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 - 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 - 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
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 - 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 - 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 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 - 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 - 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 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
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 - 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 - CONF
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
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 - 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 - The synthesis problem asks for the automatic construction of a system from its specification. In the traditional setting, the system is “constructed from scratch” rather than composed from reusable components. However, this is rare in practice, and almost every non-trivial software system relies heavily on the use of libraries of reusable components. Recently, Lustig and Vardi introduced dataflow and controlflow synthesis from libraries of reusable components. They proved that dataflow synthesis is undecidable, while controlflow synthesis is decidable. The problem of controlflow synthesis from libraries of probabilistic components was considered by Nain, Lustig and Vardi, and was shown to be decidable for qualitative analysis (that asks that the specification be satisfied with probability 1). Our main contribution for controlflow synthesis from probabilistic components is to establish better complexity bounds for the qualitative analysis problem, and to show that the more general quantitative problem is undecidable. For the qualitative analysis, we show that the problem (i) is EXPTIME-complete when the specification is given as a deterministic parity word automaton, improving the previously known 2EXPTIME upper bound; and (ii) belongs to UP ∩ coUP and is parity-games hard, when the specification is given directly as a parity condition on the components, improving the previously known EXPTIME upper bound.
AU - Chatterjee, Krishnendu
AU - Doyen, Laurent
AU - Vardi, Moshe
ID - 1609
TI - The complexity of synthesis from probabilistic components
VL - 9135
ER -
TY - 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 - We propose a method for fabricating deformable objects with spatially varying elasticity using 3D printing. Using a single, relatively stiff printer material, our method designs an assembly of smallscale microstructures that have the effect of a softer material at the object scale, with properties depending on the microstructure used in each part of the object. We build on work in the area of metamaterials, using numerical optimization to design tiled microstructures with desired properties, but with the key difference that our method designs families of related structures that can be interpolated to smoothly vary the material properties over a wide range. To create an object with spatially varying elastic properties, we tile the object's interior with microstructures drawn from these families, generating a different microstructure for each cell using an efficient algorithm to select compatible structures for neighboring cells. We show results computed for both 2D and 3D objects, validating several 2D and 3D printed structures using standard material tests as well as demonstrating various example applications.
AU - Schumacher, Christian
AU - Bickel, Bernd
AU - Rys, Jan
AU - Marschner, Steve
AU - Daraio, Chiara
AU - Gross, Markus
ID - 1628
IS - 4
TI - Microstructures to control elasticity in 3D printing
VL - 34
ER -
TY - CONF
AB - We present a method to learn and propagate shape placements in 2D polygonal scenes from a few examples provided by a user. The placement of a shape is modeled as an oriented bounding box. Simple geometric relationships between this bounding box and nearby scene polygons define a feature set for the placement. The feature sets of all example placements are then used to learn a probabilistic model over all possible placements and scenes. With this model, we can generate a new set of placements with similar geometric relationships in any given scene. We introduce extensions that enable propagation and generation of shapes in 3D scenes, as well as the application of a learned modeling session to large scenes without additional user interaction. These concepts allow us to generate complex scenes with thousands of objects with relatively little user interaction.
AU - Guerrero, Paul
AU - Jeschke, Stefan
AU - Wimmer, Michael
AU - Wonka, Peter
ID - 1630
IS - 4
TI - Learning shape placements by example
VL - 34
ER -
TY - CONF
AB - This paper presents a liquid simulation technique that enforces the incompressibility condition using a stream function solve instead of a pressure projection. Previous methods have used stream function techniques for the simulation of detailed single-phase flows, but a formulation for liquid simulation has proved elusive in part due to the free surface boundary conditions. In this paper, we introduce a stream function approach to liquid simulations with novel boundary conditions for free surfaces, solid obstacles, and solid-fluid coupling.
Although our approach increases the dimension of the linear system necessary to enforce incompressibility, it provides interesting and surprising benefits. First, the resulting flow is guaranteed to be divergence-free regardless of the accuracy of the solve. Second, our free-surface boundary conditions guarantee divergence-free motion even in the un-simulated air phase, which enables two-phase flow simulation by only computing a single phase. We implemented this method using a variant of FLIP simulation which only samples particles within a narrow band of the liquid surface, and we illustrate the effectiveness of our method for detailed two-phase flow simulations with complex boundaries, detailed bubble interactions, and two-way solid-fluid coupling.
AU - Ando, Ryoichi
AU - Thuerey, Nils
AU - Wojtan, Christopher J
ID - 1632
IS - 4
TI - A stream function solver for liquid simulations
VL - 34
ER -
TY - CONF
AB - We present a method for simulating brittle fracture under the assumptions of quasi-static linear elastic fracture mechanics (LEFM). Using the boundary element method (BEM) and Lagrangian crack-fronts, we produce highly detailed fracture surfaces. The computational cost of the BEM is alleviated by using a low-resolution mesh and interpolating the resulting stress intensity factors when propagating the high-resolution crack-front.
Our system produces physics-based fracture surfaces with high spatial and temporal resolution, taking spatial variation of material toughness and/or strength into account. It also allows for crack initiation to be handled separately from crack propagation, which is not only more reasonable from a physics perspective, but can also be used to control the simulation.
Separating the resolution of the crack-front from the resolution of the computational mesh increases the efficiency and therefore the amount of visual detail on the resulting fracture surfaces. The BEM also allows us to re-use previously computed blocks of the system matrix.
AU - Hahn, David
AU - Wojtan, Christopher J
ID - 1633
IS - 4
TI - High-resolution brittle fracture simulation with boundary elements
VL - 34
ER -
TY - CONF
AB - Simulating the delightful dynamics of soap films, bubbles, and foams has traditionally required the use of a fully three-dimensional many-phase Navier-Stokes solver, even though their visual appearance is completely dominated by the thin liquid surface. We depart from earlier work on soap bubbles and foams by noting that their dynamics are naturally described by a Lagrangian vortex sheet model in which circulation is the primary variable. This leads us to derive a novel circulation-preserving surface-only discretization of foam dynamics driven by surface tension on a non-manifold triangle mesh. We represent the surface using a mesh-based multimaterial surface tracker which supports complex bubble topology changes, and evolve the surface according to the ambient air flow induced by a scalar circulation field stored on the mesh. Surface tension forces give rise to a simple update rule for circulation, even at non-manifold Plateau borders, based on a discrete measure of signed scalar mean curvature. We further incorporate vertex constraints to enable the interaction of soap films with wires. The result is a method that is at once simple, robust, and efficient, yet able to capture an array of soap films behaviors including foam rearrangement, catenoid collapse, blowing bubbles, and double bubbles being pulled apart.
AU - Da, Fang
AU - Batty, Christopher
AU - Wojtan, Christopher J
AU - Grinspun, Eitan
ID - 1634
IS - 4
TI - Double bubbles sans toil and trouble: discrete circulation-preserving vortex sheets for soap films and foams
VL - 34
ER -
TY - JOUR
AB - We calculate a Ricci curvature lower bound for some classical examples of random walks, namely, a chain on a slice of the n-dimensional discrete cube (the so-called Bernoulli-Laplace model) and the random transposition shuffle of the symmetric group of permutations on n letters.
AU - Erbar, Matthias
AU - Maas, Jan
AU - Tetali, Prasad
ID - 1635
IS - 4
JF - Annales de la faculté des sciences de Toulouse
TI - Discrete Ricci curvature bounds for Bernoulli-Laplace and random transposition models
VL - 24
ER -
TY - CONF
AB - Constraint Satisfaction Problem (CSP) is a fundamental algorithmic problem that appears in many areas of Computer Science. It can be equivalently stated as computing a homomorphism R→ΓΓ between two relational structures, e.g. between two directed graphs. Analyzing its complexity has been a prominent research direction, especially for the fixed template CSPs where the right side ΓΓ is fixed and the left side R is unconstrained.
