TY - JOUR
AB - We consider Ising models in d = 2 and d = 3 dimensions with nearest neighbor ferromagnetic and long-range antiferromagnetic interactions, the latter decaying as (distance)-p, p > 2d, at large distances. If the strength J of the ferromagnetic interaction is larger than a critical value J c, then the ground state is homogeneous. It has been conjectured that when J is smaller than but close to J c, the ground state is periodic and striped, with stripes of constant width h = h(J), and h → ∞ as J → Jc -. (In d = 3 stripes mean slabs, not columns.) Here we rigorously prove that, if we normalize the energy in such a way that the energy of the homogeneous state is zero, then the ratio e 0(J)/e S(J) tends to 1 as J → Jc -, with e S(J) being the energy per site of the optimal periodic striped/slabbed state and e 0(J) the actual ground state energy per site of the system. Our proof comes with explicit bounds on the difference e 0(J)-e S(J) at small but positive J c-J, and also shows that in this parameter range the ground state is striped/slabbed in a certain sense: namely, if one looks at a randomly chosen window, of suitable size ℓ (very large compared to the optimal stripe size h(J)), one finds a striped/slabbed state with high probability.
AU - Giuliani, Alessandro
AU - Lieb, Élliott
AU - Seiringer, Robert
ID - 1935
JF - Communications in Mathematical Physics
SN - 0010-3616
TI - Formation of stripes and slabs near the ferromagnetic transition
VL - 331
ER -
TY - JOUR
AB - The social intelligence hypothesis states that the need to cope with complexities of social life has driven the evolution of advanced cognitive abilities. It is usually invoked in the context of challenges arising from complex intragroup structures, hierarchies, and alliances. However, a fundamental aspect of group living remains largely unexplored as a driving force in cognitive evolution: the competition between individuals searching for resources (producers) and conspecifics that parasitize their findings (scroungers). In populations of social foragers, abilities that enable scroungers to steal by outsmarting producers, and those allowing producers to prevent theft by outsmarting scroungers, are likely to be beneficial and may fuel a cognitive arms race. Using analytical theory and agent-based simulations, we present a general model for such a race that is driven by the producer-scrounger game and show that the race's plausibility is dramatically affected by the nature of the evolving abilities. If scrounging and scrounging avoidance rely on separate, strategy-specific cognitive abilities, arms races are short-lived and have a limited effect on cognition. However, general cognitive abilities that facilitate both scrounging and scrounging avoidance undergo stable, long-lasting arms races. Thus, ubiquitous foraging interactions may lead to the evolution of general cognitive abilities in social animals, without the requirement of complex intragroup structures.
AU - Arbilly, Michal
AU - Weissman, Daniel
AU - Feldman, Marcus
AU - Grodzinski, Uri
ID - 1936
IS - 3
JF - Behavioral Ecology
TI - An arms race between producers and scroungers can drive the evolution of social cognition
VL - 25
ER -
TY - JOUR
AB - The plant hormones auxin and cytokinin mutually coordinate their activities to control various aspects of development [1-9], and their crosstalk occurs at multiple levels [10, 11]. Cytokinin-mediated modulation of auxin transport provides an efficient means to regulate auxin distribution in plant organs. Here, we demonstrate that cytokinin does not merely control the overall auxin flow capacity, but might also act as a polarizing cue and control the auxin stream directionality during plant organogenesis. Cytokinin enhances the PIN-FORMED1 (PIN1) auxin transporter depletion at specific polar domains, thus rearranging the cellular PIN polarities and directly regulating the auxin flow direction. This selective cytokinin sensitivity correlates with the PIN protein phosphorylation degree. PIN1 phosphomimicking mutations, as well as enhanced phosphorylation in plants with modulated activities of PIN-specific kinases and phosphatases, desensitize PIN1 to cytokinin. Our results reveal conceptually novel, cytokinin-driven polarization mechanism that operates in developmental processes involving rapid auxin stream redirection, such as lateral root organogenesis, in which a gradual PIN polarity switch defines the growth axis of the newly formed organ.
