcritical and saddle-node bifurcation points, forming an interesting bifurcation diagram. Stability of steady states, their bifurcations, and the global dynamics are investigated with analytical tools, numerical simulations, and rigorous set-oriented numerical computations.
AU - Knipl, Diána
AU - Pilarczyk, Pawel
AU - Röst, Gergely
ID - 1555
IS - 2
JF - SIAM Journal on Applied Dynamical Systems
TI - Rich bifurcation structure in a two patch vaccination model
VL - 14
ER -
TY - JOUR
AB - The elongator complex subunit 2 (ELP2) protein, one subunit of an evolutionarily conserved histone acetyltransferase complex, has been shown to participate in leaf patterning, plant immune and abiotic stress responses in Arabidopsis thaliana. Here, its role in root development was explored. Compared to the wild type, the elp2 mutant exhibited an accelerated differentiation of its root stem cells and cell division was more active in its quiescent centre (QC). The key transcription factors responsible for maintaining root stem cell and QC identity, such as AP2 transcription factors PLT1 (PLETHORA1) and PLT2 (PLETHORA2), GRAS transcription factors such as SCR (SCARECROW) and SHR (SHORT ROOT) and WUSCHEL-RELATED HOMEOBOX5 transcription factor WOX5, were all strongly down-regulated in the mutant. On the other hand, expression of the G2/M transition activator CYCB1 was substantially induced in elp2. The auxin efflux transporters PIN1 and PIN2 showed decreased protein levels and PIN1 also displayed mild polarity alterations in elp2, which resulted in a reduced auxin content in the root tip. Either the acetylation or methylation level of each of these genes differed between the mutant and the wild type, suggesting that the ELP2 regulation of root development involves the epigenetic modification of a range of transcription factors and other developmental regulators.
AU - Jia, Yuebin
AU - Tian, Huiyu
AU - Li, Hongjiang
AU - Yu, Qianqian
AU - Wang, Lei
AU - Friml, Jirí
AU - Ding, Zhaojun
ID - 1556
IS - 15
JF - Journal of Experimental Botany
TI - The Arabidopsis thaliana elongator complex subunit 2 epigenetically affects root development
VL - 66
ER -
TY - JOUR
AB - γ-Aminobutyric acid (GABA)- and glycine-mediated hyperpolarizing inhibition is associated with a chloride influx that depends on the inwardly directed chloride electrochemical gradient. In neurons, the extrusion of chloride from the cytosol primarily depends on the expression of an isoform of potassium-chloride cotransporters (KCC2s). KCC2 is crucial in the regulation of the inhibitory tone of neural circuits, including pain processing neural assemblies. Thus we investigated the cellular distribution of KCC2 in neurons underlying pain processing in the superficial spinal dorsal horn of rats by using high-resolution immunocytochemical methods. We demonstrated that perikarya and dendrites widely expressed KCC2, but axon terminals proved to be negative for KCC2. In single ultrathin sections, silver deposits labeling KCC2 molecules showed different densities on the surface of dendritic profiles, some of which were negative for KCC2. In freeze fracture replicas and tissue sections double stained for the β3-subunit of GABAA receptors and KCC2, GABAA receptors were revealed on dendritic segments with high and also with low KCC2 densities. By measuring the distances between spots immunoreactive for gephyrin (a scaffolding protein of GABAA and glycine receptors) and KCC2 on the surface of neurokinin 1 (NK1) receptor-immunoreactive dendrites, we found that gephyrin-immunoreactive spots were located at various distances from KCC2 cotransporters; 5.7 % of them were recovered in the middle of 4-10-μm-long dendritic segments that were free of KCC2 immunostaining. The variable local densities of KCC2 may result in variable postsynaptic potentials evoked by the activation of GABAA and glycine receptors along the dendrites of spinal neurons.
AU - Javdani, Fariba
AU - Holló, Krisztina
AU - Hegedűs, Krisztina
AU - Kis, Gréta
AU - Hegyi, Zoltán
AU - Dócs, Klaudia
AU - Kasugai, Yu
AU - Fukazawa, Yugo
AU - Shigemoto, Ryuichi
AU - Antal, Miklós
ID - 1557
IS - 13
JF - Journal of Comparative Neurology
TI - Differential expression patterns of K+Cl- cotransporter 2 in neurons within the superficial spinal dorsal horn of rats
VL - 523
ER -
TY - JOUR
AB - CyclophilinAis a conserved peptidyl-prolyl cis-trans isomerase (PPIase) best known as the cellular receptor of the immunosuppressant cyclosporine A. Despite significant effort, evidence of developmental functions of cyclophilin A in non-plant systems has remained obscure. Mutations in a tomato (Solanum lycopersicum) cyclophilin A ortholog, DIAGEOTROPICA (DGT), have been shown to abolish the organogenesis of lateral roots; however, a mechanistic explanation of the phenotype is lacking. Here, we show that the dgt mutant lacks auxin maxima relevant to priming and specification of lateral root founder cells. DGT is expressed in shoot and root, and localizes to both the nucleus and cytoplasm during lateral root organogenesis. Mutation of ENTIRE/ IAA9, a member of the auxin-responsive Aux/IAA protein family of transcriptional repressors, partially restores the inability of dgt to initiate lateral root primordia but not the primordia outgrowth. By comparison, grafting of a wild-type scion restores the process of lateral root formation, consistent with participation of a mobile signal. Antibodies do not detect movement of the DGT protein into the dgt rootstock; however, experiments with radiolabeled auxin and an auxin-specific microelectrode demonstrate abnormal auxin fluxes. Functional studies of DGT in heterologous yeast and tobacco-leaf auxin-transport systems demonstrate that DGT negatively regulates PIN-FORMED (PIN) auxin efflux transporters by affecting their plasma membrane localization. Studies in tomato support complex effects of the dgt mutation on PIN expression level, expression domain and plasma membrane localization. Our data demonstrate that DGT regulates auxin transport in lateral root formation.
AU - Ivanchenko, Maria
AU - Zhu, Jinsheng
AU - Wang, Bangjun
AU - Medvecka, Eva
AU - Du, Yunlong
AU - Azzarello, Elisa
AU - Mancuso, Stefano
AU - Megraw, Molly
AU - Filichkin, Sergei
AU - Dubrovsky, Joseph
AU - Friml, Jirí
AU - Geisler, Markus
ID - 1558
IS - 4
JF - Development
TI - The cyclophilin a DIAGEOTROPICA gene affects auxin transport in both root and shoot to control lateral root formation
VL - 142
ER -
TY - JOUR
AB - There are deep, yet largely unexplored, connections between computer science and biology. Both disciplines examine how information proliferates in time and space. Central results in computer science describe the complexity of algorithms that solve certain classes of problems. An algorithm is deemed efficient if it can solve a problem in polynomial time, which means the running time of the algorithm is a polynomial function of the length of the input. There are classes of harder problems for which the fastest possible algorithm requires exponential time. Another criterion is the space requirement of the algorithm. There is a crucial distinction between algorithms that can find a solution, verify a solution, or list several distinct solutions in given time and space. The complexity hierarchy that is generated in this way is the foundation of theoretical computer science. Precise complexity results can be notoriously difficult. The famous question whether polynomial time equals nondeterministic polynomial time (i.e., P = NP) is one of the hardest open problems in computer science and all of mathematics. Here, we consider simple processes of ecological and evolutionary spatial dynamics. The basic question is: What is the probability that a new invader (or a new mutant)will take over a resident population?We derive precise complexity results for a variety of scenarios. We therefore show that some fundamental questions in this area cannot be answered by simple equations (assuming that P is not equal to NP).
AU - Ibsen-Jensen, Rasmus
AU - Chatterjee, Krishnendu
AU - Nowak, Martin
ID - 1559
IS - 51
JF - PNAS
TI - Computational complexity of ecological and evolutionary spatial dynamics
VL - 112
ER -
TY - JOUR
AB - Stromal cells in the subcapsular sinus of the lymph node 'decide' which cells and molecules are allowed access to the deeper parenchyma. The glycoprotein PLVAP is a crucial component of this selector function.
AU - Hons, Miroslav
AU - Sixt, Michael K
ID - 1560
IS - 4
JF - Nature Immunology
TI - The lymph node filter revealed
VL - 16
ER -
TY - JOUR
AB - Replication-deficient recombinant adenoviruses are potent vectors for the efficient transient expression of exogenous genes in resting immune cells. However, most leukocytes are refractory to efficient adenoviral transduction as they lack expression of the coxsackie/adenovirus receptor (CAR). To circumvent this obstacle, we generated the R26/CAG-CARΔ1StopF (where R26 is ROSA26 and CAG is CMV early enhancer/chicken β actin promoter) knock-in mouse line. This strain allows monitoring of in situ Cre recombinase activity through expression of CARΔ1. Simultaneously, CARΔ1 expression permits selective and highly efficient adenoviral transduction of immune cell populations, such as mast cells or T cells, directly ex vivo in bulk cultures without prior cell purification or activation. Furthermore, we show that CARΔ1 expression dramatically improves adenoviral infection of in vitro differentiated conventional and plasmacytoid dendritic cells (DCs), basophils, mast cells, as well as Hoxb8-immortalized hematopoietic progenitor cells. This novel dual function mouse strain will hence be a valuable tool to rapidly dissect the function of specific genes in leukocyte physiology.
AU - Heger, Klaus
AU - Kober, Maike
AU - Rieß, David
AU - Drees, Christoph
AU - De Vries, Ingrid
AU - Bertossi, Arianna
AU - Roers, Axel
AU - Sixt, Michael K
AU - Schmidt Supprian, Marc
ID - 1561
IS - 6
JF - European Journal of Immunology
TI - A novel Cre recombinase reporter mouse strain facilitates selective and efficient infection of primary immune cells with adenoviral vectors
VL - 45
ER -
TY - JOUR
AB - The plant hormone auxin is a key regulator of plant growth and development. Auxin levels are sensed and interpreted by distinct receptor systems that activate a broad range of cellular responses. The Auxin-Binding Protein1 (ABP1) that has been identified based on its ability to bind auxin with high affinity is a prime candidate for the extracellular receptor responsible for mediating a range of auxin effects, in particular, the fast non-transcriptional ones. Contradictory genetic studies suggested prominent or no importance of ABP1 in many developmental processes. However, how crucial the role of auxin binding to ABP1 is for its functions has not been addressed. Here, we show that the auxin-binding pocket of ABP1 is essential for its gain-of-function cellular and developmental roles. In total, 16 different abp1 mutants were prepared that possessed substitutions in the metal core or in the hydrophobic amino acids of the auxin-binding pocket as well as neutral mutations. Their analysis revealed that an intact auxin-binding pocket is a prerequisite for ABP1 to activate downstream components of the ABP1 signalling pathway, such as Rho of Plants (ROPs) and to mediate the clathrin association with membranes for endocytosis regulation. In planta analyses demonstrated the importance of the auxin binding pocket for all known ABP1-mediated postembryonic developmental processes, including morphology of leaf epidermal cells, root growth and root meristem activity, and vascular tissue differentiation. Taken together, these findings suggest that auxin binding to ABP1 is central to its function, supporting the role of ABP1 as auxin receptor.
AU - Grones, Peter
AU - Chen, Xu
AU - Simon, Sibu
AU - Kaufmann, Walter
AU - De Rycke, Riet
AU - Nodzyński, Tomasz
AU - Zažímalová, Eva
AU - Friml, Jirí
ID - 1562
IS - 16
JF - Journal of Experimental Botany
TI - Auxin-binding pocket of ABP1 is crucial for its gain-of-function cellular and developmental roles
VL - 66
ER -
TY - JOUR
AB - For a given self-map $f$ of $M$, a closed smooth connected and simply-connected manifold of dimension $m\geq 4$, we provide an algorithm for estimating the values of the topological invariant $D^m_r[f]$, which equals the minimal number of $r$-periodic points in the smooth homotopy class of $f$. Our results are based on the combinatorial scheme for computing $D^m_r[f]$ introduced by G. Graff and J. Jezierski [J. Fixed Point Theory Appl. 13 (2013), 63-84]. An open-source implementation of the algorithm programmed in C++ is publicly available at {\tt http://www.pawelpilarczyk.com/combtop/}.
AU - Graff, Grzegorz
AU - Pilarczyk, Pawel
ID - 1563
IS - 1
JF - Topological Methods in Nonlinear Analysis
TI - An algorithmic approach to estimating the minimal number of periodic points for smooth self-maps of simply-connected manifolds
VL - 45
ER -
TY - JOUR
AU - Gilson, Matthieu
AU - Savin, Cristina
AU - Zenke, Friedemann
ID - 1564
IS - 11
JF - Frontiers in Computational Neuroscience
TI - Editorial: Emergent neural computation from the interaction of different forms of plasticity
VL - 9
ER -
TY - JOUR
AB - Leptin is an adipokine produced by the adipose tissue regulating body weight through its appetite-suppressing effect. Besides being expressed in the hypothalamus and hippocampus, leptin receptors (ObRs) are also present in chromaffin cells of the adrenal medulla. In the present study, we report the effect of leptin on mouse chromaffin cell (MCC) functionality, focusing on cell excitability and catecholamine secretion. Acute application of leptin (1 nm) on spontaneously firing MCCs caused a slowly developing membrane hyperpolarization followed by complete blockade of action potential (AP) firing. This inhibitory effect at rest was abolished by the BK channel blocker paxilline (1 μm), suggesting the involvement of BK potassium channels. Single-channel recordings in 'perforated microvesicles' confirmed that leptin increased BK channel open probability without altering its unitary conductance. BK channel up-regulation was associated with the phosphoinositide 3-kinase (PI3K) signalling cascade because the PI3K specific inhibitor wortmannin (100 nm) fully prevented BK current increase. We also tested the effect of leptin on evoked AP firing and Ca2+-driven exocytosis. Although leptin preserves well-adapted AP trains of lower frequency, APs are broader and depolarization-evoked exocytosis is increased as a result of the larger size of the ready-releasable pool and higher frequency of vesicle release. The kinetics and quantal size of single secretory events remained unaltered. Leptin had no effect on firing and secretion in db-/db- mice lacking the ObR gene, confirming its specificity. In conclusion, leptin exhibits a dual action on MCC activity. It dampens AP firing at rest but preserves AP firing and increases catecholamine secretion during sustained stimulation, highlighting the importance of the adipo-adrenal axis in the leptin-mediated increase of sympathetic tone and catecholamine release.