Far fewer results are known for the hybrid setting that restricts both sides simultaneously. It assumes that R belongs to a certain class of relational structures (called a structural restriction in this paper). We study which structural restrictions are effective, i.e. there exists a fixed template ΓΓ (from a certain class of languages) for which the problem is tractable when R is restricted, and NP-hard otherwise. We provide a characterization for structural restrictions that are closed under inverse homomorphisms. The criterion is based on the chromatic number of a relational structure defined in this paper; it generalizes the standard chromatic number of a graph.
As our main tool, we use the algebraic machinery developed for fixed template CSPs. To apply it to our case, we introduce a new construction called a “lifted language”. We also give a characterization for structural restrictions corresponding to minor-closed families of graphs, extend results to certain Valued CSPs (namely conservative valued languages), and state implications for (valued) CSPs with ordered variables and for the maximum weight independent set problem on some restricted families of graphs.
AU - Kolmogorov, Vladimir
AU - Rolinek, Michal
AU - Takhanov, Rustem
ID - 1636
TI - Effectiveness of structural restrictions for hybrid CSPs
VL - 9472
ER -
TY - CONF
AB - An instance of the Valued Constraint Satisfaction Problem (VCSP) is given by a finite set of variables, a finite domain of labels, and a sum of functions, each function depending on a subset of the variables. Each function can take finite values specifying costs of assignments of labels to its variables or the infinite value, which indicates an infeasible assignment. The goal is to find an assignment of labels to the variables that minimizes the sum. We study, assuming that P ≠ NP, how the complexity of this very general problem depends on the set of functions allowed in the instances, the so-called constraint language. The case when all allowed functions take values in {0, ∞} corresponds to ordinary CSPs, where one deals only with the feasibility issue and there is no optimization. This case is the subject of the Algebraic CSP Dichotomy Conjecture predicting for which constraint languages CSPs are tractable (i.e. solvable in polynomial time) and for which NP-hard. The case when all allowed functions take only finite values corresponds to finite-valued CSP, where the feasibility aspect is trivial and one deals only with the optimization issue. The complexity of finite-valued CSPs was fully classified by Thapper and Zivny. An algebraic necessary condition for tractability of a general-valued CSP with a fixed constraint language was recently given by Kozik and Ochremiak. As our main result, we prove that if a constraint language satisfies this algebraic necessary condition, and the feasibility CSP (i.e. the problem of deciding whether a given instance has a feasible solution) corresponding to the VCSP with this language is tractable, then the VCSP is tractable. The algorithm is a simple combination of the assumed algorithm for the feasibility CSP and the standard LP relaxation. As a corollary, we obtain that a dichotomy for ordinary CSPs would imply a dichotomy for general-valued CSPs.
AU - Kolmogorov, Vladimir
AU - Krokhin, Andrei
AU - Rolinek, Michal
ID - 1637
TI - The complexity of general-valued CSPs
ER -
TY - JOUR
AB - 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 - A pseudorandom function (PRF) is a keyed function F : K × X → Y where, for a random key k ∈ K, the function F(k, ·) is indistinguishable from a uniformly random function, given black-box access. A key-homomorphic PRF has the additional feature that for any keys k, k' and any input x, we have F(k+k', x) = F(k, x)⊕F(k', x) for some group operations +,⊕ on K and Y, respectively. A constrained PRF for a family of setsS ⊆ P(X) has the property that, given any key k and set S ∈ S, one can efficiently compute a “constrained” key kS that enables evaluation of F(k, x) on all inputs x ∈ S, while the values F(k, x) for x /∈ S remain pseudorandom even given kS. In this paper we construct PRFs that are simultaneously constrained and key homomorphic, where the homomorphic property holds even for constrained keys. We first show that the multilinear map-based bit-fixing and circuit-constrained PRFs of Boneh and Waters (Asiacrypt 2013) can be modified to also be keyhomomorphic. We then show that the LWE-based key-homomorphic PRFs of Banerjee and Peikert (Crypto 2014) are essentially already prefix-constrained PRFs, using a (non-obvious) definition of constrained keys and associated group operation. Moreover, the constrained keys themselves are pseudorandom, and the constraining and evaluation functions can all be computed in low depth. As an application of key-homomorphic constrained PRFs,we construct a proxy re-encryption schemewith fine-grained access control. This scheme allows storing encrypted data on an untrusted server, where each file can be encrypted relative to some attributes, so that only parties whose constrained keys match the attributes can decrypt. Moreover, the server can re-key (arbitrary subsets of) the ciphertexts without learning anything about the plaintexts, thus permitting efficient and finegrained revocation.
AU - Banerjee, Abishek
AU - Fuchsbauer, Georg
AU - Peikert, Chris
AU - Pietrzak, Krzysztof Z
AU - Stevens, Sophie
ID - 1646
TI - Key-homomorphic constrained pseudorandom functions
VL - 9015
ER -
TY - CONF
AB - Round-optimal blind signatures are notoriously hard to construct in the standard model, especially in the malicious-signer model, where blindness must hold under adversarially chosen keys. This is substantiated by several impossibility results. The only construction that can be termed theoretically efficient, by Garg and Gupta (Eurocrypt’14), requires complexity leveraging, inducing an exponential security loss. We present a construction of practically efficient round-optimal blind signatures in the standard model. It is conceptually simple and builds on the recent structure-preserving signatures on equivalence classes (SPSEQ) from Asiacrypt’14. While the traditional notion of blindness follows from standard assumptions, we prove blindness under adversarially chosen keys under an interactive variant of DDH. However, we neither require non-uniform assumptions nor complexity leveraging. We then show how to extend our construction to partially blind signatures and to blind signatures on message vectors, which yield a construction of one-show anonymous credentials à la “anonymous credentials light” (CCS’13) in the standard model. Furthermore, we give the first SPS-EQ construction under noninteractive assumptions and show how SPS-EQ schemes imply conventional structure-preserving signatures, which allows us to apply optimality results for the latter to SPS-EQ.
AU - Fuchsbauer, Georg
AU - Hanser, Christian
AU - Slamanig, Daniel
ID - 1647
TI - Practical round-optimal blind signatures in the standard model
VL - 9216
ER -
TY - CONF
AB - Generalized Selective Decryption (GSD), introduced by Panjwani [TCC’07], is a game for a symmetric encryption scheme Enc that captures the difficulty of proving adaptive security of certain protocols, most notably the Logical Key Hierarchy (LKH) multicast encryption protocol. In the GSD game there are n keys k1,..., kn, which the adversary may adaptively corrupt (learn); moreover, it can ask for encryptions Encki (kj) of keys under other keys. The adversary’s task is to distinguish keys (which it cannot trivially compute) from random. Proving the hardness of GSD assuming only IND-CPA security of Enc is surprisingly hard. Using “complexity leveraging” loses a factor exponential in n, which makes the proof practically meaningless. We can think of the GSD game as building a graph on n vertices, where we add an edge i → j when the adversary asks for an encryption of kj under ki. If restricted to graphs of depth ℓ, Panjwani gave a reduction that loses only a factor exponential in ℓ (not n). To date, this is the only non-trivial result known for GSD. In this paper we give almost-polynomial reductions for large classes of graphs. Most importantly, we prove the security of the GSD game restricted to trees losing only a quasi-polynomial factor n3 log n+5. Trees are an important special case capturing real-world protocols like the LKH protocol. Our new bound improves upon Panjwani’s on some LKH variants proposed in the literature where the underlying tree is not balanced. Our proof builds on ideas from the “nested hybrids” technique recently introduced by Fuchsbauer et al. [Asiacrypt’14] for proving the adaptive security of constrained PRFs.