AU - Marhavy, Peter
AU - Duclercq, Jérôme
AU - Weller, Benjamin
AU - Feraru, Elena
AU - Bielach, Agnieszka
AU - Offringa, Remko
AU - Friml, Jirí
AU - Schwechheimer, Claus
AU - Murphy, Angus
AU - Benková, Eva
ID - 1934
IS - 9
JF - Current Biology
TI - Cytokinin controls polarity of PIN1-dependent Auxin transport during lateral root organogenesis
VL - 24
ER -
TY - JOUR
AB - The existence of complex (multiple-step) genetic adaptations that are "irreducible" (i.e., all partial combinations are less fit than the original genotype) is one of the longest standing problems in evolutionary biology. In standard genetics parlance, these adaptations require the crossing of a wide adaptive valley of deleterious intermediate stages. Here, we demonstrate, using a simple model, that evolution can cross wide valleys to produce "irreducibly complex" adaptations by making use of previously cryptic mutations. When revealed by an evolutionary capacitor, previously cryptic mutants have higher initial frequencies than do new mutations, bringing them closer to a valley-crossing saddle in allele frequency space. Moreover, simple combinatorics implies an enormous number of candidate combinations exist within available cryptic genetic variation. We model the dynamics of crossing of a wide adaptive valley after a capacitance event using both numerical simulations and analytical approximations. Although individual valley crossing events become less likely as valleys widen, by taking the combinatorics of genotype space into account, we see that revealing cryptic variation can cause the frequent evolution of complex adaptations.
AU - Trotter, Meredith
AU - Weissman, Daniel
AU - Peterson, Grant
AU - Peck, Kayla
AU - Masel, Joanna
ID - 1932
IS - 12
JF - Evolution
TI - Cryptic genetic variation can make "irreducible complexity" a common mode of adaptation in sexual populations
VL - 68
ER -
TY - JOUR
AB - (Figure Presented) Data acquisition, numerical inaccuracies, and sampling often introduce noise in measurements and simulations. Removing this noise is often necessary for efficient analysis and visualization of this data, yet many denoising techniques change the minima and maxima of a scalar field. For example, the extrema can appear or disappear, spatially move, and change their value. This can lead to wrong interpretations of the data, e.g., when the maximum temperature over an area is falsely reported being a few degrees cooler because the denoising method is unaware of these features. Recently, a topological denoising technique based on a global energy optimization was proposed, which allows the topology-controlled denoising of 2D scalar fields. While this method preserves the minima and maxima, it is constrained by the size of the data. We extend this work to large 2D data and medium-sized 3D data by introducing a novel domain decomposition approach. It allows processing small patches of the domain independently while still avoiding the introduction of new critical points. Furthermore, we propose an iterative refinement of the solution, which decreases the optimization energy compared to the previous approach and therefore gives smoother results that are closer to the input. We illustrate our technique on synthetic and real-world 2D and 3D data sets that highlight potential applications.
AU - Günther, David
AU - Jacobson, Alec
AU - Reininghaus, Jan
AU - Seidel, Hans
AU - Sorkine Hornung, Olga
AU - Weinkauf, Tino
ID - 1930
IS - 12
JF - IEEE Transactions on Visualization and Computer Graphics
TI - Fast and memory-efficient topological denoising of 2D and 3D scalar fields
VL - 20
ER -
TY - JOUR
AB - The development of the vertebrate brain requires an exquisite balance between proliferation and differentiation of neural progenitors. Notch signaling plays a pivotal role in regulating this balance, yet the interaction between signaling and receiving cells remains poorly understood. We have found that numerous nascent neurons and/or intermediate neurogenic progenitors expressing the ligand of Notch retain apical endfeet transiently at the ventricular lumen that form adherens junctions (AJs) with the endfeet of progenitors. Forced detachment of the apical endfeet of those differentiating cells by disrupting AJs resulted in precocious neurogenesis that was preceded by the downregulation of Notch signaling. Both Notch1 and its ligand Dll1 are distributed around AJs in the apical endfeet, and these proteins physically interact with ZO-1, a constituent of the AJ. Furthermore, live imaging of a fluorescently tagged Notch1 demonstrated its trafficking from the apical endfoot to the nucleus upon cleavage. Our results identified the apical endfoot as the central site of active Notch signaling to securely prohibit inappropriate differentiation of neural progenitors.