AU - Gavello, Daniela
AU - Vandael, David H
AU - Gosso, Sara
AU - Carbone, Emilio
AU - Carabelli, Valentina
ID - 1565
IS - 22
JF - Journal of Physiology
TI - Dual action of leptin on rest-firing and stimulated catecholamine release via phosphoinositide 3-kinase-riven BK channel up-regulation in mouse chromaffin cells
VL - 593
ER -
TY - JOUR
AB - Deposits of misfolded proteins in the human brain are associated with the development of many neurodegenerative diseases. Recent studies show that these proteins have common traits even at the monomer level. Among them, a polyglutamine region that is present in huntingtin is known to exhibit a correlation between the length of the chain and the severity as well as the earliness of the onset of Huntington disease. Here, we apply bias exchange molecular dynamics to generate structures of polyglutamine expansions of several lengths and characterize the resulting independent conformations. We compare the properties of these conformations to those of the standard proteins, as well as to other homopolymeric tracts. We find that, similar to the previously studied polyvaline chains, the set of possible transient folds is much broader than the set of known-to-date folds, although the conformations have different structures. We show that the mechanical stability is not related to any simple geometrical characteristics of the structures. We demonstrate that long polyglutamine expansions result in higher mechanical stability than the shorter ones. They also have a longer life span and are substantially more prone to form knotted structures. The knotted region has an average length of 35 residues, similar to the typical threshold for most polyglutamine-related diseases. Similarly, changes in shape and mechanical stability appear once the total length of the peptide exceeds this threshold of 35 glutamine residues. We suggest that knotted conformers may also harm the cellular machinery and thus lead to disease.
AU - Gómez Sicilia, Àngel
AU - Sikora, Mateusz K
AU - Cieplak, Marek
AU - Carrión Vázquez, Mariano
ID - 1566
IS - 10
JF - PLoS Computational Biology
TI - An exploration of the universe of polyglutamine structures
VL - 11
ER -
TY - CONF
AB - My personal journey to the fascinating world of geometric forms started more than 30 years ago with the invention of alpha shapes in the plane. It took about 10 years before we generalized the concept to higher dimensions, we produced working software with a graphics interface for the three-dimensional case. At the same time, we added homology to the computations. Needless to say that this foreshadowed the inception of persistent homology, because it suggested the study of filtrations to capture the scale of a shape or data set. Importantly, this method has fast algorithms. The arguably most useful result on persistent homology is the stability of its diagrams under perturbations.
AU - Edelsbrunner, Herbert
ID - 1567
T2 - 23rd International Symposium
TI - Shape, homology, persistence, and stability
VL - 9411
ER -
TY - CONF
AB - Aiming at the automatic diagnosis of tumors from narrow band imaging (NBI) magnifying endoscopy (ME) images of the stomach, we combine methods from image processing, computational topology, and machine learning to classify patterns into normal, tubular, vessel. Training the algorithm on a small number of images of each type, we achieve a high rate of correct classifications. The analysis of the learning algorithm reveals that a handful of geometric and topological features are responsible for the overwhelming majority of decisions.
AU - Dunaeva, Olga
AU - Edelsbrunner, Herbert
AU - Lukyanov, Anton
AU - Machin, Michael
AU - Malkova, Daria
ID - 1568
T2 - Proceedings - 16th International Symposium on Symbolic and Numeric Algorithms for Scientific Computing
TI - The classification of endoscopy images with persistent homology
ER -
TY - JOUR
AB - Spatial regulation of the plant hormone indole-3-acetic acid (IAA, or auxin) is essential for plant development. Auxin gradient establishment is mediated by polarly localized auxin transporters, including PIN-FORMED (PIN) proteins. Their localization and abundance at the plasma membrane are tightly regulated by endomembrane machinery, especially the endocytic and recycling pathways mediated by the ADP ribosylation factor guanine nucleotide exchange factor (ARF-GEF) GNOM. We assessed the role of the early secretory pathway in establishing PIN1 polarity in Arabidopsis thaliana by pharmacological and genetic approaches. We identified the compound endosidin 8 (ES8), which selectively interferes with PIN1 basal polarity without altering the polarity of apical proteins. ES8 alters the auxin distribution pattern in the root and induces a strong developmental phenotype, including reduced root length. The ARF-GEF- defective mutants gnom-like 1 ( gnl1-1) and gnom ( van7) are significantly resistant to ES8. The compound does not affect recycling or vacuolar trafficking of PIN1 but leads to its intracellular accumulation, resulting in loss of PIN1 basal polarity at the plasma membrane. Our data confirm a role for GNOM in endoplasmic reticulum (ER) - Golgi trafficking and reveal that a GNL1/GNOM-mediated early secretory pathway selectively regulates PIN1 basal polarity establishment in a manner essential for normal plant development.
AU - Doyle, Siamsa
AU - Haegera, Ash
AU - Vain, Thomas
AU - Rigala, Adeline
AU - Viotti, Corrado
AU - Łangowskaa, Małgorzata
AU - Maa, Qian
AU - Friml, Jirí
AU - Raikhel, Natasha
AU - Hickse, Glenn
AU - Robert, Stéphanie
ID - 1569
IS - 7
JF - PNAS
TI - An early secretory pathway mediated by gnom-like 1 and gnom is essential for basal polarity establishment in Arabidopsis thaliana
VL - 112
ER -
TY - JOUR
AB - Grounding autonomous behavior in the nervous system is a fundamental challenge for neuroscience. In particular, self-organized behavioral development provides more questions than answers. Are there special functional units for curiosity, motivation, and creativity? This paper argues that these features can be grounded in synaptic plasticity itself, without requiring any higher-level constructs. We propose differential extrinsic plasticity (DEP) as a new synaptic rule for self-learning systems and apply it to a number of complex robotic systems as a test case. Without specifying any purpose or goal, seemingly purposeful and adaptive rhythmic behavior is developed, displaying a certain level of sensorimotor intelligence. These surprising results require no systemspecific modifications of the DEP rule. They rather arise from the underlying mechanism of spontaneous symmetry breaking,which is due to the tight brain body environment coupling. The new synaptic rule is biologically plausible and would be an interesting target for neurobiological investigation. We also argue that this neuronal mechanism may have been a catalyst in natural evolution.
AU - Der, Ralf
AU - Martius, Georg S
ID - 1570
IS - 45
JF - PNAS
TI - Novel plasticity rule can explain the development of sensorimotor intelligence
VL - 112
ER -
TY - JOUR
AB - Epistatic interactions can frustrate and shape evolutionary change. Indeed, phenotypes may fail to evolve when essential mutations are only accessible through positive selection if they are fixed simultaneously. How environmental variability affects such constraints is poorly understood. Here, we studied genetic constraints in fixed and fluctuating environments using the Escherichia coli lac operon as a model system for genotype-environment interactions. We found that, in different fixed environments, all trajectories that were reconstructed by applying point mutations within the transcription factor-operator interface became trapped at suboptima, where no additional improvements were possible. Paradoxically, repeated switching between these same environments allows unconstrained adaptation by continuous improvements. This evolutionary mode is explained by pervasive cross-environmental tradeoffs that reposition the peaks in such a way that trapped genotypes can repeatedly climb ascending slopes and hence, escape adaptive stasis. Using a Markov approach, we developed a mathematical framework to quantify the landscape-crossing rates and show that this ratchet-like adaptive mechanism is robust in a wide spectrum of fluctuating environments. Overall, this study shows that genetic constraints can be overcome by environmental change and that crossenvironmental tradeoffs do not necessarily impede but also, can facilitate adaptive evolution. Because tradeoffs and environmental variability are ubiquitous in nature, we speculate this evolutionary mode to be of general relevance.
AU - De Vos, Marjon
AU - Dawid, Alexandre
AU - Šunderlíková, Vanda
AU - Tans, Sander
ID - 1571
IS - 48
JF - PNAS
TI - Breaking evolutionary constraint with a tradeoff ratchet
VL - 112
ER -
TY - JOUR
AB - We consider the quantum ferromagnetic Heisenberg model in three dimensions, for all spins S ≥ 1/2. We rigorously prove the validity of the spin-wave approximation for the excitation spectrum, at the level of the first non-trivial contribution to the free energy at low temperatures. Our proof comes with explicit, constructive upper and lower bounds on the error term. It uses in an essential way the bosonic formulation of the model in terms of the Holstein-Primakoff representation. In this language, the model describes interacting bosons with a hard-core on-site repulsion and a nearest-neighbor attraction. This attractive interaction makes the lower bound on the free energy particularly tricky: the key idea there is to prove a differential inequality for the two-particle density, which is thereby shown to be smaller than the probability density of a suitably weighted two-particle random process on the lattice.
AU - Correggi, Michele
AU - Giuliani, Alessandro
AU - Seiringer, Robert
ID - 1572
IS - 1
JF - Communications in Mathematical Physics
TI - Validity of the spin-wave approximation for the free energy of the Heisenberg ferromagnet
VL - 339
ER -
TY - JOUR
AB - We present a new, simpler proof of the unconditional uniqueness of solutions to the cubic Gross-Pitaevskii hierarchy in ℝ3. One of the main tools in our analysis is the quantum de Finetti theorem. Our uniqueness result is equivalent to the one established in the celebrated works of Erdos, Schlein, and Yau.
AU - Chen, Thomas
AU - Hainzl, Christian
AU - Pavlović, Nataša
AU - Seiringer, Robert
ID - 1573
IS - 10
JF - Communications on Pure and Applied Mathematics
TI - Unconditional uniqueness for the cubic gross pitaevskii hierarchy via quantum de finetti
VL - 68
ER -
TY - JOUR
AB - Multiple plant developmental processes, such as lateral root development, depend on auxin distribution patterns that are in part generated by the PIN-formed family of auxin-efflux transporters. Here we propose that AUXIN RESPONSE FACTOR7 (ARF7) and the ARF7-regulated FOUR LIPS/MYB124 (FLP) transcription factors jointly form a coherent feed-forward motif that mediates the auxin-responsive PIN3 transcription in planta to steer the early steps of lateral root formation. This regulatory mechanism might endow the PIN3 circuitry with a temporal 'memory' of auxin stimuli, potentially maintaining and enhancing the robustness of the auxin flux directionality during lateral root development. The cooperative action between canonical auxin signalling and other transcription factors might constitute a general mechanism by which transcriptional auxin-sensitivity can be regulated at a tissue-specific level.
AU - Chen, Qian
AU - Liu, Yang
AU - Maere, Steven
AU - Lee, Eunkyoung
AU - Van Isterdael, Gert
AU - Xie, Zidian
AU - Xuan, Wei
AU - Lucas, Jessica
AU - Vassileva, Valya
AU - Kitakura, Saeko
AU - Marhavy, Peter
AU - Wabnik, Krzysztof T
AU - Geldner, Niko
AU - Benková, Eva
AU - Le, Jie
AU - Fukaki, Hidehiro
AU - Grotewold, Erich
AU - Li, Chuanyou
AU - Friml, Jirí
AU - Sack, Fred
AU - Beeckman, Tom
AU - Vanneste, Steffen
ID - 1574
JF - Nature Communications
TI - A coherent transcriptional feed-forward motif model for mediating auxin-sensitive PIN3 expression during lateral root development
VL - 6
ER -
TY - JOUR
AB - The immune response relies on the migration of leukocytes and on their ability to stop in precise anatomical locations to fulfil their task. How leukocyte migration and function are coordinated is unknown. Here we show that in immature dendritic cells, which patrol their environment by engulfing extracellular material, cell migration and antigen capture are antagonistic. This antagonism results from transient enrichment of myosin IIA at the cell front, which disrupts the back-to-front gradient of the motor protein, slowing down locomotion but promoting antigen capture. We further highlight that myosin IIA enrichment at the cell front requires the MHC class II-associated invariant chain (Ii). Thus, by controlling myosin IIA localization, Ii imposes on dendritic cells an intermittent antigen capture behaviour that might facilitate environment patrolling. We propose that the requirement for myosin II in both cell migration and specific cell functions may provide a general mechanism for their coordination in time and space.
AU - Chabaud, Mélanie
AU - Heuzé, Mélina
AU - Bretou, Marine
AU - Vargas, Pablo
AU - Maiuri, Paolo
AU - Solanes, Paola
AU - Maurin, Mathieu
AU - Terriac, Emmanuel
AU - Le Berre, Maël
AU - Lankar, Danielle
AU - Piolot, Tristan
AU - Adelstein, Robert
AU - Zhang, Yingfan
AU - Sixt, Michael K
AU - Jacobelli, Jordan
AU - Bénichou, Olivier
AU - Voituriez, Raphaël
AU - Piel, Matthieu
AU - Lennon Duménil, Ana
ID - 1575
JF - Nature Communications
TI - Cell migration and antigen capture are antagonistic processes coupled by myosin II in dendritic cells
VL - 6
ER -
TY - JOUR
AB - Gene expression is controlled primarily by interactions between transcription factor proteins (TFs) and the regulatory DNA sequence, a process that can be captured well by thermodynamic models of regulation. These models, however, neglect regulatory crosstalk: the possibility that noncognate TFs could initiate transcription, with potentially disastrous effects for the cell. Here, we estimate the importance of crosstalk, suggest that its avoidance strongly constrains equilibrium models of TF binding, and propose an alternative nonequilibrium scheme that implements kinetic proofreading to suppress erroneous initiation. This proposal is consistent with the observed covalent modifications of the transcriptional apparatus and predicts increased noise in gene expression as a trade-off for improved specificity. Using information theory, we quantify this trade-off to find when optimal proofreading architectures are favored over their equilibrium counterparts. Such architectures exhibit significant super-Poisson noise at low expression in steady state.