AU - Fuchsbauer, Georg
AU - Jafargholi, Zahra
AU - Pietrzak, Krzysztof Z
ID - 1648
TI - A quasipolynomial reduction for generalized selective decryption on trees
VL - 9215
ER -
TY - CONF
AB - We extend a commitment scheme based on the learning with errors over rings (RLWE) problem, and present efficient companion zeroknowledge proofs of knowledge. Our scheme maps elements from the ring (or equivalently, n elements from
AU - Benhamouda, Fabrice
AU - Krenn, Stephan
AU - Lyubashevsky, Vadim
AU - Pietrzak, Krzysztof Z
ID - 1649
TI - Efficient zero-knowledge proofs for commitments from learning with errors over rings
VL - 9326
ER -
TY - CONF
AB - We consider the task of deriving a key with high HILL entropy (i.e., being computationally indistinguishable from a key with high min-entropy) from an unpredictable source.
Previous to this work, the only known way to transform unpredictability into a key that was ϵ indistinguishable from having min-entropy was via pseudorandomness, for example by Goldreich-Levin (GL) hardcore bits. This approach has the inherent limitation that from a source with k bits of unpredictability entropy one can derive a key of length (and thus HILL entropy) at most k−2log(1/ϵ) bits. In many settings, e.g. when dealing with biometric data, such a 2log(1/ϵ) bit entropy loss in not an option. Our main technical contribution is a theorem that states that in the high entropy regime, unpredictability implies HILL entropy. Concretely, any variable K with |K|−d bits of unpredictability entropy has the same amount of so called metric entropy (against real-valued, deterministic distinguishers), which is known to imply the same amount of HILL entropy. The loss in circuit size in this argument is exponential in the entropy gap d, and thus this result only applies for small d (i.e., where the size of distinguishers considered is exponential in d).
To overcome the above restriction, we investigate if it’s possible to first “condense” unpredictability entropy and make the entropy gap small. We show that any source with k bits of unpredictability can be condensed into a source of length k with k−3 bits of unpredictability entropy. Our condenser simply “abuses" the GL construction and derives a k bit key from a source with k bits of unpredicatibily. The original GL theorem implies nothing when extracting that many bits, but we show that in this regime, GL still behaves like a “condenser" for unpredictability. This result comes with two caveats (1) the loss in circuit size is exponential in k and (2) we require that the source we start with has no HILL entropy (equivalently, one can efficiently check if a guess is correct). We leave it as an intriguing open problem to overcome these restrictions or to prove they’re inherent.
AU - Skórski, Maciej
AU - Golovnev, Alexander
AU - Pietrzak, Krzysztof Z
ID - 1650
TI - Condensed unpredictability
VL - 9134
ER -
TY - CONF
AB - 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 - 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 - Over a century of research into the origin of turbulence in wall-bounded shear flows has resulted in a puzzling picture in which turbulence appears in a variety of different states competing with laminar background flow. At moderate flow speeds, turbulence is confined to localized patches; it is only at higher speeds that the entire flow becomes turbulent. The origin of the different states encountered during this transition, the front dynamics of the turbulent regions and the transformation to full turbulence have yet to be explained. By combining experiments, theory and computer simulations, here we uncover a bifurcation scenario that explains the transformation to fully turbulent pipe flow and describe the front dynamics of the different states encountered in the process. Key to resolving this problem is the interpretation of the flow as a bistable system with nonlinear propagation (advection) of turbulent fronts. These findings bridge the gap between our understanding of the onset of turbulence and fully turbulent flows.
AU - Barkley, Dwight
AU - Song, Baofang
AU - Vasudevan, Mukund
AU - Lemoult, Grégoire M
AU - Avila, Marc
AU - Hof, Björn
ID - 1664
IS - 7574
JF - Nature
TI - The rise of fully turbulent flow
VL - 526
ER -
TY - JOUR
AB - Which genetic alterations drive tumorigenesis and how they evolve over the course of disease and therapy are central questions in cancer biology. Here we identify 44 recurrently mutated genes and 11 recurrent somatic copy number variations through whole-exome sequencing of 538 chronic lymphocytic leukaemia (CLL) and matched germline DNA samples, 278 of which were collected in a prospective clinical trial. These include previously unrecognized putative cancer drivers (RPS15, IKZF3), and collectively identify RNA processing and export, MYC activity, and MAPK signalling as central pathways involved in CLL. Clonality analysis of this large data set further enabled reconstruction of temporal relationships between driver events. Direct comparison between matched pre-treatment and relapse samples from 59 patients demonstrated highly frequent clonal evolution. Thus, large sequencing data sets of clinically informative samples enable the discovery of novel genes associated with cancer, the network of relationships between the driver events, and their impact on disease relapse and clinical outcome.
AU - Landau, Dan
AU - Tausch, Eugen
AU - Taylor Weiner, Amaro
AU - Stewart, Chip
AU - Reiter, Johannes
AU - Bahlo, Jasmin
AU - Kluth, Sandra
AU - Božić, Ivana
AU - Lawrence, Michael
AU - Böttcher, Sebastian
AU - Carter, Scott
AU - Cibulskis, Kristian
AU - Mertens, Daniel
AU - Sougnez, Carrie
AU - Rosenberg, Mara
AU - Hess, Julian
AU - Edelmann, Jennifer
AU - Kless, Sabrina
AU - Kneba, Michael
AU - Ritgen, Matthias
AU - Fink, Anna
AU - Fischer, Kirsten
AU - Gabriel, Stacey
AU - Lander, Eric
AU - Nowak, Martin
AU - Döhner, Hartmut
AU - Hallek, Michael
AU - Neuberg, Donna
AU - Getz, Gad
AU - Stilgenbauer, Stephan
AU - Wu, Catherine
ID - 1665
IS - 7574
JF - Nature
TI - Mutations driving CLL and their evolution in progression and relapse
VL - 526
ER -
TY - CONF
AB - We consider parametric version of fixed-delay continuoustime Markov chains (or equivalently deterministic and stochastic Petri nets, DSPN) where fixed-delay transitions are specified by parameters, rather than concrete values. Our goal is to synthesize values of these parameters that, for a given cost function, minimise expected total cost incurred before reaching a given set of target states. We show that under mild assumptions, optimal values of parameters can be effectively approximated using translation to a Markov decision process (MDP) whose actions correspond to discretized values of these parameters. To this end we identify and overcome several interesting phenomena arising in systems with fixed delays.
AU - Brázdil, Tomáš
AU - Korenčiak, L'Uboš
AU - Krčál, Jan
AU - Novotny, Petr
AU - Řehák, Vojtěch
ID - 1667
TI - Optimizing performance of continuous-time stochastic systems using timeout synthesis
VL - 9259
ER -
TY - CONF
AB - We revisit the security (as a pseudorandom permutation) of cascading-based constructions for block-cipher key-length extension. Previous works typically considered the extreme case where the adversary is given the entire codebook of the construction, the only complexity measure being the number qe of queries to the underlying ideal block cipher, representing adversary’s secret-key-independent computation. Here, we initiate a systematic study of the more natural case of an adversary restricted to adaptively learning a number qc of plaintext/ciphertext pairs that is less than the entire codebook. For any such qc, we aim to determine the highest number of block-cipher queries qe the adversary can issue without being able to successfully distinguish the construction (under a secret key) from a random permutation.
More concretely, we show the following results for key-length extension schemes using a block cipher with n-bit blocks and κ-bit keys:
Plain cascades of length ℓ=2r+1 are secure whenever qcqre≪2r(κ+n), qc≪2κ and qe≪22κ. The bound for r=1 also applies to two-key triple encryption (as used within Triple DES).
The r-round XOR-cascade is secure as long as qcqre≪2r(κ+n), matching an attack by Gaži (CRYPTO 2013).