AU - Hatakeyama, Jun
AU - Wakamatsu, Yoshio
AU - Nagafuchi, Akira
AU - Kageyama, Ryoichiro
AU - Shigemoto, Ryuichi
AU - Shimamura, Kenji
ID - 1933
IS - 8
JF - Development
TI - Cadherin-based adhesions in the apical endfoot are required for active Notch signaling to control neurogenesis in vertebrates
VL - 141
ER -
TY - JOUR
AB - A wealth of experimental evidence suggests that working memory circuits preferentially represent information that is behaviorally relevant. Still, we are missing a mechanistic account of how these representations come about. Here we provide a simple explanation for a range of experimental findings, in light of prefrontal circuits adapting to task constraints by reward-dependent learning. In particular, we model a neural network shaped by reward-modulated spike-timing dependent plasticity (r-STDP) and homeostatic plasticity (intrinsic excitability and synaptic scaling). We show that the experimentally-observed neural representations naturally emerge in an initially unstructured circuit as it learns to solve several working memory tasks. These results point to a critical, and previously unappreciated, role for reward-dependent learning in shaping prefrontal cortex activity.
AU - Savin, Cristina
AU - Triesch, Jochen
ID - 1931
IS - MAY
JF - Frontiers in Computational Neuroscience
TI - Emergence of task-dependent representations in working memory circuits
VL - 8
ER -
TY - JOUR
AB - We prove the edge universality of the beta ensembles for any β ≥ 1, provided that the limiting spectrum is supported on a single interval, and the external potential is C4 and regular. We also prove that the edge universality holds for generalized Wigner matrices for all symmetry classes. Moreover, our results allow us to extend bulk universality for beta ensembles from analytic potentials to potentials in class C4.
AU - Bourgade, Paul
AU - Erdös, László
AU - Yau, Horngtzer
ID - 1937
IS - 1
JF - Communications in Mathematical Physics
TI - Edge universality of beta ensembles
VL - 332
ER -
TY - JOUR
AB - Auxin polar transport, local maxima, and gradients have become an importantmodel system for studying self-organization. Auxin distribution is regulated by auxin-dependent positive feedback loops that are not well-understood at the molecular level. Previously, we showed the involvement of the RHO of Plants (ROP) effector INTERACTOR of CONSTITUTIVELY active ROP 1 (ICR1) in regulation of auxin transport and that ICR1 levels are posttranscriptionally repressed at the site of maximum auxin accumulation at the root tip. Here, we show that bimodal regulation of ICR1 levels by auxin is essential for regulating formation of auxin local maxima and gradients. ICR1 levels increase concomitant with increase in auxin response in lateral root primordia, cotyledon tips, and provascular tissues. However, in the embryo hypophysis and root meristem, when auxin exceeds critical levels, ICR1 is rapidly destabilized by an SCF(TIR1/AFB) [SKP, Cullin, F-box (transport inhibitor response 1/auxin signaling F-box protein)]-dependent auxin signaling mechanism. Furthermore, ectopic expression of ICR1 in the embryo hypophysis resulted in reduction of auxin accumulation and concomitant root growth arrest. ICR1 disappeared during root regeneration and lateral root initiation concomitantly with the formation of a local auxin maximum in response to external auxin treatments and transiently after gravitropic stimulation. Destabilization of ICR1 was impaired after inhibition of auxin transport and signaling, proteasome function, and protein synthesis. A mathematical model based on these findings shows that an in vivo-like auxin distribution, rootward auxin flux, and shootward reflux can be simulated without assuming preexisting tissue polarity. Our experimental results and mathematical modeling indicate that regulation of auxin distribution is tightly associated with auxin-dependent ICR1 levels.