AU - Cepeda Humerez, Sarah A
AU - Rieckh, Georg
AU - Tkacik, Gasper
ID - 1576
IS - 24
JF - Physical Review Letters
TI - Stochastic proofreading mechanism alleviates crosstalk in transcriptional regulation
VL - 115
ER -
TY - JOUR
AB - Contrary to the pattern seen in mammalian sex chromosomes, where most Y-linked genes have X-linked homologs, the Drosophila X and Y chromosomes appear to be unrelated. Most of the Y-linked genes have autosomal paralogs, so autosome-to-Y transposition must be the main source of Drosophila Y-linked genes. Here we show how these genes were acquired. We found a previously unidentified gene (flagrante delicto Y, FDY) that originated from a recent duplication of the autosomal gene vig2 to the Y chromosome of Drosophila melanogaster. Four contiguous genes were duplicated along with vig2, but they became pseudogenes through the accumulation of deletions and transposable element insertions, whereas FDY remained functional, acquired testis-specific expression, and now accounts for ∼20% of the vig2-like mRNA in testis. FDY is absent in the closest relatives of D. melanogaster, and DNA sequence divergence indicates that the duplication to the Y chromosome occurred ∼2 million years ago. Thus, FDY provides a snapshot of the early stages of the establishment of a Y-linked gene and demonstrates how the Drosophila Y has been accumulating autosomal genes.
AU - Carvalho, Antonio
AU - Vicoso, Beatriz
AU - Russo, Claudia
AU - Swenor, Bonnielin
AU - Clark, Andrew
ID - 1577
IS - 40
JF - PNAS
TI - Birth of a new gene on the Y chromosome of Drosophila melanogaster
VL - 112
ER -
TY - JOUR
AB - We prove that the dual of the digital Voronoi diagram constructed by flooding the plane from the data points gives a geometrically and topologically correct dual triangulation. This provides the proof of correctness for recently developed GPU algorithms that outperform traditional CPU algorithms for constructing two-dimensional Delaunay triangulations.
AU - Cao, Thanhtung
AU - Edelsbrunner, Herbert
AU - Tan, Tiowseng
ID - 1578
IS - 7
JF - Computational Geometry
TI - Triangulations from topologically correct digital Voronoi diagrams
VL - 48
ER -
TY - JOUR
AB - We show that the Galois group of any Schubert problem involving lines in projective space contains the alternating group. This constitutes the largest family of enumerative problems whose Galois groups have been largely determined. Using a criterion of Vakil and a special position argument due to Schubert, our result follows from a particular inequality among Kostka numbers of two-rowed tableaux. In most cases, a combinatorial injection proves the inequality. For the remaining cases, we use the Weyl integral formulas to obtain an integral formula for these Kostka numbers. This rewrites the inequality as an integral, which we estimate to establish the inequality.
AU - Brooks, Christopher
AU - Martin Del Campo Sanchez, Abraham
AU - Sottile, Frank
ID - 1579
IS - 6
JF - Transactions of the American Mathematical Society
TI - Galois groups of Schubert problems of lines are at least alternating
VL - 367
ER -
TY - JOUR
AB - Synapsins (Syns) are an evolutionarily conserved family of presynaptic proteins crucial for the fine-tuning of synaptic function. A large amount of experimental evidences has shown that Syns are involved in the development of epileptic phenotypes and several mutations in Syn genes have been associated with epilepsy in humans and animal models. Syn mutations induce alterations in circuitry and neurotransmitter release, differentially affecting excitatory and inhibitory synapses, thus causing an excitation/inhibition imbalance in network excitability toward hyperexcitability that may be a determinant with regard to the development of epilepsy. Another approach to investigate epileptogenic mechanisms is to understand how silencing Syn affects the cellular behavior of single neurons and is associated with the hyperexcitable phenotypes observed in epilepsy. Here, we examined the functional effects of antisense-RNA inhibition of Syn expression on individually identified and isolated serotonergic cells of the Helix land snail. We found that Helix synapsin silencing increases cell excitability characterized by a slightly depolarized resting membrane potential, decreases the rheobase, reduces the threshold for action potential (AP) firing and increases the mean and instantaneous firing rates, with respect to control cells. The observed increase of Ca2+ and BK currents in Syn-silenced cells seems to be related to changes in the shape of the AP waveform. These currents sustain the faster spiking in Syn-deficient cells by increasing the after hyperpolarization and limiting the Na+ and Ca2+ channel inactivation during repetitive firing. This in turn speeds up the depolarization phase by reaching the AP threshold faster. Our results provide evidence that Syn silencing increases intrinsic cell excitability associated with increased Ca2+ and Ca2+-dependent BK currents in the absence of excitatory or inhibitory inputs.
AU - Brenes, Oscar
AU - Vandael, David H
AU - Carbone, Emilio
AU - Montarolo, Pier
AU - Ghirardi, Mirella
ID - 1580
JF - Neuroscience
TI - Knock-down of synapsin alters cell excitability and action potential waveform by potentiating BK and voltage gated Ca2 currents in Helix serotonergic neurons
VL - 311
ER -
TY - JOUR
AB - In animal embryos, morphogen gradients determine tissue patterning and morphogenesis. Shyer et al. provide evidence that, during vertebrate gut formation, tissue folding generates graded activity of signals required for subsequent steps of gut growth and differentiation, thereby revealing an intriguing link between tissue morphogenesis and morphogen gradient formation.
AU - Bollenbach, Mark Tobias
AU - Heisenberg, Carl-Philipp J
ID - 1581
IS - 3
JF - Cell
TI - Gradients are shaping up
VL - 161
ER -
TY - JOUR
AB - We investigate weighted straight skeletons from a geometric, graph-theoretical, and combinatorial point of view. We start with a thorough definition and shed light on some ambiguity issues in the procedural definition. We investigate the geometry, combinatorics, and topology of faces and the roof model, and we discuss in which cases a weighted straight skeleton is connected. Finally, we show that the weighted straight skeleton of even a simple polygon may be non-planar and may contain cycles, and we discuss under which restrictions on the weights and/or the input polygon the weighted straight skeleton still behaves similar to its unweighted counterpart. In particular, we obtain a non-procedural description and a linear-time construction algorithm for the straight skeleton of strictly convex polygons with arbitrary weights.
AU - Biedl, Therese
AU - Held, Martin
AU - Huber, Stefan
AU - Kaaser, Dominik
AU - Palfrader, Peter
ID - 1582
IS - 2
JF - Computational Geometry: Theory and Applications
TI - Weighted straight skeletons in the plane
VL - 48
ER -
TY - JOUR
AB - We study the characteristics of straight skeletons of monotone polygonal chains and use them to devise an algorithm for computing positively weighted straight skeletons of monotone polygons. Our algorithm runs in O(nlogn) time and O(n) space, where n denotes the number of vertices of the polygon.
AU - Biedl, Therese
AU - Held, Martin
AU - Huber, Stefan
AU - Kaaser, Dominik
AU - Palfrader, Peter
ID - 1583
IS - 2
JF - Information Processing Letters
TI - A simple algorithm for computing positively weighted straight skeletons of monotone polygons
VL - 115
ER -
TY - JOUR
AB - We investigate weighted straight skeletons from a geometric, graph-theoretical, and combinatorial point of view. We start with a thorough definition and shed light on some ambiguity issues in the procedural definition. We investigate the geometry, combinatorics, and topology of faces and the roof model, and we discuss in which cases a weighted straight skeleton is connected. Finally, we show that the weighted straight skeleton of even a simple polygon may be non-planar and may contain cycles, and we discuss under which restrictions on the weights and/or the input polygon the weighted straight skeleton still behaves similar to its unweighted counterpart. In particular, we obtain a non-procedural description and a linear-time construction algorithm for the straight skeleton of strictly convex polygons with arbitrary weights.
AU - Biedl, Therese
AU - Held, Martin
AU - Huber, Stefan
AU - Kaaser, Dominik
AU - Palfrader, Peter
ID - 1584
IS - 5
JF - Computational Geometry: Theory and Applications
TI - Reprint of: Weighted straight skeletons in the plane
VL - 48
ER -
TY - JOUR
AB - In this paper, we consider the fluctuation of mutual information statistics of a multiple input multiple output channel communication systems without assuming that the entries of the channel matrix have zero pseudovariance. To this end, we also establish a central limit theorem of the linear spectral statistics for sample covariance matrices under general moment conditions by removing the restrictions imposed on the second moment and fourth moment on the matrix entries in Bai and Silverstein (2004).
AU - Bao, Zhigang
AU - Pan, Guangming
AU - Zhou, Wang
ID - 1585
IS - 6
JF - IEEE Transactions on Information Theory
TI - Asymptotic mutual information statistics of MIMO channels and CLT of sample covariance matrices
VL - 61
ER -
TY - JOUR
AB - Through metabolic engineering cyanobacteria can be employed in biotechnology. Combining the capacity for oxygenic photosynthesis and carbon fixation with an engineered metabolic pathway allows carbon-based product formation from CO2, light, and water directly. Such cyanobacterial 'cell factories' are constructed to produce biofuels, bioplastics, and commodity chemicals. Efforts of metabolic engineers and synthetic biologists allow the modification of the intermediary metabolism at various branching points, expanding the product range. The new biosynthesis routes 'tap' the metabolism ever more efficiently, particularly through the engineering of driving forces and utilization of cofactors generated during the light reactions of photosynthesis, resulting in higher product titers. High rates of carbon rechanneling ultimately allow an almost-complete allocation of fixed carbon to product above biomass.
AU - Angermayr, Andreas
AU - Gorchs, Aleix
AU - Hellingwerf, Klaas
ID - 1586
IS - 6
JF - Trends in Biotechnology
TI - Metabolic engineering of cyanobacteria for the synthesis of commodity products
VL - 33
ER -
TY - JOUR
AB - We investigate the quantum interference shifts between energetically close states, where the state structure is observed by laser spectroscopy. We report a compact and analytical expression that models the quantum interference induced shift for any admixture of circular polarization of the incident laser and angle of observation. An experimental scenario free of quantum interference can thus be predicted with this formula. Although this study is exemplified here for muonic deuterium, it can be applied to any other laser spectroscopy measurement of ns-n′p frequencies of a nonrelativistic atomic system, via an ns→n′p→n′′s scheme.
AU - Amaro, Pedro
AU - Fratini, Filippo
AU - Safari, Laleh
AU - Antognini, Aldo
AU - Indelicato, Paul
AU - Pohl, Randolf
AU - Santos, José
ID - 1587
IS - 6
JF - Physical Review A - Atomic, Molecular, and Optical Physics
TI - Quantum interference shifts in laser spectroscopy with elliptical polarization
VL - 92
ER -
TY - JOUR
AB - We investigate the Taylor-Couette system where the radius ratio is close to unity. Systematically increasing the Reynolds number, we observe a number of previously known transitions, such as one from the classical Taylor vortex flow (TVF) to wavy vortex flow (WVF) and the transition to fully developed turbulence. Prior to the onset of turbulence, we observe intermittent bursting patterns of localized turbulent patches, confirming the experimentally observed pattern of very short wavelength bursts (VSWBs). A striking finding is that, for a Reynolds number larger than that for the onset of VSWBs, a new type of intermittently bursting behavior emerges: patterns of azimuthally closed rings of various orders. We call them ring-bursting patterns, which surround the cylinder completely but remain localized and separated in the axial direction through nonturbulent wavy structures. We employ a number of quantitative measures including the cross-flow energy to characterize the ring-bursting patterns and to distinguish them from the background flow. These patterns are interesting because they do not occur in the wide-gap Taylor-Couette flow systems. The narrow-gap regime is less studied but certainly deserves further attention to gain deeper insights into complex flow dynamics in fluids.
AU - Altmeyer, Sebastian
AU - Do, Younghae
AU - Lai, Ying
ID - 1588
IS - 5
JF - Physical Review E
TI - Ring-bursting behavior en route to turbulence in narrow-gap Taylor-Couette flows
VL - 92
ER -
TY - JOUR
AB - We investigate the dynamics of ferrofluidic wavy vortex flows in the counter-rotating Taylor-Couette system, with a focus on wavy flows with a mixture of the dominant azimuthal modes. Without external magnetic field flows are stable and pro-grade with respect to the rotation of the inner cylinder. More complex behaviors can arise when an axial or a transverse magnetic field is applied. Depending on the direction and strength of the field, multi-stable wavy states and bifurcations can occur. We uncover the phenomenon of flow pattern reversal as the strength of the magnetic field is increased through a critical value. In between the regimes of pro-grade and retrograde flow rotations, standing waves with zero angular velocities can emerge. A striking finding is that, under a transverse magnetic field, a second reversal in the flow pattern direction can occur, where the flow pattern evolves into pro-grade rotation again from a retrograde state. Flow reversal is relevant to intriguing phenomena in nature such as geomagnetic reversal. Our results suggest that, in ferrofluids, flow pattern reversal can be induced by varying a magnetic field in a controlled manner, which can be realized in laboratory experiments with potential applications in the development of modern fluid devices.