We fully characterize the security of Gaži and Tessaro’s two-call
AU - Gazi, Peter
AU - Lee, Jooyoung
AU - Seurin, Yannick
AU - Steinberger, John
AU - Tessaro, Stefano
ID - 1668
TI - Relaxing full-codebook security: A refined analysis of key-length extension schemes
VL - 9054
ER -
TY - CONF
AB - Computational notions of entropy (a.k.a. pseudoentropy) have found many applications, including leakage-resilient cryptography, deterministic encryption or memory delegation. The most important tools to argue about pseudoentropy are chain rules, which quantify by how much (in terms of quantity and quality) the pseudoentropy of a given random variable X decreases when conditioned on some other variable Z (think for example of X as a secret key and Z as information leaked by a side-channel). In this paper we give a very simple and modular proof of the chain rule for HILL pseudoentropy, improving best known parameters. Our version allows for increasing the acceptable length of leakage in applications up to a constant factor compared to the best previous bounds. As a contribution of independent interest, we provide a comprehensive study of all known versions of the chain rule, comparing their worst-case strength and limitations.
AU - Pietrzak, Krzysztof Z
AU - Skórski, Maciej
ID - 1669
TI - The chain rule for HILL pseudoentropy, revisited
VL - 9230
ER -
TY - CONF
AB - This paper studies the concrete security of PRFs and MACs obtained by keying hash functions based on the sponge paradigm. One such hash function is KECCAK, selected as NIST’s new SHA-3 standard. In contrast to other approaches like HMAC, the exact security of keyed sponges is not well understood. Indeed, recent security analyses delivered concrete security bounds which are far from existing attacks. This paper aims to close this gap. We prove (nearly) exact bounds on the concrete PRF security of keyed sponges using a random permutation. These bounds are tight for the most relevant ranges of parameters, i.e., for messages of length (roughly) l ≤ min{2n/4, 2r} blocks, where n is the state size and r is the desired output length; and for l ≤ q queries (to the construction or the underlying permutation). Moreover, we also improve standard-model bounds. As an intermediate step of independent interest, we prove tight bounds on the PRF security of the truncated CBC-MAC construction, which operates as plain CBC-MAC, but only returns a prefix of the output.
AU - Gazi, Peter
AU - Pietrzak, Krzysztof Z
AU - Tessaro, Stefano
ID - 1671
TI - The exact PRF security of truncation: Tight bounds for keyed sponges and truncated CBC
VL - 9215
ER -
TY - CONF
AB - Composable notions of incoercibility aim to forbid a coercer from using anything beyond the coerced parties’ inputs and outputs to catch them when they try to deceive him. Existing definitions are restricted to weak coercion types, and/or are not universally composable. Furthermore, they often make too strong assumptions on the knowledge of coerced parties—e.g., they assume they known the identities and/or the strategies of other coerced parties, or those of corrupted parties— which makes them unsuitable for applications of incoercibility such as e-voting, where colluding adversarial parties may attempt to coerce honest voters, e.g., by offering them money for a promised vote, and use their own view to check that the voter keeps his end of the bargain. In this work we put forward the first universally composable notion of incoercible multi-party computation, which satisfies the above intuition and does not assume collusions among coerced parties or knowledge of the corrupted set. We define natural notions of UC incoercibility corresponding to standard coercion-types, i.e., receipt-freeness and resistance to full-active coercion. Importantly, our suggested notion has the unique property that it builds on top of the well studied UC framework by Canetti instead of modifying it. This guarantees backwards compatibility, and allows us to inherit results from the rich UC literature. We then present MPC protocols which realize our notions of UC incoercibility given access to an arguably minimal setup—namely honestly generate tamper-proof hardware performing a very simple cryptographic operation—e.g., a smart card. This is, to our knowledge, the first proposed construction of an MPC protocol (for more than two parties) that is incoercibly secure and universally composable, and therefore the first construction of a universally composable receipt-free e-voting protocol.
AU - Alwen, Joel F
AU - Ostrovsky, Rafail
AU - Zhou, Hongsheng
AU - Zikas, Vassilis
ID - 1672
TI - Incoercible multi-party computation and universally composable receipt-free voting
VL - 9216
ER -
TY - JOUR
AB - When a new mutant arises in a population, there is a probability it outcompetes the residents and fixes. The structure of the population can affect this fixation probability. Suppressing population structures reduce the difference between two competing variants, while amplifying population structures enhance the difference. Suppressors are ubiquitous and easy to construct, but amplifiers for the large population limit are more elusive and only a few examples have been discovered. Whether or not a population structure is an amplifier of selection depends on the probability distribution for the placement of the invading mutant. First, we prove that there exist only bounded amplifiers for adversarial placement-that is, for arbitrary initial conditions. Next, we show that the Star population structure, which is known to amplify for mutants placed uniformly at random, does not amplify for mutants that arise through reproduction and are therefore placed proportional to the temperatures of the vertices. Finally, we construct population structures that amplify for all mutational events that arise through reproduction, uniformly at random, or through some combination of the two.
AU - Adlam, Ben
AU - Chatterjee, Krishnendu
AU - Nowak, Martin
ID - 1673
IS - 2181
JF - Proceedings of the Royal Society A: Mathematical, Physical and Engineering Sciences
TI - Amplifiers of selection
VL - 471
ER -
TY - JOUR
AB - We consider N × N random matrices of the form H = W + V where W is a real symmetric Wigner matrix and V a random or deterministic, real, diagonal matrix whose entries are independent of W. We assume subexponential decay for the matrix entries of W and we choose V so that the eigenvalues of W and V are typically of the same order. For a large class of diagonal matrices V, we show that the rescaled distribution of the extremal eigenvalues is given by the Tracy-Widom distribution F1 in the limit of large N. Our proofs also apply to the complex Hermitian setting, i.e. when W is a complex Hermitian Wigner matrix.
AU - Lee, Jioon
AU - Schnelli, Kevin
ID - 1674
IS - 8
JF - Reviews in Mathematical Physics
TI - Edge universality for deformed Wigner matrices
VL - 27
ER -
TY - JOUR
AB - We consider real symmetric and complex Hermitian random matrices with the additional symmetry hxy = hN-y,N-x. The matrix elements are independent (up to the fourfold symmetry) and not necessarily identically distributed. This ensemble naturally arises as the Fourier transform of a Gaussian orthogonal ensemble. Italso occurs as the flip matrix model - an approximation of the two-dimensional Anderson model at small disorder. We show that the density of states converges to the Wigner semicircle law despite the new symmetry type. We also prove the local version of the semicircle law on the optimal scale.
AU - Alt, Johannes
ID - 1677
IS - 10
JF - Journal of Mathematical Physics
TI - The local semicircle law for random matrices with a fourfold symmetry
VL - 56
ER -
TY - JOUR
AB - High-throughput live-cell screens are intricate elements of systems biology studies and drug discovery pipelines. Here, we demonstrate an optogenetics-assisted method that avoids the need for chemical activators and reporters, reduces the number of operational steps and increases information content in a cell-based small-molecule screen against human protein kinases, including an orphan receptor tyrosine kinase. This blueprint for all-optical screening can be adapted to many drug targets and cellular processes.
AU - Inglés Prieto, Álvaro
AU - Gschaider-Reichhart, Eva
AU - Muellner, Markus
AU - Nowak, Matthias
AU - Nijman, Sebastian
AU - Grusch, Michael
AU - Janovjak, Harald L
ID - 1678
IS - 12
JF - Nature Chemical Biology
TI - Light-assisted small-molecule screening against protein kinases
VL - 11
ER -
TY - JOUR
AU - Lemoult, Grégoire M
AU - Maier, Philipp
AU - Hof, Björn
ID - 1679
IS - 9
JF - Physics of Fluids
TI - Taylor's Forest
VL - 27
ER -
TY - JOUR
AB - In many social situations, individuals endeavor to find the single best possible partner, but are constrained to evaluate the candidates in sequence. Examples include the search for mates, economic partnerships, or any other long-term ties where the choice to interact involves two parties. Surprisingly, however, previous theoretical work on mutual choice problems focuses on finding equilibrium solutions, while ignoring the evolutionary dynamics of decisions. Empirically, this may be of high importance, as some equilibrium solutions can never be reached unless the population undergoes radical changes and a sufficient number of individuals change their decisions simultaneously. To address this question, we apply a mutual choice sequential search problem in an evolutionary game-theoretical model that allows one to find solutions that are favored by evolution. As an example, we study the influence of sequential search on the evolutionary dynamics of cooperation. For this, we focus on the classic snowdrift game and the prisoner’s dilemma game.