AU - Hazak, Ora
AU - Obolski, Uri
AU - Prat, Tomas
AU - Friml, Jiří
AU - Hadany, Lilach
AU - Yalovsky, Shaul
ID - 1996
IS - 50
JF - PNAS
TI - Bimodal regulation of ICR1 levels generates self-organizing auxin distribution
VL - 111
ER -
TY - JOUR
AB - The emergence and radiation of multicellular land plants was driven by crucial innovations to their body plans [1]. The directional transport of the phytohormone auxin represents a key, plant-specific mechanism for polarization and patterning in complex seed plants [2-5]. Here, we show that already in the early diverging land plant lineage, as exemplified by the moss Physcomitrella patens, auxin transport by PIN transporters is operational and diversified into ER-localized and plasma membrane-localized PIN proteins. Gain-of-function and loss-of-function analyses revealed that PIN-dependent intercellular auxin transport in Physcomitrella mediates crucial developmental transitions in tip-growing filaments and waves of polarization and differentiation in leaf-like structures. Plasma membrane PIN proteins localize in a polar manner to the tips of moss filaments, revealing an unexpected relation between polarization mechanisms in moss tip-growing cells and multicellular tissues of seed plants. Our results trace the origins of polarization and auxin-mediated patterning mechanisms and highlight the crucial role of polarized auxin transport during the evolution of multicellular land plants.
AU - Viaene, Tom
AU - Landberg, Katarina
AU - Thelander, Mattias
AU - Medvecka, Eva
AU - Pederson, Eric
AU - Feraru, Elena
AU - Cooper, Endymion
AU - Karimi, Mansour
AU - Delwiche, Charles
AU - Ljung, Karin
AU - Geisler, Markus
AU - Sundberg, Eva
AU - Friml, Jirí
ID - 1994
IS - 23
JF - Current Biology
TI - Directional auxin transport mechanisms in early diverging land plants
VL - 24
ER -
TY - JOUR
AB - Optical transport represents a natural route towards fast communications, and it is currently used in large scale data transfer. The progressive miniaturization of devices for information processing calls for the microscopic tailoring of light transport and confinement at length scales appropriate for upcoming technologies. With this goal in mind, we present a theoretical analysis of a one-dimensional Fabry-Perot interferometer built with two highly saturable nonlinear mirrors: a pair of two-level systems. Our approach captures nonlinear and nonreciprocal effects of light transport that were not reported previously. Remarkably, we show that such an elementary device can operate as a microscopic integrated optical rectifier.
AU - Fratini, Filippo
AU - Mascarenhas, Eduardo
AU - Safari, Laleh
AU - Poizat, Jean
AU - Valente, Daniel
AU - Auffèves, Alexia
AU - Gerace, Dario
AU - Santos, Marcelo
ID - 1995
IS - 24
JF - Physical Review Letters
TI - Fabry-Perot interferometer with quantum mirrors: Nonlinear light transport and rectification
VL - 113
ER -
TY - JOUR
AB - Immune systems are able to protect the body against secondary infection with the same parasite. In insect colonies, this protection is not restricted to the level of the individual organism, but also occurs at the societal level. Here, we review recent evidence for and insights into the mechanisms underlying individual and social immunisation in insects. We disentangle general immune-protective effects from specific immune memory (priming), and examine immunisation in the context of the lifetime of an individual and that of a colony, and of transgenerational immunisation that benefits offspring. When appropriate, we discuss parallels with disease defence strategies in human societies. We propose that recurrent parasitic threats have shaped the evolution of both the individual immune systems and colony-level social immunity in insects.
AU - El Masri, Leila
AU - Cremer, Sylvia
ID - 1998
IS - 10
JF - Trends in Immunology
TI - Individual and social immunisation in insects
VL - 35
ER -
TY - JOUR
AB - Oriens-lacunosum moleculare (O-LM) interneurons in the CA1 region of the hippocampus play a key role in feedback inhibition and in the control of network activity. However, how these cells are efficiently activated in the network remains unclear. To address this question, I performed recordings from CA1 pyramidal neuron axons, the presynaptic fibers that provide feedback innervation of these interneurons. Two forms of axonal action potential (AP) modulation were identified. First, repetitive stimulation resulted in activity-dependent AP broadening. Broadening showed fast onset, with marked changes in AP shape following a single AP. Second, tonic depolarization in CA1 pyramidal neuron somata induced AP broadening in the axon, and depolarization-induced broadening summated with activity-dependent broadening. Outsideout patch recordings from CA1 pyramidal neuron axons revealed a high density of a-dendrotoxin (α-DTX)-sensitive, inactivating K+ channels, suggesting that K+ channel inactivation mechanistically contributes to AP broadening. To examine the functional consequences of axonal AP modulation for synaptic transmission, I performed paired recordings between synaptically connected CA1 pyramidal neurons and O-LM interneurons. CA1 pyramidal neuron-O-LM interneuron excitatory postsynaptic currents (EPSCs) showed facilitation during both repetitive stimulation and tonic depolarization of the presynaptic neuron. Both effects were mimicked and occluded by α-DTX, suggesting that they were mediated by K+ channel inactivation. Therefore, axonal AP modulation can greatly facilitate the activation of O-LM interneurons. In conclusion, modulation of AP shape in CA1 pyramidal neuron axons substantially enhances the efficacy of principal neuron-interneuron synapses, promoting the activation of O-LM interneurons in recurrent inhibitory microcircuits.