AU - Altmeyer, Sebastian
AU - Do, Younghae
AU - Lai, Ying
ID - 1589
JF - Scientific Reports
TI - Magnetic field induced flow pattern reversal in a ferrofluidic Taylor-Couette system
VL - 5
ER -
TY - CHAP
AB - The straight skeleton of a polygon is the geometric graph obtained by tracing the vertices during a mitered offsetting process. It is known that the straight skeleton of a simple polygon is a tree, and one can naturally derive directions on the edges of the tree from the propagation of the shrinking process. In this paper, we ask the reverse question: Given a tree with directed edges, can it be the straight skeleton of a polygon? And if so, can we find a suitable simple polygon? We answer these questions for all directed trees where the order of edges around each node is fixed.
AU - Aichholzer, Oswin
AU - Biedl, Therese
AU - Hackl, Thomas
AU - Held, Martin
AU - Huber, Stefan
AU - Palfrader, Peter
AU - Vogtenhuber, Birgit
ID - 1590
SN - 978-3-319-27260-3
T2 - Graph Drawing and Network Visualization
TI - Representing directed trees as straight skeletons
VL - 9411
ER -
TY - JOUR
AB - Auxin participates in a multitude of developmental processes, as well as responses to environmental cues. Compared with other plant hormones, auxin exhibits a unique property, as it undergoes directional, cell-to-cell transport facilitated by plasma membrane-localized transport proteins. Among them, a prominent role has been ascribed to the PIN family of auxin efflux facilitators. PIN proteins direct polar auxin transport on account of their asymmetric subcellular localizations. In this review, we provide an overview of the multiple developmental roles of PIN proteins, including the atypical endoplasmic reticulum-localized members of the family, and look at the family from an evolutionary perspective. Next, we cover the cell biological and molecular aspects of PIN function, in particular the establishment of their polar subcellular localization. Hormonal and environmental inputs into the regulation of PIN action are summarized as well.
AU - Adamowski, Maciek
AU - Friml, Jirí
ID - 1591
IS - 1
JF - Plant Cell
TI - PIN-dependent auxin transport: Action, regulation, and evolution
VL - 27
ER -
TY - JOUR
AB - Plants are sessile organisms that are permanently restricted to their site of germination. To compensate for their lack of mobility, plants evolved unique mechanisms enabling them to rapidly react to ever changing environmental conditions and flexibly adapt their postembryonic developmental program. A prominent demonstration of this developmental plasticity is their ability to bend organs in order to reach the position most optimal for growth and utilization of light, nutrients, and other resources. Shortly after germination, dicotyledonous seedlings form a bended structure, the so-called apical hook, to protect the delicate shoot meristem and cotyledons from damage when penetrating through the soil. Upon perception of a light stimulus, the apical hook rapidly opens and the photomorphogenic developmental program is activated. After germination, plant organs are able to align their growth with the light source and adopt the most favorable orientation through bending, in a process named phototropism. On the other hand, when roots and shoots are diverted from their upright orientation, they immediately detect a change in the gravity vector and bend to maintain a vertical growth direction. Noteworthy, despite the diversity of external stimuli perceived by different plant organs, all plant tropic movements share a common mechanistic basis: differential cell growth. In our review, we will discuss the molecular principles underlying various tropic responses with the focus on mechanisms mediating the perception of external signals, transduction cascades and downstream responses that regulate differential cell growth and consequently, organ bending. In particular, we highlight common and specific features of regulatory pathways in control of the bending of organs and a role for the plant hormone auxin as a key regulatory component.
AU - Žádníková, Petra
AU - Smet, Dajo
AU - Zhu, Qiang
AU - Van Der Straeten, Dominique
AU - Benková, Eva
ID - 1593
IS - 4
JF - Frontiers in Plant Science
TI - Strategies of seedlings to overcome their sessile nature: Auxin in mobility control
VL - 6
ER -
TY - CONF
AB - Quantitative extensions of temporal logics have recently attracted significant attention. In this work, we study frequency LTL (fLTL), an extension of LTL which allows to speak about frequencies of events along an execution. Such an extension is particularly useful for probabilistic systems that often cannot fulfil strict qualitative guarantees on the behaviour. It has been recently shown that controller synthesis for Markov decision processes and fLTL is decidable when all the bounds on frequencies are 1. As a step towards a complete quantitative solution, we show that the problem is decidable for the fragment fLTL\GU, where U does not occur in the scope of G (but still F can). Our solution is based on a novel translation of such quantitative formulae into equivalent deterministic automata.
AU - Forejt, Vojtěch
AU - Krčál, Jan
AU - Kretinsky, Jan
ID - 1594
TI - Controller synthesis for MDPs and frequency LTL\GU
VL - 9450
ER -
TY - CONF
AB - A drawing of a graph G is radial if the vertices of G are placed on concentric circles C1, . . . , Ck 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 Tóth.
AU - Fulek, Radoslav
AU - Pelsmajer, Michael
AU - Schaefer, Marcus
ID - 1595
TI - Hanani-Tutte for radial planarity
VL - 9411
ER -
TY - CHAP
AB - Let C={C1,...,Cn} denote a collection of translates of a regular convex k-gon in the plane with the stacking order. The collection C forms a visibility clique if for everyi < j the intersection Ci and (Ci ∩ Cj)\⋃i<l<jCl =∅.elements that are stacked between them, i.e., We show that if C forms a visibility clique its size is bounded from above by O(k4) thereby improving the upper bound of 22k from the aforementioned paper. We also obtain an upper bound of 22(k/2)+2 on the size of a visibility clique for homothetes of a convex (not necessarily regular) k-gon.
AU - Fulek, Radoslav
AU - Radoičić, Radoš
ID - 1596
SN - 978-3-319-27260-3
T2 - Graph Drawing and Network Visualization
TI - Vertical visibility among parallel polygons in three dimensions
VL - 9411
ER -
TY - JOUR
AB - We consider Markov decision processes (MDPs) with specifications given as Büchi (liveness) objectives, and examine the problem of computing the set of almost-sure winning vertices such that the objective can be ensured with probability 1 from these vertices. We study for the first time the average-case complexity of the classical algorithm for computing the set of almost-sure winning vertices for MDPs with Büchi objectives. Our contributions are as follows: First, we show that for MDPs with constant out-degree the expected number of iterations is at most logarithmic and the average-case running time is linear (as compared to the worst-case linear number of iterations and quadratic time complexity). Second, for the average-case analysis over all MDPs we show that the expected number of iterations is constant and the average-case running time is linear (again as compared to the worst-case linear number of iterations and quadratic time complexity). Finally we also show that when all MDPs are equally likely, the probability that the classical algorithm requires more than a constant number of iterations is exponentially small.
AU - Chatterjee, Krishnendu
AU - Joglekar, Manas
AU - Shah, Nisarg
ID - 1598
IS - 3
JF - Theoretical Computer Science
TI - Average case analysis of the classical algorithm for Markov decision processes with Büchi objectives
VL - 573
ER -
TY - CONF
AB - We propose a flexible exchange format for ω-automata, as typically used in formal verification, and implement support for it in a range of established tools. Our aim is to simplify the interaction of tools, helping the research community to build upon other people’s work. A key feature of the format is the use of very generic acceptance conditions, specified by Boolean combinations of acceptance primitives, rather than being limited to common cases such as Büchi, Streett, or Rabin. Such flexibility in the choice of acceptance conditions can be exploited in applications, for example in probabilistic model checking, and furthermore encourages the development of acceptance-agnostic tools for automata manipulations. The format allows acceptance conditions that are either state-based or transition-based, and also supports alternating automata.
AU - Babiak, Tomáš
AU - Blahoudek, František
AU - Duret Lutz, Alexandre
AU - Klein, Joachim
AU - Kretinsky, Jan
AU - Mueller, Daniel
AU - Parker, David
AU - Strejček, Jan
ID - 1601
TI - The Hanoi omega-automata format
VL - 9206
ER -
TY - JOUR
AB - Interprocedural analysis is at the heart of numerous applications in programming languages, such as alias analysis, constant propagation, etc. Recursive state machines (RSMs) are standard models for interprocedural analysis. We consider a general framework with RSMs where the transitions are labeled from a semiring, and path properties are algebraic with semiring operations. RSMs with algebraic path properties can model interprocedural dataflow analysis problems, the shortest path problem, the most probable path problem, etc. The traditional algorithms for interprocedural analysis focus on path properties where the starting point is fixed as the entry point of a specific method. In this work, we consider possible multiple queries as required in many applications such as in alias analysis. The study of multiple queries allows us to bring in a very important algorithmic distinction between the resource usage of the one-time preprocessing vs for each individual query. The second aspect that we consider is that the control flow graphs for most programs have constant treewidth. Our main contributions are simple and implementable algorithms that supportmultiple queries for algebraic path properties for RSMs that have constant treewidth. Our theoretical results show that our algorithms have small additional one-time preprocessing, but can answer subsequent queries significantly faster as compared to the current best-known solutions for several important problems, such as interprocedural reachability and shortest path. We provide a prototype implementation for interprocedural reachability and intraprocedural shortest path that gives a significant speed-up on several benchmarks.
AU - Chatterjee, Krishnendu
AU - Ibsen-Jensen, Rasmus
AU - Pavlogiannis, Andreas
AU - Goyal, Prateesh
ID - 1602
IS - 1
JF - ACM SIGPLAN Notices
TI - Faster algorithms for algebraic path properties in recursive state machines with constant treewidth
VL - 50
ER -
TY - CONF
AB - For deterministic systems, a counterexample to a property can simply be an error trace, whereas counterexamples in probabilistic systems are necessarily more complex. For instance, a set of erroneous traces with a sufficient cumulative probability mass can be used. Since these are too large objects to understand and manipulate, compact representations such as subchains have been considered. In the case of probabilistic systems with non-determinism, the situation is even more complex. While a subchain for a given strategy (or scheduler, resolving non-determinism) is a straightforward choice, we take a different approach. Instead, we focus on the strategy itself, and extract the most important decisions it makes, and present its succinct representation.
The key tools we employ to achieve this are (1) introducing a concept of importance of a state w.r.t. the strategy, and (2) learning using decision trees. There are three main consequent advantages of our approach. Firstly, it exploits the quantitative information on states, stressing the more important decisions. Secondly, it leads to a greater variability and degree of freedom in representing the strategies. Thirdly, the representation uses a self-explanatory data structure. In summary, our approach produces more succinct and more explainable strategies, as opposed to e.g. binary decision diagrams. Finally, our experimental results show that we can extract several rules describing the strategy even for very large systems that do not fit in memory, and based on the rules explain the erroneous behaviour.
AU - Brázdil, Tomáš
AU - Chatterjee, Krishnendu
AU - Chmelik, Martin
AU - Fellner, Andreas
AU - Kretinsky, Jan
ID - 1603
TI - Counterexample explanation by learning small strategies in Markov decision processes
VL - 9206
ER -
TY - JOUR
AB - We consider the quantitative analysis problem for interprocedural control-flow graphs (ICFGs). The input consists of an ICFG, a positive weight function that assigns every transition a positive integer-valued number, and a labelling of the transitions (events) as good, bad, and neutral events. The weight function assigns to each transition a numerical value that represents ameasure of how good or bad an event is. The quantitative analysis problem asks whether there is a run of the ICFG where the ratio of the sum of the numerical weights of good events versus the sum of weights of bad events in the long-run is at least a given threshold (or equivalently, to compute the maximal ratio among all valid paths in the ICFG). The quantitative analysis problem for ICFGs can be solved in polynomial time, and we present an efficient and practical algorithm for the problem. We show that several problems relevant for static program analysis, such as estimating the worst-case execution time of a program or the average energy consumption of a mobile application, can be modeled in our framework. We have implemented our algorithm as a tool in the Java Soot framework. We demonstrate the effectiveness of our approach with two case studies. First, we show that our framework provides a sound approach (no false positives) for the analysis of inefficiently-used containers. Second, we show that our approach can also be used for static profiling of programs which reasons about methods that are frequently invoked. Our experimental results show that our tool scales to relatively large benchmarks, and discovers relevant and useful information that can be used to optimize performance of the programs.
AU - Chatterjee, Krishnendu
AU - Pavlogiannis, Andreas
AU - Velner, Yaron
ID - 1604
IS - 1
JF - Proceedings of the 42nd Annual ACM SIGPLAN-SIGACT
SN - 978-1-4503-3300-9
TI - Quantitative interprocedural analysis
VL - 50
ER -
TY - CONF
AB - Multiaffine hybrid automata (MHA) represent a powerful formalism to model complex dynamical systems. This formalism is particularly suited for the representation of biological systems which often exhibit highly non-linear behavior. In this paper, we consider the problem of parameter identification for MHA. We present an abstraction of MHA based on linear hybrid automata, which can be analyzed by the SpaceEx model checker. This abstraction enables a precise handling of time-dependent properties. We demonstrate the potential of our approach on a model of a genetic regulatory network and a myocyte model.
AU - Bogomolov, Sergiy
AU - Schilling, Christian
AU - Bartocci, Ezio
AU - Batt, Grégory
AU - Kong, Hui
AU - Grosu, Radu
ID - 1605
TI - Abstraction-based parameter synthesis for multiaffine systems
VL - 9434
ER -
TY - CONF
AB - In this paper, we present the first steps toward a runtime verification framework for monitoring hybrid and cyber-physical systems (CPS) development tools based on randomized differential testing. The development tools include hybrid systems reachability analysis tools, model-based development environments like Simulink/Stateflow (SLSF), etc. First, hybrid automaton models are randomly generated. Next, these hybrid automaton models are translated to a number of different tools (currently, SpaceEx, dReach, Flow*, HyCreate, and the MathWorks’ Simulink/Stateflow) using the HyST source transformation and translation tool. Then, the hybrid automaton models are executed in the different tools and their outputs are parsed. The final step is the differential comparison: the outputs of the different tools are compared. If the results do not agree (in the sense that an analysis or verification result from one tool does not match that of another tool, ignoring timeouts, etc.), a candidate bug is flagged and the model is saved for future analysis by the user. The process then repeats and the monitoring continues until the user terminates the process. We present preliminary results that have been useful in identifying a few bugs in the analysis methods of different development tools, and in an earlier version of HyST.