AU - Priklopil, Tadeas
AU - Chatterjee, Krishnendu
ID - 1681
IS - 4
JF - Games
TI - Evolution of decisions in population games with sequentially searching individuals
VL - 6
ER -
TY - JOUR
AB - We study the problem of robust satisfiability of systems of nonlinear equations, namely, whether for a given continuous function f:K→ ℝn on a finite simplicial complex K and α > 0, it holds that each function g: K → ℝn such that ||g - f || ∞ < α, has a root in K. Via a reduction to the extension problem of maps into a sphere, we particularly show that this problem is decidable in polynomial time for every fixed n, assuming dimK ≤ 2n - 3. This is a substantial extension of previous computational applications of topological degree and related concepts in numerical and interval analysis. Via a reverse reduction, we prove that the problem is undecidable when dim K > 2n - 2, where the threshold comes from the stable range in homotopy theory. For the lucidity of our exposition, we focus on the setting when f is simplexwise linear. Such functions can approximate general continuous functions, and thus we get approximation schemes and undecidability of the robust satisfiability in other possible settings.
AU - Franek, Peter
AU - Krcál, Marek
ID - 1682
IS - 4
JF - Journal of the ACM
TI - Robust satisfiability of systems of equations
VL - 62
ER -
TY - JOUR
AB - Many species groups, including mammals and many insects, determine sex using heteromorphic sex chromosomes. Diptera flies, which include the model Drosophila melanogaster, generally have XY sex chromosomes and a conserved karyotype consisting of six chromosomal arms (five large rods and a small dot), but superficially similar karyotypes may conceal the true extent of sex chromosome variation. Here, we use whole-genome analysis in 37 fly species belonging to 22 different families of Diptera and uncover tremendous hidden diversity in sex chromosome karyotypes among flies. We identify over a dozen different sex chromosome configurations, and the small dot chromosome is repeatedly used as the sex chromosome, which presumably reflects the ancestral karyotype of higher Diptera. However, we identify species with undifferentiated sex chromosomes, others in which a different chromosome replaced the dot as a sex chromosome or in which up to three chromosomal elements became incorporated into the sex chromosomes, and others yet with female heterogamety (ZW sex chromosomes). Transcriptome analysis shows that dosage compensation has evolved multiple times in flies, consistently through up-regulation of the single X in males. However, X chromosomes generally show a deficiency of genes with male-biased expression, possibly reflecting sex-specific selective pressures. These species thus provide a rich resource to study sex chromosome biology in a comparative manner and show that similar selective forces have shaped the unique evolution of sex chromosomes in diverse fly taxa.
AU - Vicoso, Beatriz
AU - Bachtrog, Doris
ID - 1684
IS - 4
JF - PLoS Biology
TI - Numerous transitions of sex chromosomes in Diptera
VL - 13
ER -
TY - CONF
AB - Given a graph G cellularly embedded on a surface Σ of genus g, a cut graph is a subgraph of G such that cutting Σ along G yields a topological disk. We provide a fixed parameter tractable approximation scheme for the problem of computing the shortest cut graph, that is, for any ε > 0, we show how to compute a (1 + ε) approximation of the shortest cut graph in time f(ε, g)n3.
Our techniques first rely on the computation of a spanner for the problem using the technique of brick decompositions, to reduce the problem to the case of bounded tree-width. Then, to solve the bounded tree-width case, we introduce a variant of the surface-cut decomposition of Rué, Sau and Thilikos, which may be of independent interest.
AU - Cohen Addad, Vincent
AU - De Mesmay, Arnaud N
ID - 1685
TI - A fixed parameter tractable approximation scheme for the optimal cut graph of a surface
VL - 9294
ER -
TY - JOUR
AB - We show that the simplest building blocks of origami-based materials - rigid, degree-four vertices - are generically multistable. The existence of two distinct branches of folding motion emerging from the flat state suggests at least bistability, but we show how nonlinearities in the folding motions allow generic vertex geometries to have as many as five stable states. In special geometries with collinear folds and symmetry, more branches emerge leading to as many as six stable states. Tuning the fold energy parameters, we show how monostability is also possible. Finally, we show how to program the stability features of a single vertex into a periodic fold tessellation. The resulting metasheets provide a previously unanticipated functionality - tunable and switchable shape and size via multistability.
AU - Waitukaitis, Scott R
AU - Menaut, Rémi
AU - Chen, Bryan
AU - Van Hecke, Martin
ID - 121
IS - 5
JF - APS Physics, Physical Review Letters
TI - Origami multistability: From single vertices to metasheets
VL - 114
ER -
TY - JOUR
AB - Motility is a basic feature of living microorganisms, and how it works is often determined by environmental cues. Recent efforts have focused on developing artificial systems that can mimic microorganisms, in particular their self-propulsion. We report on the design and characterization of synthetic self-propelled particles that migrate upstream, known as positive rheotaxis. This phenomenon results from a purely physical mechanism involving the interplay between the polarity of the particles and their alignment by a viscous torque. We show quantitative agreement between experimental data and a simple model of an overdamped Brownian pendulum. The model notably predicts the existence of a stagnation point in a diverging flow. We take advantage of this property to demonstrate that our active particles can sense and predictably organize in an imposed flow. Our colloidal system represents an important step toward the realization of biomimetic microsystems with the ability to sense and respond to environmental changes.
AU - Palacci, Jérémie A
AU - Sacanna, Stefano
AU - Abramian, Anaïs
AU - Barral, Jérémie
AU - Hanson, Kasey
AU - Grosberg, Alexander Y.
AU - Pine, David J.
AU - Chaikin, Paul M.
ID - 9057
IS - 4
JF - Science Advances
SN - 2375-2548
TI - Artificial rheotaxis
VL - 1
ER -
TY - JOUR
AB - The breaking of internal tides is believed to provide a large part of the power needed to mix the abyssal ocean and sustain the meridional overturning circulation. Both the fraction of internal tide energy that is dissipated locally and the resulting vertical mixing distribution are crucial for the ocean state, but remain poorly quantified. Here we present a first worldwide estimate of mixing due to internal tides generated at small‐scale abyssal hills. Our estimate is based on linear wave theory, a nonlinear parameterization for wave breaking and uses quasi‐global small‐scale abyssal hill bathymetry, stratification, and tidal data. We show that a large fraction of abyssal‐hill generated internal tide energy is locally dissipated over mid‐ocean ridges in the Southern Hemisphere. Significant dissipation occurs above ridge crests, and, upon rescaling by the local stratification, follows a monotonic exponential decay with height off the bottom, with a nonuniform decay scale. We however show that a substantial part of the dissipation occurs over the smoother flanks of mid‐ocean ridges, and exhibits a middepth maximum due to the interplay of wave amplitude with stratification. We link the three‐dimensional map of dissipation to abyssal hills characteristics, ocean stratification, and tidal forcing, and discuss its potential implementation in time‐evolving parameterizations for global climate models. Current tidal parameterizations only account for waves generated at large‐scale satellite‐resolved bathymetry. Our results suggest that the presence of small‐scale, mostly unresolved abyssal hills could significantly enhance the spatial inhomogeneity of tidal mixing, particularly above mid‐ocean ridges in the Southern Hemisphere.