AU - Kim, Sooyun
ID - 2002
IS - 11
JF - PLoS One
TI - Action potential modulation in CA1 pyramidal neuron axons facilitates OLM interneuron activation in recurrent inhibitory microcircuits of rat hippocampus
VL - 9
ER -
TY - JOUR
AB - Learning can be facilitated by previous knowledge when it is organized into relational representations forming schemas. In this issue of Neuron, McKenzie et al. (2014) demonstrate that the hippocampus rapidly forms interrelated, hierarchical memory representations to support schema-based learning.
AU - O'Neill, Joseph
AU - Csicsvari, Jozsef L
ID - 2003
IS - 1
JF - Neuron
TI - Learning by example in the hippocampus
VL - 83
ER -
TY - JOUR
AB - The protection of privacy of individual-level information in genome-wide association study (GWAS) databases has been a major concern of researchers following the publication of “an attack” on GWAS data by Homer et al. (2008). Traditional statistical methods for confidentiality and privacy protection of statistical databases do not scale well to deal with GWAS data, especially in terms of guarantees regarding protection from linkage to external information. The more recent concept of differential privacy, introduced by the cryptographic community, is an approach that provides a rigorous definition of privacy with meaningful privacy guarantees in the presence of arbitrary external information, although the guarantees may come at a serious price in terms of data utility. Building on such notions, Uhler et al. (2013) proposed new methods to release aggregate GWAS data without compromising an individual’s privacy. We extend the methods developed in Uhler et al. (2013) for releasing differentially-private χ2χ2-statistics by allowing for arbitrary number of cases and controls, and for releasing differentially-private allelic test statistics. We also provide a new interpretation by assuming the controls’ data are known, which is a realistic assumption because some GWAS use publicly available data as controls. We assess the performance of the proposed methods through a risk-utility analysis on a real data set consisting of DNA samples collected by the Wellcome Trust Case Control Consortium and compare the methods with the differentially-private release mechanism proposed by Johnson and Shmatikov (2013).
AU - Yu, Fei
AU - Fienberg, Stephen
AU - Slaković, Alexandra
AU - Uhler, Caroline
ID - 2011
JF - Journal of Biomedical Informatics
TI - Scalable privacy-preserving data sharing methodology for genome-wide association studies
VL - 50
ER -
TY - CONF
AB - The classical sphere packing problem asks for the best (infinite) arrangement of non-overlapping unit balls which cover as much space as possible. We define a generalized version of the problem, where we allow each ball a limited amount of overlap with other balls. We study two natural choices of overlap measures and obtain the optimal lattice packings in a parameterized family of lattices which contains the FCC, BCC, and integer lattice.
AU - Iglesias Ham, Mabel
AU - Kerber, Michael
AU - Uhler, Caroline
ID - 2012
TI - Sphere packing with limited overlap
ER -
TY - JOUR
AB - By eliciting a natural exploratory behavior in rats, head scanning, a study reveals that hippocampal place cells form new, stable firing fields in those locations where the behavior has just occurred.