AU - Nguyen, Luan
AU - Schilling, Christian
AU - Bogomolov, Sergiy
AU - Johnson, Taylor
ID - 1606
SN - 978-3-319-23819-7
T2 - 6th International Conference
TI - Runtime verification for hybrid analysis tools
VL - 9333
ER -
TY - CONF
AB - We consider the core algorithmic problems related to verification of systems with respect to three classical quantitative properties, namely, the mean-payoff property, the ratio property, and the minimum initial credit for energy property. The algorithmic problem given a graph and a quantitative property asks to compute the optimal value (the infimum value over all traces) from every node of the graph. We consider graphs with constant treewidth, and it is well-known that the control-flow graphs of most programs have constant treewidth. Let n denote the number of nodes of a graph, m the number of edges (for constant treewidth graphs m=O(n)) and W the largest absolute value of the weights. Our main theoretical results are as follows. First, for constant treewidth graphs we present an algorithm that approximates the mean-payoff value within a multiplicative factor of ϵ in time O(n⋅log(n/ϵ)) and linear space, as compared to the classical algorithms that require quadratic time. Second, for the ratio property we present an algorithm that for constant treewidth graphs works in time O(n⋅log(|a⋅b|))=O(n⋅log(n⋅W)), when the output is ab, as compared to the previously best known algorithm with running time O(n2⋅log(n⋅W)). Third, for the minimum initial credit problem we show that (i) for general graphs the problem can be solved in O(n2⋅m) time and the associated decision problem can be solved in O(n⋅m) time, improving the previous known O(n3⋅m⋅log(n⋅W)) and O(n2⋅m) bounds, respectively; and (ii) for constant treewidth graphs we present an algorithm that requires O(n⋅logn) time, improving the previous known O(n4⋅log(n⋅W)) bound. We have implemented some of our algorithms and show that they present a significant speedup on standard benchmarks.
AU - Chatterjee, Krishnendu
AU - Ibsen-Jensen, Rasmus
AU - Pavlogiannis, Andreas
ID - 1607
TI - Faster algorithms for quantitative verification in constant treewidth graphs
VL - 9206
ER -
TY - CONF
AB - The synthesis problem asks for the automatic construction of a system from its specification. In the traditional setting, the system is “constructed from scratch” rather than composed from reusable components. However, this is rare in practice, and almost every non-trivial software system relies heavily on the use of libraries of reusable components. Recently, Lustig and Vardi introduced dataflow and controlflow synthesis from libraries of reusable components. They proved that dataflow synthesis is undecidable, while controlflow synthesis is decidable. The problem of controlflow synthesis from libraries of probabilistic components was considered by Nain, Lustig and Vardi, and was shown to be decidable for qualitative analysis (that asks that the specification be satisfied with probability 1). Our main contribution for controlflow synthesis from probabilistic components is to establish better complexity bounds for the qualitative analysis problem, and to show that the more general quantitative problem is undecidable. For the qualitative analysis, we show that the problem (i) is EXPTIME-complete when the specification is given as a deterministic parity word automaton, improving the previously known 2EXPTIME upper bound; and (ii) belongs to UP ∩ coUP and is parity-games hard, when the specification is given directly as a parity condition on the components, improving the previously known EXPTIME upper bound.
AU - Chatterjee, Krishnendu
AU - Doyen, Laurent
AU - Vardi, Moshe
ID - 1609
SN - 978-3-662-47665-9
T2 - 42nd International Colloquium
TI - The complexity of synthesis from probabilistic components
VL - 9135
ER -
TY - CONF
AB - The edit distance between two words w1, w2 is the minimal number of word operations (letter insertions, deletions, and substitutions) necessary to transform w1 to w2. The edit distance generalizes to languages L1,L2, where the edit distance is the minimal number k such that for every word from L1 there exists a word in L2 with edit distance at most k. We study the edit distance computation problem between pushdown automata and their subclasses. The problem of computing edit distance to pushdown automata is undecidable, and in practice, the interesting question is to compute the edit distance from a pushdown automaton (the implementation, a standard model for programs with recursion) to a regular language (the specification). In this work, we present a complete picture of decidability and complexity for deciding whether, for a given threshold k, the edit distance from a pushdown automaton to a finite automaton is at most k.
AU - Chatterjee, Krishnendu
AU - Henzinger, Thomas A
AU - Ibsen-Jensen, Rasmus
AU - Otop, Jan
ID - 1610
IS - Part II
SN - 978-3-662-47665-9
T2 - 42nd International Colloquium
TI - Edit distance for pushdown automata
VL - 9135
ER -
TY - JOUR
AB - Biosensors for signaling molecules allow the study of physiological processes by bringing together the fields of protein engineering, fluorescence imaging, and cell biology. Construction of genetically encoded biosensors generally relies on the availability of a binding "core" that is both specific and stable, which can then be combined with fluorescent molecules to create a sensor. However, binding proteins with the desired properties are often not available in nature and substantial improvement to sensors can be required, particularly with regard to their durability. Ancestral protein reconstruction is a powerful protein-engineering tool able to generate highly stable and functional proteins. In this work, we sought to establish the utility of ancestral protein reconstruction to biosensor development, beginning with the construction of an l-arginine biosensor. l-arginine, as the immediate precursor to nitric oxide, is an important molecule in many physiological contexts including brain function. Using a combination of ancestral reconstruction and circular permutation, we constructed a Förster resonance energy transfer (FRET) biosensor for l-arginine (cpFLIPR). cpFLIPR displays high sensitivity and specificity, with a Kd of ∼14 μM and a maximal dynamic range of 35%. Importantly, cpFLIPR was highly robust, enabling accurate l-arginine measurement at physiological temperatures. We established that cpFLIPR is compatible with two-photon excitation fluorescence microscopy and report l-arginine concentrations in brain tissue.
AU - Whitfield, Jason
AU - Zhang, William
AU - Herde, Michel
AU - Clifton, Ben
AU - Radziejewski, Johanna
AU - Janovjak, Harald L
AU - Henneberger, Christian
AU - Jackson, Colin
ID - 1611
IS - 9
JF - Protein Science
TI - Construction of a robust and sensitive arginine biosensor through ancestral protein reconstruction
VL - 24
ER -
TY - JOUR
AB - GABAergic perisoma-inhibiting fast-spiking interneurons (PIIs) effectively control the activity of large neuron populations by their wide axonal arborizations. It is generally assumed that the output of one PII to its target cells is strong and rapid. Here, we show that, unexpectedly, both strength and time course of PII-mediated perisomatic inhibition change with distance between synaptically connected partners in the rodent hippocampus. Synaptic signals become weaker due to lower contact numbers and decay more slowly with distance, very likely resulting from changes in GABAA receptor subunit composition. When distance-dependent synaptic inhibition is introduced to a rhythmically active neuronal network model, randomly driven principal cell assemblies are strongly synchronized by the PIIs, leading to higher precision in principal cell spike times than in a network with uniform synaptic inhibition.
AU - Strüber, Michael
AU - Jonas, Peter M
AU - Bartos, Marlene
ID - 1614
IS - 4
JF - PNAS
TI - Strength and duration of perisomatic GABAergic inhibition depend on distance between synaptically connected cells
VL - 112
ER -
TY - JOUR
AB - Loss-of-function mutations in the synaptic adhesion protein Neuroligin-4 are among the most common genetic abnormalities associated with autism spectrum disorders, but little is known about the function of Neuroligin-4 and the consequences of its loss. We assessed synaptic and network characteristics in Neuroligin-4 knockout mice, focusing on the hippocampus as a model brain region with a critical role in cognition and memory, and found that Neuroligin-4 deletion causes subtle defects of the protein composition and function of GABAergic synapses in the hippocampal CA3 region. Interestingly, these subtle synaptic changes are accompanied by pronounced perturbations of γ-oscillatory network activity, which has been implicated in cognitive function and is altered in multiple psychiatric and neurodevelopmental disorders. Our data provide important insights into the mechanisms by which Neuroligin-4-dependent GABAergic synapses may contribute to autism phenotypes and indicate new strategies for therapeutic approaches.
AU - Hammer, Matthieu
AU - Krueger Burg, Dilja
AU - Tuffy, Liam
AU - Cooper, Benjamin
AU - Taschenberger, Holger
AU - Goswami, Sarit
AU - Ehrenreich, Hannelore
AU - Jonas, Peter M
AU - Varoqueaux, Frederique
AU - Rhee, Jeong
AU - Brose, Nils
ID - 1615
IS - 3
JF - Cell Reports
TI - Perturbed hippocampal synaptic inhibition and γ-oscillations in a neuroligin-4 knockout mouse model of autism
VL - 13
ER -
TY - JOUR
AB - CCL19 and CCL21 are chemokines involved in the trafficking of immune cells, particularly within the lymphatic system, through activation of CCR7. Concurrent expression of PSGL-1 and CCR7 in naive T-cells enhances recruitment of these cells to secondary lymphoid organs by CCL19 and CCL21. Here the solution structure of CCL19 is reported. It contains a canonical chemokine domain. Chemical shift mapping shows the N-termini of PSGL-1 and CCR7 have overlapping binding sites for CCL19 and binding is competitive. Implications for the mechanism of PSGL-1's enhancement of resting T-cell recruitment are discussed.
AU - Veldkamp, Christopher
AU - Kiermaier, Eva
AU - Gabel Eissens, Skylar
AU - Gillitzer, Miranda
AU - Lippner, David
AU - Disilvio, Frank
AU - Mueller, Casey
AU - Wantuch, Paeton
AU - Chaffee, Gary
AU - Famiglietti, Michael
AU - Zgoba, Danielle
AU - Bailey, Asha
AU - Bah, Yaya
AU - Engebretson, Samantha
AU - Graupner, David
AU - Lackner, Emily
AU - Larosa, Vincent
AU - Medeiros, Tysha
AU - Olson, Michael
AU - Phillips, Andrew
AU - Pyles, Harley
AU - Richard, Amanda
AU - Schoeller, Scott
AU - Touzeau, Boris
AU - Williams, Larry
AU - Sixt, Michael K
AU - Peterson, Francis
ID - 1618
IS - 27
JF - Biochemistry
TI - Solution structure of CCL19 and identification of overlapping CCR7 and PSGL-1 binding sites
VL - 54
ER -
TY - JOUR
AB - Background
Photosynthetic cyanobacteria are attractive for a range of biotechnological applications including biofuel production. However, due to slow growth, screening of mutant libraries using microtiter plates is not feasible.
Results
We present a method for high-throughput, single-cell analysis and sorting of genetically engineered l-lactate-producing strains of Synechocystis sp. PCC6803. A microfluidic device is used to encapsulate single cells in picoliter droplets, assay the droplets for l-lactate production, and sort strains with high productivity. We demonstrate the separation of low- and high-producing reference strains, as well as enrichment of a more productive l-lactate-synthesizing population after UV-induced mutagenesis. The droplet platform also revealed population heterogeneity in photosynthetic growth and lactate production, as well as the presence of metabolically stalled cells.
Conclusions
The workflow will facilitate metabolic engineering and directed evolution studies and will be useful in studies of cyanobacteria biochemistry and physiology.
AU - Hammar, Petter
AU - Angermayr, Andreas
AU - Sjostrom, Staffan
AU - Van Der Meer, Josefin
AU - Hellingwerf, Klaas
AU - Hudson, Elton
AU - Joensson, Hakaan
ID - 1623
IS - 1
JF - Biotechnology for Biofuels
TI - Single-cell screening of photosynthetic growth and lactate production by cyanobacteria
VL - 8
ER -
TY - JOUR
AB - Population structure can facilitate evolution of cooperation. In a structured population, cooperators can form clusters which resist exploitation by defectors. Recently, it was observed that a shift update rule is an extremely strong amplifier of cooperation in a one dimensional spatial model. For the shift update rule, an individual is chosen for reproduction proportional to fecundity; the offspring is placed next to the parent; a random individual dies. Subsequently, the population is rearranged (shifted) until all individual cells are again evenly spaced out. For large population size and a one dimensional population structure, the shift update rule favors cooperation for any benefit-to-cost ratio greater than one. But every attempt to generalize shift updating to higher dimensions while maintaining its strong effect has failed. The reason is that in two dimensions the clusters are fragmented by the movements caused by rearranging the cells. Here we introduce the natural phenomenon of a repulsive force between cells of different types. After a birth and death event, the cells are being rearranged minimizing the overall energy expenditure. If the repulsive force is sufficiently high, shift becomes a strong promoter of cooperation in two dimensions.
AU - Pavlogiannis, Andreas
AU - Chatterjee, Krishnendu
AU - Adlam, Ben
AU - Nowak, Martin
ID - 1624
JF - Scientific Reports
TI - Cellular cooperation with shift updating and repulsion
VL - 5
ER -
TY - CONF
AB - In recent years we have seen numerous improvements on 3D scanning and tracking of human faces, greatly advancing the creation of digital doubles for film and video games. However, despite the high-resolution quality of the reconstruction approaches available, current methods are unable to capture one of the most important regions of the face - the eye region. In this work we present the first method for detailed spatio-temporal reconstruction of eyelids. Tracking and reconstructing eyelids is extremely challenging, as this region exhibits very complex and unique skin deformation where skin is folded under while opening the eye. Furthermore, eyelids are often only partially visible and obstructed due to selfocclusion and eyelashes. Our approach is to combine a geometric deformation model with image data, leveraging multi-view stereo, optical flow, contour tracking and wrinkle detection from local skin appearance. Our deformation model serves as a prior that enables reconstruction of eyelids even under strong self-occlusions caused by rolling and folding skin as the eye opens and closes. The output is a person-specific, time-varying eyelid reconstruction with anatomically plausible deformations. Our high-resolution detailed eyelids couple naturally with current facial performance capture approaches. As a result, our method can largely increase the fidelity of facial capture and the creation of digital doubles.