AU - Lefauve, Adrien
AU - MULLER, Caroline J
AU - Melet, Angélique
ID - 9141
IS - 7
JF - Journal of Geophysical Research: Oceans
SN - 2169-9275
TI - A three-dimensional map of tidal dissipation over abyssal hills
VL - 120
ER -
TY - JOUR
AB - The actomyosin cytoskeleton is a primary force-generating mechanism in morphogenesis, thus a robust spatial control of cytoskeletal positioning is essential. In this report, we demonstrate that actomyosin contractility and planar cell polarity (PCP) interact in post-mitotic Ciona notochord cells to self-assemble and reposition actomyosin rings, which play an essential role for cell elongation. Intriguingly, rings always form at the cells′ anterior edge before migrating towards the center as contractility increases, reflecting a novel dynamical property of the cortex. Our drug and genetic manipulations uncover a tug-of-war between contractility, which localizes cortical flows toward the equator and PCP, which tries to reposition them. We develop a simple model of the physical forces underlying this tug-of-war, which quantitatively reproduces our results. We thus propose a quantitative framework for dissecting the relative contribution of contractility and PCP to the self-assembly and repositioning of cytoskeletal structures, which should be applicable to other morphogenetic events.
AU - Sehring, Ivonne
AU - Recho, Pierre
AU - Denker, Elsa
AU - Kourakis, Matthew
AU - Mathiesen, Birthe
AU - Hannezo, Edouard B
AU - Dong, Bo
AU - Jiang, Di
ID - 928
JF - eLife
TI - Assembly and positioning of actomyosin rings by contractility and planar cell polarity
VL - 4
ER -
TY - JOUR
AB - Although collective cell motion plays an important role, for example during wound healing, embryogenesis, or cancer progression, the fundamental rules governing this motion are still not well understood, in particular at high cell density. We study here the motion of human bronchial epithelial cells within a monolayer, over long times. We observe that, as the monolayer ages, the cells slow down monotonously, while the velocity correlation length first increases as the cells slow down but eventually decreases at the slowest motions. By comparing experiments, analytic model, and detailed particle-based simulations, we shed light on this biological amorphous solidification process, demonstrating that the observed dynamics can be explained as a consequence of the combined maturation and strengthening of cell-cell and cell-substrate adhesions. Surprisingly, the increase of cell surface density due to proliferation is only secondary in this process. This analysis is confirmed with two other cell types. The very general relations between the mean cell velocity and velocity correlation lengths, which apply for aggregates of self-propelled particles, as well as motile cells, can possibly be used to discriminate between various parameter changes in vivo, from noninvasive microscopy data.
AU - García, Simón
AU - Hannezo, Edouard B
AU - Elgeti, Jens
AU - Joanny, Jean
AU - Silberzan, Pascal
AU - Gov, Nir
ID - 933
IS - 50
JF - PNAS
TI - Physics of active jamming during collective cellular motion in a monolayer
VL - 112
ER -
TY - JOUR
AB - The tunability of topological surface states and controllable opening of the Dirac gap are of fundamental and practical interest in the field of topological materials. In the newly discovered topological crystalline insulators (TCIs), theory predicts that the Dirac node is protected by a crystalline symmetry and that the surface state electrons can acquire a mass if this symmetry is broken. Recent studies have detected signatures of a spontaneously generated Dirac gap in TCIs; however, the mechanism of mass formation remains elusive. In this work, we present scanning tunnelling microscopy (STM) measurements of the TCI Pb 1â'x Sn x Se for a wide range of alloy compositions spanning the topological and non-topological regimes. The STM topographies reveal a symmetry-breaking distortion on the surface, which imparts mass to the otherwise massless Dirac electrons-a mechanism analogous to the long sought-after Higgs mechanism in particle physics. Interestingly, the measured Dirac gap decreases on approaching the trivial phase, whereas the magnitude of the distortion remains nearly constant. Our data and calculations reveal that the penetration depth of Dirac surface states controls the magnitude of the Dirac mass. At the limit of the critical composition, the penetration depth is predicted to go to infinity, resulting in zero mass, consistent with our measurements. Finally, we discover the existence of surface states in the non-topological regime, which have the characteristics of gapped, double-branched Dirac fermions and could be exploited in realizing superconductivity in these materials.
AU - Zeljkovic, Ilija
AU - Okada, Yoshinori
AU - Maksym Serbyn
AU - Sankar, Raman
AU - Walkup, Daniel
AU - Zhou, Wenwen
AU - Liu, Junwei
AU - Chang, Guoqing
AU - Wang, Yungjui
AU - Hasan, Md Z
AU - Chou, Fangcheng
AU - Lin, Hsin
AU - Bansil, Arun
AU - Fu, Liang
AU - Madhavan, Vidya
ID - 981
IS - 3
JF - Nature Materials
TI - Dirac mass generation from crystal symmetry breaking on the surfaces of topological crystalline insulators
VL - 14
ER -
TY - JOUR
AB - We propose a new approach to probing ergodicity and its breakdown in one-dimensional quantum manybody systems based on their response to a local perturbation. We study the distribution of matrix elements of a local operator between the system's eigenstates, finding a qualitatively different behavior in the manybody localized (MBL) and ergodic phases. To characterize how strongly a local perturbation modifies the eigenstates, we introduce the parameter g(L) = (In (Vnm/δ)) which represents the disorder-averaged ratio of a typical matrix element of a local operator V to energy level spacing δ this parameter is reminiscent of the Thouless conductance in the single-particle localization. We show that the parameter g(L) decreases with system size L in the MBL phase and grows in the ergodic phase. We surmise that the delocalization transition occurs when g(L) is independent of system size, g(L)=gc ~ 1. We illustrate our approach by studying the many-body localization transition and resolving the many-body mobility edge in a disordered one-dimensional XXZ spin-1=2 chain using exact diagonalization and time-evolving block-decimation methods. Our criterion for the MBL transition gives insights into microscopic details of transition. Its direct physical consequences, in particular, logarithmically slow transport at the transition and extensive entanglement entropy of the eigenstates, are consistent with recent renormalization-group predictions.
AU - Maksym Serbyn
AU - Papić, Zlatko
AU - Abanin, Dmitry A
ID - 982
IS - 4
JF - Physical Review X
TI - Criterion for many-body localization-delocalization phase transition
VL - 5
ER -
TY - JOUR
AB - Quasiparticle excitations can compromise the performance of superconducting devices, causing high-frequency dissipation, decoherence in Josephson qubits, and braiding errors in proposed Majorana-based topological quantum computers. Quasiparticle dynamics have been studied in detail in metallic superconductors but remain relatively unexplored in semiconductor-superconductor structures, which are now being intensely pursued in the context of topological superconductivity. To this end, we use a system comprising a gate-confined semiconductor nanowire with an epitaxially grown superconductor layer, yielding an isolated, proximitized nanowire segment. We identify bound states in the semiconductor by means of bias spectroscopy, determine the characteristic temperatures and magnetic fields for quasiparticle excitations, and extract a parity lifetime (poisoning time) of the bound state in the semiconductor exceeding 10 ms.
AU - Higginbotham, Andrew P
AU - Albrecht, S M
AU - Kiršanskas, Gediminas
AU - Chang, W
AU - Kuemmeth, Ferdinand
AU - Krogstrup, Peter
AU - Jespersen, Thomas
AU - Nygård, Jesper
AU - Flensberg, Karsten
AU - Marcus, Charles
ID - 99
IS - 12
JF - Nature Physics
TI - Parity lifetime of bound states in a proximitized semiconductor nanowire
VL - 11
ER -
TY - JOUR
AB - We use ultrafast optical spectroscopy to observe binding of charged single-particle excitations (SE) in the magnetically frustrated Mott insulator Na2IrO3. Above the antiferromagnetic ordering temperature (TN) the system response is due to both Hubbard excitons (HE) and their constituent unpaired SE. The SE response becomes strongly suppressed immediately below TN. We argue that this increase in binding energy is due to a unique interplay between the frustrated Kitaev and the weak Heisenberg-type ordering term in the Hamiltonian, mediating an effective interaction between the spin-singlet SE. This interaction grows with distance causing the SE to become trapped in the HE, similar to quark confinement inside hadrons. This binding of charged particles, induced by magnetic ordering, is a result of a confinement-deconfinement transition of spin excitations. This observation provides evidence for spin liquid type behavior which is expected in Na2IrO3.
AU - Alpichshev, Zhanybek
AU - Mahmood, Fahad
AU - Cao, Gang
AU - Gedik, Nuh
ID - 388
IS - 1
JF - Physical Review Letters
TI - Confinement deconfinement transition as an indication of spin liquid type behavior in Na2IrO3
VL - 114
ER -
TY - THES
AB - The human ability to recognize objects in complex scenes has driven research in the computer vision field over couple of decades. This thesis focuses on the object recognition task in images. That is, given the image, we want the computer system to be able to predict the class of the object that appears in the image. A recent succesful attempt to bridge semantic understanding of the image perceived by humans and by computers uses attribute-based models. Attributes are semantic properties of the objects shared across different categories, which humans and computers can decide on. To explore the attribute-based models we take a statistical machine learning approach, and address two key learning challenges in view of object recognition task: learning augmented attributes as mid-level discriminative feature representation, and learning with attributes as privileged information. Our main contributions are parametric and non-parametric models and algorithms to solve these frameworks. In the parametric approach, we explore an autoencoder model combined with the large margin nearest neighbor principle for mid-level feature learning, and linear support vector machines for learning with privileged information. In the non-parametric approach, we propose a supervised Indian Buffet Process for automatic augmentation of semantic attributes, and explore the Gaussian Processes classification framework for learning with privileged information. A thorough experimental analysis shows the effectiveness of the proposed models in both parametric and non-parametric views.
AU - Sharmanska, Viktoriia
ID - 1401
TI - Learning with attributes for object recognition: Parametric and non-parametrics views
ER -
TY - JOUR
AB - Evolution of gene regulation is crucial for our understanding of the phenotypic differences between species, populations and individuals. Sequence-specific binding of transcription factors to the regulatory regions on the DNA is a key regulatory mechanism that determines gene expression and hence heritable phenotypic variation. We use a biophysical model for directional selection on gene expression to estimate the rates of gain and loss of transcription factor binding sites (TFBS) in finite populations under both point and insertion/deletion mutations. Our results show that these rates are typically slow for a single TFBS in an isolated DNA region, unless the selection is extremely strong. These rates decrease drastically with increasing TFBS length or increasingly specific protein-DNA interactions, making the evolution of sites longer than ∼ 10 bp unlikely on typical eukaryotic speciation timescales. Similarly, evolution converges to the stationary distribution of binding sequences very slowly, making the equilibrium assumption questionable. The availability of longer regulatory sequences in which multiple binding sites can evolve simultaneously, the presence of “pre-sites” or partially decayed old sites in the initial sequence, and biophysical cooperativity between transcription factors, can all facilitate gain of TFBS and reconcile theoretical calculations with timescales inferred from comparative genomics.
AU - Tugrul, Murat
AU - Paixao, Tiago
AU - Barton, Nicholas H
AU - Tkacik, Gasper
ID - 1666
IS - 11
JF - PLoS Genetics
TI - Dynamics of transcription factor binding site evolution
VL - 11
ER -
TY - GEN
AB - We study conditions under which a finite simplicial complex $K$ can be mapped to $\mathbb R^d$ without higher-multiplicity intersections. An almost $r$-embedding is a map $f: K\to \mathbb R^d$ such that the images of any $r$
pairwise disjoint simplices of $K$ do not have a common point. We show that if $r$ is not a prime power and $d\geq 2r+1$, then there is a counterexample to the topological Tverberg conjecture, i.e., there is an almost $r$-embedding of
the $(d+1)(r-1)$-simplex in $\mathbb R^d$. This improves on previous constructions of counterexamples (for $d\geq 3r$) based on a series of papers by M. \"Ozaydin, M. Gromov, P. Blagojevi\'c, F. Frick, G. Ziegler, and the second and fourth present authors. The counterexamples are obtained by proving the following algebraic criterion in codimension 2: If $r\ge3$ and if $K$ is a finite $2(r-1)$-complex then there exists an almost $r$-embedding $K\to \mathbb R^{2r}$ if and only if there exists a general position PL map $f:K\to \mathbb R^{2r}$ such that the algebraic intersection number of the $f$-images of any $r$ pairwise disjoint simplices of $K$ is zero. This result can be restated in terms of cohomological obstructions or equivariant maps, and extends an analogous codimension 3 criterion by the second and fourth authors. As another application we classify ornaments $f:S^3 \sqcup S^3\sqcup S^3\to \mathbb R^5$ up to ornament
concordance. It follows from work of M. Freedman, V. Krushkal and P. Teichner that the analogous criterion for $r=2$ is false. We prove a lemma on singular higher-dimensional Borromean rings, yielding an elementary proof of the counterexample.
AU - Avvakumov, Sergey
AU - Mabillard, Isaac
AU - Skopenkov, A.
AU - Wagner, Uli
ID - 8183
T2 - arXiv
TI - Eliminating higher-multiplicity intersections, III. Codimension 2
ER -
TY - JOUR
AB - Parasitism creates selection for resistance mechanisms in host populations and is hypothesized to promote increased host evolvability. However, the influence of these traits on host evolution when parasites are no longer present is unclear. We used experimental evolution and whole-genome sequencing of Escherichia coli to determine the effects of past and present exposure to parasitic viruses (phages) on the spread of mutator alleles, resistance, and bacterial competitive fitness. We found that mutator alleles spread rapidly during adaptation to any of four different phage species, and this pattern was even more pronounced with multiple phages present simultaneously. However, hypermutability did not detectably accelerate adaptation in the absence of phages and recovery of fitness costs associated with resistance. Several lineages evolved phage resistance through elevated mucoidy, and during subsequent evolution in phage-free conditions they rapidly reverted to nonmucoid, phage-susceptible phenotypes. Genome sequencing revealed that this phenotypic reversion was achieved by additional genetic changes rather than by genotypic reversion of the initial resistance mutations. Insertion sequence (IS) elements played a key role in both the acquisition of resistance and adaptation in the absence of parasites; unlike single nucleotide polymorphisms, IS insertions were not more frequent in mutator lineages. Our results provide a genetic explanation for rapid reversion of mucoidy, a phenotype observed in other bacterial species including human pathogens. Moreover, this demonstrates that the types of genetic change underlying adaptation to fitness costs, and consequently the impact of evolvability mechanisms such as increased point-mutation rates, depend critically on the mechanism of resistance.
AU - Wielgoss, Sébastien
AU - Bergmiller, Tobias
AU - Bischofberger, Anna M.
AU - Hall, Alex R.
ID - 5749
IS - 3
JF - Molecular Biology and Evolution
SN - 0737-4038
TI - Adaptation to Parasites and Costs of Parasite Resistance in Mutator and Nonmutator Bacteria
VL - 33
ER -
TY - CONF
AB - We consider the core algorithmic problems related to verification of systems with respect to three classical quantitative properties, namely, the mean-payoff property, the ratio property, and the minimum initial credit for energy property. The algorithmic problem given a graph and a quantitative property asks to compute the optimal value (the infimum value over all traces) from every node of the graph. We consider graphs with constant treewidth, and it is well-known that the control-flow graphs of most programs have constant treewidth. Let n denote the number of nodes of a graph, m the number of edges (for constant treewidth graphs m=O(n)) and W the largest absolute value of the weights. Our main theoretical results are as follows. First, for constant treewidth graphs we present an algorithm that approximates the mean-payoff value within a multiplicative factor of ϵ in time O(n⋅log(n/ϵ)) and linear space, as compared to the classical algorithms that require quadratic time. Second, for the ratio property we present an algorithm that for constant treewidth graphs works in time O(n⋅log(|a⋅b|))=O(n⋅log(n⋅W)), when the output is ab, as compared to the previously best known algorithm with running time O(n2⋅log(n⋅W)). Third, for the minimum initial credit problem we show that (i) for general graphs the problem can be solved in O(n2⋅m) time and the associated decision problem can be solved in O(n⋅m) time, improving the previous known O(n3⋅m⋅log(n⋅W)) and O(n2⋅m) bounds, respectively; and (ii) for constant treewidth graphs we present an algorithm that requires O(n⋅logn) time, improving the previous known O(n4⋅log(n⋅W)) bound. We have implemented some of our algorithms and show that they present a significant speedup on standard benchmarks.