AU - Bermano, Amit
AU - Beeler, Thabo
AU - Kozlov, Yeara
AU - Bradley, Derek
AU - Bickel, Bernd
AU - Gross, Markus
ID - 1625
IS - 4
TI - Detailed spatio-temporal reconstruction of eyelids
VL - 34
ER -
TY - CONF
AB - This paper introduces "OmniAD," a novel data-driven pipeline to model and acquire the aerodynamics of three-dimensional rigid objects. Traditionally, aerodynamics are examined through elaborate wind tunnel experiments or expensive fluid dynamics computations, and are only measured for a small number of discrete wind directions. OmniAD allows the evaluation of aerodynamic forces, such as drag and lift, for any incoming wind direction using a novel representation based on spherical harmonics. Our datadriven technique acquires the aerodynamic properties of an object simply by capturing its falling motion using a single camera. Once model parameters are estimated, OmniAD enables realistic realtime simulation of rigid bodies, such as the tumbling and gliding of leaves, without simulating the surrounding air. In addition, we propose an intuitive user interface based on OmniAD to interactively design three-dimensional kites that actually fly. Various nontraditional kites were designed to demonstrate the physical validity of our model.
AU - Martin, Tobias
AU - Umetani, Nobuyuki
AU - Bickel, Bernd
ID - 1626
IS - 4
TI - OmniAD: Data-driven omni-directional aerodynamics
VL - 34
ER -
TY - CONF
AB - We present a computational tool for fabrication-oriented design of flexible rod meshes. Given a deformable surface and a set of deformed poses as input, our method automatically computes a printable rod mesh that, once manufactured, closely matches the input poses under the same boundary conditions. The core of our method is formed by an optimization scheme that adjusts the cross-sectional profiles of the rods and their rest centerline in order to best approximate the target deformations. This approach allows us to locally control the bending and stretching resistance of the surface with a single material, yielding high design flexibility and low fabrication cost.
AU - Pérez, Jesús
AU - Thomaszewski, Bernhard
AU - Coros, Stelian
AU - Bickel, Bernd
AU - Canabal, José
AU - Sumner, Robert
AU - Otaduy, Miguel
ID - 1627
IS - 4
TI - Design and fabrication of flexible rod meshes
VL - 34
ER -
TY - CONF
AB - We propose a method for fabricating deformable objects with spatially varying elasticity using 3D printing. Using a single, relatively stiff printer material, our method designs an assembly of smallscale microstructures that have the effect of a softer material at the object scale, with properties depending on the microstructure used in each part of the object. We build on work in the area of metamaterials, using numerical optimization to design tiled microstructures with desired properties, but with the key difference that our method designs families of related structures that can be interpolated to smoothly vary the material properties over a wide range. To create an object with spatially varying elastic properties, we tile the object's interior with microstructures drawn from these families, generating a different microstructure for each cell using an efficient algorithm to select compatible structures for neighboring cells. We show results computed for both 2D and 3D objects, validating several 2D and 3D printed structures using standard material tests as well as demonstrating various example applications.
AU - Schumacher, Christian
AU - Bickel, Bernd
AU - Rys, Jan
AU - Marschner, Steve
AU - Daraio, Chiara
AU - Gross, Markus
ID - 1628
IS - 4
TI - Microstructures to control elasticity in 3D printing
VL - 34
ER -
TY - CONF
AB - We present a method to learn and propagate shape placements in 2D polygonal scenes from a few examples provided by a user. The placement of a shape is modeled as an oriented bounding box. Simple geometric relationships between this bounding box and nearby scene polygons define a feature set for the placement. The feature sets of all example placements are then used to learn a probabilistic model over all possible placements and scenes. With this model, we can generate a new set of placements with similar geometric relationships in any given scene. We introduce extensions that enable propagation and generation of shapes in 3D scenes, as well as the application of a learned modeling session to large scenes without additional user interaction. These concepts allow us to generate complex scenes with thousands of objects with relatively little user interaction.
AU - Guerrero, Paul
AU - Jeschke, Stefan
AU - Wimmer, Michael
AU - Wonka, Peter
ID - 1630
IS - 4
TI - Learning shape placements by example
VL - 34
ER -
TY - CONF
AB - This paper presents a liquid simulation technique that enforces the incompressibility condition using a stream function solve instead of a pressure projection. Previous methods have used stream function techniques for the simulation of detailed single-phase flows, but a formulation for liquid simulation has proved elusive in part due to the free surface boundary conditions. In this paper, we introduce a stream function approach to liquid simulations with novel boundary conditions for free surfaces, solid obstacles, and solid-fluid coupling.
Although our approach increases the dimension of the linear system necessary to enforce incompressibility, it provides interesting and surprising benefits. First, the resulting flow is guaranteed to be divergence-free regardless of the accuracy of the solve. Second, our free-surface boundary conditions guarantee divergence-free motion even in the un-simulated air phase, which enables two-phase flow simulation by only computing a single phase. We implemented this method using a variant of FLIP simulation which only samples particles within a narrow band of the liquid surface, and we illustrate the effectiveness of our method for detailed two-phase flow simulations with complex boundaries, detailed bubble interactions, and two-way solid-fluid coupling.
AU - Ando, Ryoichi
AU - Thuerey, Nils
AU - Wojtan, Christopher J
ID - 1632
IS - 4
TI - A stream function solver for liquid simulations
VL - 34
ER -
TY - CONF
AB - We present a method for simulating brittle fracture under the assumptions of quasi-static linear elastic fracture mechanics (LEFM). Using the boundary element method (BEM) and Lagrangian crack-fronts, we produce highly detailed fracture surfaces. The computational cost of the BEM is alleviated by using a low-resolution mesh and interpolating the resulting stress intensity factors when propagating the high-resolution crack-front.
Our system produces physics-based fracture surfaces with high spatial and temporal resolution, taking spatial variation of material toughness and/or strength into account. It also allows for crack initiation to be handled separately from crack propagation, which is not only more reasonable from a physics perspective, but can also be used to control the simulation.
Separating the resolution of the crack-front from the resolution of the computational mesh increases the efficiency and therefore the amount of visual detail on the resulting fracture surfaces. The BEM also allows us to re-use previously computed blocks of the system matrix.
AU - Hahn, David
AU - Wojtan, Christopher J
ID - 1633
IS - 4
TI - High-resolution brittle fracture simulation with boundary elements
VL - 34
ER -
TY - CONF
AB - Simulating the delightful dynamics of soap films, bubbles, and foams has traditionally required the use of a fully three-dimensional many-phase Navier-Stokes solver, even though their visual appearance is completely dominated by the thin liquid surface. We depart from earlier work on soap bubbles and foams by noting that their dynamics are naturally described by a Lagrangian vortex sheet model in which circulation is the primary variable. This leads us to derive a novel circulation-preserving surface-only discretization of foam dynamics driven by surface tension on a non-manifold triangle mesh. We represent the surface using a mesh-based multimaterial surface tracker which supports complex bubble topology changes, and evolve the surface according to the ambient air flow induced by a scalar circulation field stored on the mesh. Surface tension forces give rise to a simple update rule for circulation, even at non-manifold Plateau borders, based on a discrete measure of signed scalar mean curvature. We further incorporate vertex constraints to enable the interaction of soap films with wires. The result is a method that is at once simple, robust, and efficient, yet able to capture an array of soap films behaviors including foam rearrangement, catenoid collapse, blowing bubbles, and double bubbles being pulled apart.
AU - Da, Fang
AU - Batty, Christopher
AU - Wojtan, Christopher J
AU - Grinspun, Eitan
ID - 1634
IS - 4
TI - Double bubbles sans toil and trouble: discrete circulation-preserving vortex sheets for soap films and foams
VL - 34
ER -
TY - JOUR
AB - We calculate a Ricci curvature lower bound for some classical examples of random walks, namely, a chain on a slice of the n-dimensional discrete cube (the so-called Bernoulli-Laplace model) and the random transposition shuffle of the symmetric group of permutations on n letters.
AU - Erbar, Matthias
AU - Maas, Jan
AU - Tetali, Prasad
ID - 1635
IS - 4
JF - Annales de la faculté des sciences de Toulouse
TI - Discrete Ricci curvature bounds for Bernoulli-Laplace and random transposition models
VL - 24
ER -
TY - CONF
AB - Constraint Satisfaction Problem (CSP) is a fundamental algorithmic problem that appears in many areas of Computer Science. It can be equivalently stated as computing a homomorphism R→ΓΓ between two relational structures, e.g. between two directed graphs. Analyzing its complexity has been a prominent research direction, especially for the fixed template CSPs where the right side ΓΓ is fixed and the left side R is unconstrained.
Far fewer results are known for the hybrid setting that restricts both sides simultaneously. It assumes that R belongs to a certain class of relational structures (called a structural restriction in this paper). We study which structural restrictions are effective, i.e. there exists a fixed template ΓΓ (from a certain class of languages) for which the problem is tractable when R is restricted, and NP-hard otherwise. We provide a characterization for structural restrictions that are closed under inverse homomorphisms. The criterion is based on the chromatic number of a relational structure defined in this paper; it generalizes the standard chromatic number of a graph.
As our main tool, we use the algebraic machinery developed for fixed template CSPs. To apply it to our case, we introduce a new construction called a “lifted language”. We also give a characterization for structural restrictions corresponding to minor-closed families of graphs, extend results to certain Valued CSPs (namely conservative valued languages), and state implications for (valued) CSPs with ordered variables and for the maximum weight independent set problem on some restricted families of graphs.
AU - Kolmogorov, Vladimir
AU - Rolinek, Michal
AU - Takhanov, Rustem
ID - 1636
SN - 978-3-662-48970-3
T2 - 26th International Symposium
TI - Effectiveness of structural restrictions for hybrid CSPs
VL - 9472
ER -
TY - CONF
AB - An instance of the Valued Constraint Satisfaction Problem (VCSP) is given by a finite set of variables, a finite domain of labels, and a sum of functions, each function depending on a subset of the variables. Each function can take finite values specifying costs of assignments of labels to its variables or the infinite value, which indicates an infeasible assignment. The goal is to find an assignment of labels to the variables that minimizes the sum. We study, assuming that P ≠ NP, how the complexity of this very general problem depends on the set of functions allowed in the instances, the so-called constraint language. The case when all allowed functions take values in {0, ∞} corresponds to ordinary CSPs, where one deals only with the feasibility issue and there is no optimization. This case is the subject of the Algebraic CSP Dichotomy Conjecture predicting for which constraint languages CSPs are tractable (i.e. solvable in polynomial time) and for which NP-hard. The case when all allowed functions take only finite values corresponds to finite-valued CSP, where the feasibility aspect is trivial and one deals only with the optimization issue. The complexity of finite-valued CSPs was fully classified by Thapper and Zivny. An algebraic necessary condition for tractability of a general-valued CSP with a fixed constraint language was recently given by Kozik and Ochremiak. As our main result, we prove that if a constraint language satisfies this algebraic necessary condition, and the feasibility CSP (i.e. the problem of deciding whether a given instance has a feasible solution) corresponding to the VCSP with this language is tractable, then the VCSP is tractable. The algorithm is a simple combination of the assumed algorithm for the feasibility CSP and the standard LP relaxation. As a corollary, we obtain that a dichotomy for ordinary CSPs would imply a dichotomy for general-valued CSPs.
AU - Kolmogorov, Vladimir
AU - Krokhin, Andrei
AU - Rolinek, Michal
ID - 1637
TI - The complexity of general-valued CSPs
ER -
TY - JOUR
AB - The mitochondrial respiratory chain, also known as the electron transport chain (ETC), is crucial to life, and energy production in the form of ATP is the main mitochondrial function. Three proton-translocating enzymes of the ETC, namely complexes I, III and IV, generate proton motive force, which in turn drives ATP synthase (complex V). The atomic structures and basic mechanisms of most respiratory complexes have previously been established, with the exception of complex I, the largest complex in the ETC. Recently, the crystal structure of the entire complex I was solved using a bacterial enzyme. The structure provided novel insights into the core architecture of the complex, the electron transfer and proton translocation pathways, as well as the mechanism that couples these two processes.
AU - Sazanov, Leonid A
ID - 1638
IS - 6
JF - Nature Reviews Molecular Cell Biology
TI - A giant molecular proton pump: structure and mechanism of respiratory complex I
VL - 16
ER -
TY - JOUR
AB - In this paper the optimal transport and the metamorphosis perspectives are combined. For a pair of given input images geodesic paths in the space of images are defined as minimizers of a resulting path energy. To this end, the underlying Riemannian metric measures the rate of transport cost and the rate of viscous dissipation. Furthermore, the model is capable to deal with strongly varying image contrast and explicitly allows for sources and sinks in the transport equations which are incorporated in the metric related to the metamorphosis approach by Trouvé and Younes. In the non-viscous case with source term existence of geodesic paths is proven in the space of measures. The proposed model is explored on the range from merely optimal transport to strongly dissipative dynamics. For this model a robust and effective variational time discretization of geodesic paths is proposed. This requires to minimize a discrete path energy consisting of a sum of consecutive image matching functionals. These functionals are defined on corresponding pairs of intensity functions and on associated pairwise matching deformations. Existence of time discrete geodesics is demonstrated. Furthermore, a finite element implementation is proposed and applied to instructive test cases and to real images. In the non-viscous case this is compared to the algorithm proposed by Benamou and Brenier including a discretization of the source term. Finally, the model is generalized to define discrete weighted barycentres with applications to textures and objects.