AU - Chatterjee, Krishnendu
AU - Ibsen-Jensen, Rasmus
AU - Pavlogiannis, Andreas
ID - 1607
TI - Faster algorithms for quantitative verification in constant treewidth graphs
VL - 9206
ER -
TY - JOUR
AB - Genomic imprinting, an inherently epigenetic phenomenon defined by parent of origin-dependent gene expression, is observed in mammals and flowering plants. Genome-scale surveys of imprinted expression and the underlying differential epigenetic marks have led to the discovery of hundreds of imprinted plant genes and confirmed DNA and histone methylation as key regulators of plant imprinting. However, the biological roles of the vast majority of imprinted plant genes are unknown, and the evolutionary forces shaping plant imprinting remain rather opaque. Here, we review the mechanisms of plant genomic imprinting and discuss theories of imprinting evolution and biological significance in light of recent findings.
AU - Rodrigues, Jessica A.
AU - ZILBERMAN, Daniel
ID - 9532
IS - 24
JF - Genes and Development
SN - 0890-9369
TI - Evolution and function of genomic imprinting in plants
VL - 29
ER -
TY - JOUR
AB - We give several results showing that different discrete structures typically gain certain spanning substructures (in particular, Hamilton cycles) after a modest random perturbation. First, we prove that adding linearly many random edges to a dense k-uniform hypergraph ensures the (asymptotically almost sure) existence of a perfect matching or a loose Hamilton cycle. The proof involves an interesting application of Szemerédi's Regularity Lemma, which might be independently useful. We next prove that digraphs with certain strong expansion properties are pancyclic, and use this to show that adding a linear number of random edges typically makes a dense digraph pancyclic. Finally, we prove that perturbing a certain (minimum-degree-dependent) number of random edges in a tournament typically ensures the existence of multiple edge-disjoint Hamilton cycles. All our results are tight.
AU - Krivelevich, Michael
AU - Kwan, Matthew Alan
AU - Sudakov, Benny
ID - 9575
JF - Electronic Notes in Discrete Mathematics
SN - 1571-0653
TI - Cycles and matchings in randomly perturbed digraphs and hypergraphs
VL - 49
ER -
TY - JOUR
AB - The emergence of drug resistant pathogens is a serious public health problem. It is a long-standing goal to predict rates of resistance evolution and design optimal treatment strategies accordingly. To this end, it is crucial to reveal the underlying causes of drug-specific differences in the evolutionary dynamics leading to resistance. However, it remains largely unknown why the rates of resistance evolution via spontaneous mutations and the diversity of mutational paths vary substantially between drugs. Here we comprehensively quantify the distribution of fitness effects (DFE) of mutations, a key determinant of evolutionary dynamics, in the presence of eight antibiotics representing the main modes of action. Using precise high-throughput fitness measurements for genome-wide Escherichia coli gene deletion strains, we find that the width of the DFE varies dramatically between antibiotics and, contrary to conventional wisdom, for some drugs the DFE width is lower than in the absence of stress. We show that this previously underappreciated divergence in DFE width among antibiotics is largely caused by their distinct drug-specific dose-response characteristics. Unlike the DFE, the magnitude of the changes in tolerated drug concentration resulting from genome-wide mutations is similar for most drugs but exceptionally small for the antibiotic nitrofurantoin, i.e., mutations generally have considerably smaller resistance effects for nitrofurantoin than for other drugs. A population genetics model predicts that resistance evolution for drugs with this property is severely limited and confined to reproducible mutational paths. We tested this prediction in laboratory evolution experiments using the “morbidostat”, a device for evolving bacteria in well-controlled drug environments. Nitrofurantoin resistance indeed evolved extremely slowly via reproducible mutations—an almost paradoxical behavior since this drug causes DNA damage and increases the mutation rate. Overall, we identified novel quantitative characteristics of the evolutionary landscape that provide the conceptual foundation for predicting the dynamics of drug resistance evolution.
AU - Chevereau, Guillaume
AU - Dravecka, Marta
AU - Batur, Tugce
AU - Guvenek, Aysegul
AU - Ayhan, Dilay
AU - Toprak, Erdal
AU - Bollenbach, Mark Tobias
ID - 1619
IS - 11
JF - PLoS Biology
TI - Quantifying the determinants of evolutionary dynamics leading to drug resistance
VL - 13
ER -
TY - JOUR
AB - To reveal the full potential of human pluripotent stem cells, new methods for rapid, site-specific genomic engineering are needed. Here, we describe a system for precise genetic modification of human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). We identified a novel human locus, H11, located in a safe, intergenic, transcriptionally active region of chromosome 22, as the recipient site, to provide robust, ubiquitous expression of inserted genes. Recipient cell lines were established by site-specific placement of a ‘landing pad’ cassette carrying attP sites for phiC31 and Bxb1 integrases at the H11 locus by spontaneous or TALEN-assisted homologous recombination. Dual integrase cassette exchange (DICE) mediated by phiC31 and Bxb1 integrases was used to insert genes of interest flanked by phiC31 and Bxb1 attB sites at the H11 locus, replacing the landing pad. This system provided complete control over content, direction and copy number of inserted genes, with a specificity of 100%. A series of genes, including mCherry and various combinations of the neural transcription factors LMX1a, FOXA2 and OTX2, were inserted in recipient cell lines derived from H9 ESC, as well as iPSC lines derived from a Parkinson’s disease patient and a normal sibling control. The DICE system offers rapid, efficient and precise gene insertion in ESC and iPSC and is particularly well suited for repeated modifications of the same locus.
AU - Zhu, Fangfang
AU - Gamboa, Matthew
AU - Farruggio, Alfonso
AU - Hippenmeyer, Simon
AU - Tasic, Bosiljka
AU - Schüle, Birgitt
AU - Chen Tsai, Yanru
AU - Calos, Michele
ID - 2261
IS - 5
JF - Nucleic Acids Research
TI - DICE, an efficient system for iterative genomic editing in human pluripotent stem cells
VL - 42
ER -
TY - CONF
AB - Energies with high-order non-submodular interactions have been shown to be very useful in vision due to their high modeling power. Optimization of such energies, however, is generally NP-hard. A naive approach that works for small problem instances is exhaustive search, that is, enumeration of all possible labelings of the underlying graph. We propose a general minimization approach for large graphs based on enumeration of labelings of certain small patches.
This partial enumeration technique reduces complex high-order energy formulations to pairwise Constraint Satisfaction Problems with unary costs (uCSP), which can be efficiently solved using standard methods like TRW-S. Our approach outperforms a number of existing state-of-the-art algorithms on well known difficult problems (e.g. curvature regularization, stereo, deconvolution); it gives near global minimum and better speed.
Our main application of interest is curvature regularization. In the context of segmentation, our partial enumeration technique allows to evaluate curvature directly on small patches using a novel integral geometry approach.
AU - Olsson, Carl
AU - Ulen, Johannes
AU - Boykov, Yuri
AU - Kolmogorov, Vladimir
ID - 2275
TI - Partial enumeration and curvature regularization
ER -