AU - Maas, Jan
AU - Rumpf, Martin
AU - Schönlieb, Carola
AU - Simon, Stefan
ID - 1639
IS - 6
JF - ESAIM: Mathematical Modelling and Numerical Analysis
TI - A generalized model for optimal transport of images including dissipation and density modulation
VL - 49
ER -
TY - JOUR
AB - Auxin and cytokinin are key endogenous regulators of plant development. Although cytokinin-mediated modulation of auxin distribution is a developmentally crucial hormonal interaction, its molecular basis is largely unknown. Here we show a direct regulatory link between cytokinin signalling and the auxin transport machinery uncovering a mechanistic framework for cytokinin-auxin cross-talk. We show that the CYTOKININ RESPONSE FACTORS (CRFs), transcription factors downstream of cytokinin perception, transcriptionally control genes encoding PIN-FORMED (PIN) auxin transporters at a specific PIN CYTOKININ RESPONSE ELEMENT (PCRE) domain. Removal of this cis-regulatory element effectively uncouples PIN transcription from the CRF-mediated cytokinin regulation and attenuates plant cytokinin sensitivity. We propose that CRFs represent a missing cross-talk component that fine-tunes auxin transport capacity downstream of cytokinin signalling to control plant development.
AU - Šimášková, Mária
AU - O'Brien, José
AU - Khan-Djamei, Mamoona
AU - Van Noorden, Giel
AU - Ötvös, Krisztina
AU - Vieten, Anne
AU - De Clercq, Inge
AU - Van Haperen, Johanna
AU - Cuesta, Candela
AU - Hoyerová, Klára
AU - Vanneste, Steffen
AU - Marhavy, Peter
AU - Wabnik, Krzysztof T
AU - Van Breusegem, Frank
AU - Nowack, Moritz
AU - Murphy, Angus
AU - Friml, Jiřĺ
AU - Weijers, Dolf
AU - Beeckman, Tom
AU - Benková, Eva
ID - 1640
JF - Nature Communications
TI - Cytokinin response factors regulate PIN-FORMED auxin transporters
VL - 6
ER -
TY - JOUR
AB - The Hanani-Tutte theorem is a classical result proved for the first time in the 1930s that characterizes planar graphs as graphs that admit a drawing in the plane in which every pair of edges not sharing a vertex cross an even number of times. We generalize this result to clustered graphs with two disjoint clusters, and show that a straightforward extension to flat clustered graphs with three or more disjoint clusters is not possible. For general clustered graphs we show a variant of the Hanani-Tutte theorem in the case when each cluster induces a connected subgraph. Di Battista and Frati proved that clustered planarity of embedded clustered graphs whose every face is incident to at most five vertices can be tested in polynomial time. We give a new and short proof of this result, using the matroid intersection algorithm.
AU - Fulek, Radoslav
AU - Kynčl, Jan
AU - Malinovič, Igor
AU - Pálvölgyi, Dömötör
ID - 1642
IS - 4
JF - Electronic Journal of Combinatorics
TI - Clustered planarity testing revisited
VL - 22
ER -
TY - CONF
AB - Increasing the computational complexity of evaluating a hash function, both for the honest users as well as for an adversary, is a useful technique employed for example in password-based cryptographic schemes to impede brute-force attacks, and also in so-called proofs of work (used in protocols like Bitcoin) to show that a certain amount of computation was performed by a legitimate user. A natural approach to adjust the complexity of a hash function is to iterate it c times, for some parameter c, in the hope that any query to the scheme requires c evaluations of the underlying hash function. However, results by Dodis et al. (Crypto 2012) imply that plain iteration falls short of achieving this goal, and designing schemes which provably have such a desirable property remained an open problem. This paper formalizes explicitly what it means for a given scheme to amplify the query complexity of a hash function. In the random oracle model, the goal of a secure query-complexity amplifier (QCA) scheme is captured as transforming, in the sense of indifferentiability, a random oracle allowing R queries (for the adversary) into one provably allowing only r < R queries. Turned around, this means that making r queries to the scheme requires at least R queries to the actual random oracle. Second, a new scheme, called collision-free iteration, is proposed and proven to achieve c-fold QCA for both the honest parties and the adversary, for any fixed parameter c.
AU - Demay, Grégory
AU - Gazi, Peter
AU - Maurer, Ueli
AU - Tackmann, Björn
ID - 1644
TI - Query-complexity amplification for random oracles
VL - 9063
ER -
TY - CONF
AB - Secret-key constructions are often proved secure in a model where one or more underlying components are replaced by an idealized oracle accessible to the attacker. This model gives rise to information-theoretic security analyses, and several advances have been made in this area over the last few years. This paper provides a systematic overview of what is achievable in this model, and how existing works fit into this view.
AU - Gazi, Peter
AU - Tessaro, Stefano
ID - 1645
T2 - 2015 IEEE Information Theory Workshop
TI - Secret-key cryptography from ideal primitives: A systematic verview
ER -
TY - CONF
AB - A pseudorandom function (PRF) is a keyed function F : K × X → Y where, for a random key k ∈ K, the function F(k, ·) is indistinguishable from a uniformly random function, given black-box access. A key-homomorphic PRF has the additional feature that for any keys k, k' and any input x, we have F(k+k', x) = F(k, x)⊕F(k', x) for some group operations +,⊕ on K and Y, respectively. A constrained PRF for a family of setsS ⊆ P(X) has the property that, given any key k and set S ∈ S, one can efficiently compute a “constrained” key kS that enables evaluation of F(k, x) on all inputs x ∈ S, while the values F(k, x) for x /∈ S remain pseudorandom even given kS. In this paper we construct PRFs that are simultaneously constrained and key homomorphic, where the homomorphic property holds even for constrained keys. We first show that the multilinear map-based bit-fixing and circuit-constrained PRFs of Boneh and Waters (Asiacrypt 2013) can be modified to also be keyhomomorphic. We then show that the LWE-based key-homomorphic PRFs of Banerjee and Peikert (Crypto 2014) are essentially already prefix-constrained PRFs, using a (non-obvious) definition of constrained keys and associated group operation. Moreover, the constrained keys themselves are pseudorandom, and the constraining and evaluation functions can all be computed in low depth. As an application of key-homomorphic constrained PRFs,we construct a proxy re-encryption schemewith fine-grained access control. This scheme allows storing encrypted data on an untrusted server, where each file can be encrypted relative to some attributes, so that only parties whose constrained keys match the attributes can decrypt. Moreover, the server can re-key (arbitrary subsets of) the ciphertexts without learning anything about the plaintexts, thus permitting efficient and finegrained revocation.
AU - Banerjee, Abishek
AU - Fuchsbauer, Georg
AU - Peikert, Chris
AU - Pietrzak, Krzysztof Z
AU - Stevens, Sophie
ID - 1646
SN - 978-3-662-46496-0
T2 - 12th Theory of Cryptography Conference
TI - Key-homomorphic constrained pseudorandom functions
VL - 9015
ER -
TY - CONF
AB - Round-optimal blind signatures are notoriously hard to construct in the standard model, especially in the malicious-signer model, where blindness must hold under adversarially chosen keys. This is substantiated by several impossibility results. The only construction that can be termed theoretically efficient, by Garg and Gupta (Eurocrypt’14), requires complexity leveraging, inducing an exponential security loss. We present a construction of practically efficient round-optimal blind signatures in the standard model. It is conceptually simple and builds on the recent structure-preserving signatures on equivalence classes (SPSEQ) from Asiacrypt’14. While the traditional notion of blindness follows from standard assumptions, we prove blindness under adversarially chosen keys under an interactive variant of DDH. However, we neither require non-uniform assumptions nor complexity leveraging. We then show how to extend our construction to partially blind signatures and to blind signatures on message vectors, which yield a construction of one-show anonymous credentials à la “anonymous credentials light” (CCS’13) in the standard model. Furthermore, we give the first SPS-EQ construction under noninteractive assumptions and show how SPS-EQ schemes imply conventional structure-preserving signatures, which allows us to apply optimality results for the latter to SPS-EQ.
AU - Fuchsbauer, Georg
AU - Hanser, Christian
AU - Slamanig, Daniel
ID - 1647
TI - Practical round-optimal blind signatures in the standard model
VL - 9216
ER -
TY - CONF
AB - Generalized Selective Decryption (GSD), introduced by Panjwani [TCC’07], is a game for a symmetric encryption scheme Enc that captures the difficulty of proving adaptive security of certain protocols, most notably the Logical Key Hierarchy (LKH) multicast encryption protocol. In the GSD game there are n keys k1,..., kn, which the adversary may adaptively corrupt (learn); moreover, it can ask for encryptions Encki (kj) of keys under other keys. The adversary’s task is to distinguish keys (which it cannot trivially compute) from random. Proving the hardness of GSD assuming only IND-CPA security of Enc is surprisingly hard. Using “complexity leveraging” loses a factor exponential in n, which makes the proof practically meaningless. We can think of the GSD game as building a graph on n vertices, where we add an edge i → j when the adversary asks for an encryption of kj under ki. If restricted to graphs of depth ℓ, Panjwani gave a reduction that loses only a factor exponential in ℓ (not n). To date, this is the only non-trivial result known for GSD. In this paper we give almost-polynomial reductions for large classes of graphs. Most importantly, we prove the security of the GSD game restricted to trees losing only a quasi-polynomial factor n3 log n+5. Trees are an important special case capturing real-world protocols like the LKH protocol. Our new bound improves upon Panjwani’s on some LKH variants proposed in the literature where the underlying tree is not balanced. Our proof builds on ideas from the “nested hybrids” technique recently introduced by Fuchsbauer et al. [Asiacrypt’14] for proving the adaptive security of constrained PRFs.
AU - Fuchsbauer, Georg
AU - Jafargholi, Zahra
AU - Pietrzak, Krzysztof Z
ID - 1648
TI - A quasipolynomial reduction for generalized selective decryption on trees
VL - 9215
ER -
TY - CONF
AB - We extend a commitment scheme based on the learning with errors over rings (RLWE) problem, and present efficient companion zeroknowledge proofs of knowledge. Our scheme maps elements from the ring (or equivalently, n elements from
AU - Benhamouda, Fabrice
AU - Krenn, Stephan
AU - Lyubashevsky, Vadim
AU - Pietrzak, Krzysztof Z
ID - 1649
TI - Efficient zero-knowledge proofs for commitments from learning with errors over rings
VL - 9326
ER -
TY - CONF
AB - We consider the task of deriving a key with high HILL entropy (i.e., being computationally indistinguishable from a key with high min-entropy) from an unpredictable source.
Previous to this work, the only known way to transform unpredictability into a key that was ϵ indistinguishable from having min-entropy was via pseudorandomness, for example by Goldreich-Levin (GL) hardcore bits. This approach has the inherent limitation that from a source with k bits of unpredictability entropy one can derive a key of length (and thus HILL entropy) at most k−2log(1/ϵ) bits. In many settings, e.g. when dealing with biometric data, such a 2log(1/ϵ) bit entropy loss in not an option. Our main technical contribution is a theorem that states that in the high entropy regime, unpredictability implies HILL entropy. Concretely, any variable K with |K|−d bits of unpredictability entropy has the same amount of so called metric entropy (against real-valued, deterministic distinguishers), which is known to imply the same amount of HILL entropy. The loss in circuit size in this argument is exponential in the entropy gap d, and thus this result only applies for small d (i.e., where the size of distinguishers considered is exponential in d).
To overcome the above restriction, we investigate if it’s possible to first “condense” unpredictability entropy and make the entropy gap small. We show that any source with k bits of unpredictability can be condensed into a source of length k with k−3 bits of unpredictability entropy. Our condenser simply “abuses" the GL construction and derives a k bit key from a source with k bits of unpredicatibily. The original GL theorem implies nothing when extracting that many bits, but we show that in this regime, GL still behaves like a “condenser" for unpredictability. This result comes with two caveats (1) the loss in circuit size is exponential in k and (2) we require that the source we start with has no HILL entropy (equivalently, one can efficiently check if a guess is correct). We leave it as an intriguing open problem to overcome these restrictions or to prove they’re inherent.
AU - Skórski, Maciej
AU - Golovnev, Alexander
AU - Pietrzak, Krzysztof Z
ID - 1650
TI - Condensed unpredictability
VL - 9134
ER -
TY - CONF
AB - We develop new theoretical tools for proving lower-bounds on the (amortized) complexity of certain functions in models of parallel computation. We apply the tools to construct a class of functions with high amortized memory complexity in the parallel Random Oracle Model (pROM); a variant of the standard ROM allowing for batches of simultaneous queries. In particular we obtain a new, more robust, type of Memory-Hard Functions (MHF); a security primitive which has recently been gaining acceptance in practice as an effective means of countering brute-force attacks on security relevant functions. Along the way we also demonstrate an important shortcoming of previous definitions of MHFs and give a new definition addressing the problem. The tools we develop represent an adaptation of the powerful pebbling paradigm (initially introduced by Hewitt and Paterson [HP70] and Cook [Coo73]) to a simple and intuitive parallel setting. We define a simple pebbling game Gp over graphs which aims to abstract parallel computation in an intuitive way. As a conceptual contribution we define a measure of pebbling complexity for graphs called cumulative complexity (CC) and show how it overcomes a crucial shortcoming (in the parallel setting) exhibited by more traditional complexity measures used in the past. As a main technical contribution we give an explicit construction of a constant in-degree family of graphs whose CC in Gp approaches maximality to within a polylogarithmic factor for any graph of equal size (analogous to the graphs of Tarjan et. al. [PTC76, LT82] for sequential pebbling games). Finally, for a given graph G and related function fG, we derive a lower-bound on the amortized memory complexity of fG in the pROM in terms of the CC of G in the game Gp.
AU - Alwen, Joel F
AU - Serbinenko, Vladimir
ID - 1652
T2 - Proceedings of the 47th annual ACM symposium on Theory of computing
TI - High parallel complexity graphs and memory-hard functions
ER -
TY - CONF
AB - HMAC and its variant NMAC are the most popular approaches to deriving a MAC (and more generally, a PRF) from a cryptographic hash function. Despite nearly two decades of research, their exact security still remains far from understood in many different contexts. Indeed, recent works have re-surfaced interest for {\em generic} attacks, i.e., attacks that treat the compression function of the underlying hash function as a black box.
Generic security can be proved in a model where the underlying compression function is modeled as a random function -- yet, to date, the question of proving tight, non-trivial bounds on the generic security of HMAC/NMAC even as a PRF remains a challenging open question.
In this paper, we ask the question of whether a small modification to HMAC and NMAC can allow us to exactly characterize the security of the resulting constructions, while only incurring little penalty with respect to efficiency. To this end, we present simple variants of NMAC and HMAC, for which we prove tight bounds on the generic PRF security, expressed in terms of numbers of construction and compression function queries necessary to break the construction. All of our constructions are obtained via a (near) {\em black-box} modification of NMAC and HMAC, which can be interpreted as an initial step of key-dependent message pre-processing.
While our focus is on PRF security, a further attractive feature of our new constructions is that they clearly defeat all recent generic attacks against properties such as state recovery and universal forgery. These exploit properties of the so-called ``functional graph'' which are not directly accessible in our new constructions.
AU - Gazi, Peter
AU - Pietrzak, Krzysztof Z
AU - Tessaro, Stefano
ID - 1654
TI - Generic security of NMAC and HMAC with input whitening
VL - 9453
ER -
TY - JOUR
AB - Quantifying behaviors of robots which were generated autonomously from task-independent objective functions is an important prerequisite for objective comparisons of algorithms and movements of animals. The temporal sequence of such a behavior can be considered as a time series and hence complexity measures developed for time series are natural candidates for its quantification. The predictive information and the excess entropy are such complexity measures. They measure the amount of information the past contains about the future and thus quantify the nonrandom structure in the temporal sequence. However, when using these measures for systems with continuous states one has to deal with the fact that their values will depend on the resolution with which the systems states are observed. For deterministic systems both measures will diverge with increasing resolution. We therefore propose a new decomposition of the excess entropy in resolution dependent and resolution independent parts and discuss how they depend on the dimensionality of the dynamics, correlations and the noise level. For the practical estimation we propose to use estimates based on the correlation integral instead of the direct estimation of the mutual information based on next neighbor statistics because the latter allows less control of the scale dependencies. Using our algorithm we are able to show how autonomous learning generates behavior of increasing complexity with increasing learning duration.
AU - Martius, Georg S
AU - Olbrich, Eckehard
ID - 1655
IS - 10
JF - Entropy
TI - Quantifying emergent behavior of autonomous robots
VL - 17
ER -
TY - CONF
AB - Recently there has been a significant effort to handle quantitative properties in formal verification and synthesis. While weighted automata over finite and infinite words provide a natural and flexible framework to express quantitative properties, perhaps surprisingly, some basic system properties such as average response time cannot be expressed using weighted automata, nor in any other know decidable formalism. In this work, we introduce nested weighted automata as a natural extension of weighted automata which makes it possible to express important quantitative properties such as average response time. In nested weighted automata, a master automaton spins off and collects results from weighted slave automata, each of which computes a quantity along a finite portion of an infinite word. Nested weighted automata can be viewed as the quantitative analogue of monitor automata, which are used in run-time verification. We establish an almost complete decidability picture for the basic decision problems about nested weighted automata, and illustrate their applicability in several domains. In particular, nested weighted automata can be used to decide average response time properties.
AU - Chatterjee, Krishnendu
AU - Henzinger, Thomas A
AU - Otop, Jan
ID - 1656
T2 - Proceedings - Symposium on Logic in Computer Science
TI - Nested weighted automata
VL - 2015-July
ER -
TY - CONF
AB - We consider Markov decision processes (MDPs) with multiple limit-average (or mean-payoff) objectives. There exist two different views: (i) ~the expectation semantics, where the goal is to optimize the expected mean-payoff objective, and (ii) ~the satisfaction semantics, where the goal is to maximize the probability of runs such that the mean-payoff value stays above a given vector. We consider optimization with respect to both objectives at once, thus unifying the existing semantics. Precisely, the goal is to optimize the expectation while ensuring the satisfaction constraint. Our problem captures the notion of optimization with respect to strategies that are risk-averse (i.e., Ensure certain probabilistic guarantee). Our main results are as follows: First, we present algorithms for the decision problems, which are always polynomial in the size of the MDP. We also show that an approximation of the Pareto curve can be computed in time polynomial in the size of the MDP, and the approximation factor, but exponential in the number of dimensions. Second, we present a complete characterization of the strategy complexity (in terms of memory bounds and randomization) required to solve our problem.
AU - Chatterjee, Krishnendu
AU - Komárková, Zuzana
AU - Kretinsky, Jan
ID - 1657
TI - Unifying two views on multiple mean-payoff objectives in Markov decision processes
ER -
TY - CONF
AB - Continuous-time Markov chain (CTMC) models have become a central tool for understanding the dynamics of complex reaction networks and the importance of stochasticity in the underlying biochemical processes. When such models are employed to answer questions in applications, in order to ensure that the model provides a sufficiently accurate representation of the real system, it is of vital importance that the model parameters are inferred from real measured data. This, however, is often a formidable task and all of the existing methods fail in one case or the other, usually because the underlying CTMC model is high-dimensional and computationally difficult to analyze. The parameter inference methods that tend to scale best in the dimension of the CTMC are based on so-called moment closure approximations. However, there exists a large number of different moment closure approximations and it is typically hard to say a priori which of the approximations is the most suitable for the inference procedure. Here, we propose a moment-based parameter inference method that automatically chooses the most appropriate moment closure method. Accordingly, contrary to existing methods, the user is not required to be experienced in moment closure techniques. In addition to that, our method adaptively changes the approximation during the parameter inference to ensure that always the best approximation is used, even in cases where different approximations are best in different regions of the parameter space.
AU - Bogomolov, Sergiy
AU - Henzinger, Thomas A
AU - Podelski, Andreas
AU - Ruess, Jakob
AU - Schilling, Christian
ID - 1658
TI - Adaptive moment closure for parameter inference of biochemical reaction networks
VL - 9308
ER -
TY - CONF
AB - The target discounted-sum problem is the following: Given a rational discount factor 0 < λ < 1 and three rational values a, b, and t, does there exist a finite or an infinite sequence w ε(a, b)∗ or w ε(a, b)w, such that Σ|w| i=0 w(i)λi equals t? The problem turns out to relate to many fields of mathematics and computer science, and its decidability question is surprisingly hard to solve. We solve the finite version of the problem, and show the hardness of the infinite version, linking it to various areas and open problems in mathematics and computer science: β-expansions, discounted-sum automata, piecewise affine maps, and generalizations of the Cantor set. We provide some partial results to the infinite version, among which are solutions to its restriction to eventually-periodic sequences and to the cases that λ λ 1/2 or λ = 1/n, for every n ε N. We use our results for solving some open problems on discounted-sum automata, among which are the exact-value problem for nondeterministic automata over finite words and the universality and inclusion problems for functional automata.
AU - Boker, Udi
AU - Henzinger, Thomas A
AU - Otop, Jan
ID - 1659
SN - 1043-6871
T2 - LICS
TI - The target discounted-sum problem
ER -
TY - CONF
AB - We study the pattern frequency vector for runs in probabilistic Vector Addition Systems with States (pVASS). Intuitively, each configuration of a given pVASS is assigned one of finitely many patterns, and every run can thus be seen as an infinite sequence of these patterns. The pattern frequency vector assigns to each run the limit of pattern frequencies computed for longer and longer prefixes of the run. If the limit does not exist, then the vector is undefined. We show that for one-counter pVASS, the pattern frequency vector is defined and takes one of finitely many values for almost all runs. Further, these values and their associated probabilities can be approximated up to an arbitrarily small relative error in polynomial time. For stable two-counter pVASS, we show the same result, but we do not provide any upper complexity bound. As a byproduct of our study, we discover counterexamples falsifying some classical results about stochastic Petri nets published in the 80s.
AU - Brázdil, Tomáš
AU - Kiefer, Stefan
AU - Kučera, Antonín
AU - Novotny, Petr
ID - 1660
TI - Long-run average behaviour of probabilistic vector addition systems
ER -
TY - CONF
AB - The computation of the winning set for one-pair Streett objectives and for k-pair Streett objectives in (standard) graphs as well as in game graphs are central problems in computer-aided verification, with application to the verification of closed systems with strong fairness conditions, the verification of open systems, checking interface compatibility, well-formed ness of specifications, and the synthesis of reactive systems. We give faster algorithms for the computation of the winning set for (1) one-pair Streett objectives (aka parity-3 problem) in game graphs and (2) for k-pair Streett objectives in graphs. For both problems this represents the first improvement in asymptotic running time in 15 years.
AU - Chatterjee, Krishnendu
AU - Henzinger, Monika
AU - Loitzenbauer, Veronika
ID - 1661
T2 - Proceedings - Symposium on Logic in Computer Science
TI - Improved algorithms for one-pair and k-pair Streett objectives
VL - 2015-July
ER -
TY - JOUR
AB - CREB-binding protein (CBP) and p300 are transcriptional coactivators involved in numerous biological processes that affect cell growth, transformation, differentiation, and development. In this study, we provide evidence of the involvement of homeodomain-interacting protein kinase 2 (HIPK2) in the regulation of CBP activity. We show that HIPK2 interacts with and phosphorylates several regions of CBP. We demonstrate that serines 2361, 2363, 2371, 2376, and 2381 are responsible for the HIPK2-induced mobility shift of CBP C-terminal activation domain. Moreover, we show that HIPK2 strongly potentiates the transcriptional activity of CBP. However, our data suggest that HIPK2 activates CBP mainly by counteracting the repressive action of cell cycle regulatory domain 1 (CRD1), located between amino acids 977 and 1076, independently of CBP phosphorylation. Our findings thus highlight a complex regulation of CBP activity by HIPK2, which might be relevant for the control of specific sets of target genes involved in cellular proliferation, differentiation and apoptosis.
AU - Kovács, Krisztián
AU - Steinmann, Myriam
AU - Halfon, Olivier
AU - Magistretti, Pierre
AU - Cardinaux, Jean
ID - 1663
IS - 11
JF - Cellular Signalling
TI - Complex regulation of CREB-binding protein by homeodomain-interacting protein kinase 2
VL - 27
ER -
TY - JOUR
AB - Over a century of research into the origin of turbulence in wall-bounded shear flows has resulted in a puzzling picture in which turbulence appears in a variety of different states competing with laminar background flow. At moderate flow speeds, turbulence is confined to localized patches; it is only at higher speeds that the entire flow becomes turbulent. The origin of the different states encountered during this transition, the front dynamics of the turbulent regions and the transformation to full turbulence have yet to be explained. By combining experiments, theory and computer simulations, here we uncover a bifurcation scenario that explains the transformation to fully turbulent pipe flow and describe the front dynamics of the different states encountered in the process. Key to resolving this problem is the interpretation of the flow as a bistable system with nonlinear propagation (advection) of turbulent fronts. These findings bridge the gap between our understanding of the onset of turbulence and fully turbulent flows.
AU - Barkley, Dwight
AU - Song, Baofang
AU - Vasudevan, Mukund
AU - Lemoult, Grégoire M
AU - Avila, Marc
AU - Hof, Björn
ID - 1664
IS - 7574
JF - Nature
TI - The rise of fully turbulent flow
VL - 526
ER -
TY - JOUR
AB - Which genetic alterations drive tumorigenesis and how they evolve over the course of disease and therapy are central questions in cancer biology. Here we identify 44 recurrently mutated genes and 11 recurrent somatic copy number variations through whole-exome sequencing of 538 chronic lymphocytic leukaemia (CLL) and matched germline DNA samples, 278 of which were collected in a prospective clinical trial. These include previously unrecognized putative cancer drivers (RPS15, IKZF3), and collectively identify RNA processing and export, MYC activity, and MAPK signalling as central pathways involved in CLL. Clonality analysis of this large data set further enabled reconstruction of temporal relationships between driver events. Direct comparison between matched pre-treatment and relapse samples from 59 patients demonstrated highly frequent clonal evolution. Thus, large sequencing data sets of clinically informative samples enable the discovery of novel genes associated with cancer, the network of relationships between the driver events, and their impact on disease relapse and clinical outcome.
AU - Landau, Dan
AU - Tausch, Eugen
AU - Taylor Weiner, Amaro
AU - Stewart, Chip
AU - Reiter, Johannes
AU - Bahlo, Jasmin
AU - Kluth, Sandra
AU - Božić, Ivana
AU - Lawrence, Michael
AU - Böttcher, Sebastian
AU - Carter, Scott
AU - Cibulskis, Kristian
AU - Mertens, Daniel
AU - Sougnez, Carrie
AU - Rosenberg, Mara
AU - Hess, Julian
AU - Edelmann, Jennifer
AU - Kless, Sabrina
AU - Kneba, Michael
AU - Ritgen, Matthias
AU - Fink, Anna
AU - Fischer, Kirsten
AU - Gabriel, Stacey
AU - Lander, Eric
AU - Nowak, Martin
AU - Döhner, Hartmut
AU - Hallek, Michael
AU - Neuberg, Donna
AU - Getz, Gad
AU - Stilgenbauer, Stephan
AU - Wu, Catherine
ID - 1665
IS - 7574
JF - Nature
TI - Mutations driving CLL and their evolution in progression and relapse
VL - 526
ER -