AU - Dupret, David
AU - Csicsvari, Jozsef L
ID - 2005
IS - 5
JF - Nature Neuroscience
TI - Turning heads to remember places
VL - 17
ER -
TY - GEN
AB - Maximum likelihood estimation under relational models, with or without the overall effect. For more information see the reference manual
AU - Klimova, Anna
AU - Rudas, Tamás
ID - 2007
TI - gIPFrm: Generalized iterative proportional fitting for relational models
ER -
TY - JOUR
AB - Synaptic cell adhesion molecules are increasingly gaining attention for conferring specific properties to individual synapses. Netrin-G1 and netrin-G2 are trans-synaptic adhesion molecules that distribute on distinct axons, and their presence restricts the expression of their cognate receptors, NGL1 and NGL2, respectively, to specific subdendritic segments of target neurons. However, the neural circuits and functional roles of netrin-G isoform complexes remain unclear. Here, we use netrin-G-KO and NGL-KO mice to reveal that netrin-G1/NGL1 and netrin-G2/NGL2 interactions specify excitatory synapses in independent hippocampal pathways. In the hippocampal CA1 area, netrin-G1/NGL1 and netrin-G2/NGL2 were expressed in the temporoammonic and Schaffer collateral pathways, respectively. The lack of presynaptic netrin-Gs led to the dispersion of NGLs from postsynaptic membranes. In accord, netrin-G mutant synapses displayed opposing phenotypes in long-term and short-term plasticity through discrete biochemical pathways. The plasticity phenotypes in netrin-G-KOs were phenocopied in NGL-KOs, with a corresponding loss of netrin-Gs from presynaptic membranes. Our findings show that netrin-G/NGL interactions differentially control synaptic plasticity in distinct circuits via retrograde signaling mechanisms and explain how synaptic inputs are diversified to control neuronal activity.
AU - Matsukawa, Hiroshi
AU - Akiyoshi Nishimura, Sachiko
AU - Zhang, Qi
AU - Luján, Rafael
AU - Yamaguchi, Kazuhiko
AU - Goto, Hiromichi
AU - Yaguchi, Kunio
AU - Hashikawa, Tsutomu
AU - Sano, Chie
AU - Shigemoto, Ryuichi
AU - Nakashiba, Toshiaki
AU - Itohara, Shigeyoshi
ID - 2018
IS - 47
JF - Journal of Neuroscience
SN - 0270-6474
TI - Netrin-G/NGL complexes encode functional synaptic diversification
VL - 34
ER -
TY - JOUR
AB - We prove that the empirical density of states of quantum spin glasses on arbitrary graphs converges to a normal distribution as long as the maximal degree is negligible compared with the total number of edges. This extends the recent results of Keating et al. (2014) that were proved for graphs with bounded chromatic number and with symmetric coupling distribution. Furthermore, we generalise the result to arbitrary hypergraphs. We test the optimality of our condition on the maximal degree for p-uniform hypergraphs that correspond to p-spin glass Hamiltonians acting on n distinguishable spin- 1/2 particles. At the critical threshold p = n1/2 we find a sharp classical-quantum phase transition between the normal distribution and the Wigner semicircle law. The former is characteristic to classical systems with commuting variables, while the latter is a signature of noncommutative random matrix theory.
AU - Erdös, László
AU - Schröder, Dominik J
ID - 2019
IS - 3-4
JF - Mathematical Physics, Analysis and Geometry
TI - Phase transition in the density of states of quantum spin glasses
VL - 17
ER -
TY - JOUR
AB - An asymptotic theory is developed for computing volumes of regions in the parameter space of a directed Gaussian graphical model that are obtained by bounding partial correlations. We study these volumes using the method of real log canonical thresholds from algebraic geometry. Our analysis involves the computation of the singular loci of correlation hypersurfaces. Statistical applications include the strong-faithfulness assumption for the PC algorithm and the quantification of confounder bias in causal inference. A detailed analysis is presented for trees, bow ties, tripartite graphs, and complete graphs.
AU - Lin, Shaowei
AU - Uhler, Caroline
AU - Sturmfels, Bernd
AU - Bühlmann, Peter
ID - 2013
IS - 5
JF - Foundations of Computational Mathematics
TI - Hypersurfaces and their singularities in partial correlation testing
VL - 14
ER -
TY - JOUR
AB - Radial glial progenitors (RGPs) are responsible for producing nearly all neocortical neurons. To gain insight into the patterns of RGP division and neuron production, we quantitatively analyzed excitatory neuron genesis in the mouse neocortex using Mosaic Analysis with Double Markers, which provides single-cell resolution of progenitor division patterns and potential in vivo. We found that RGPs progress through a coherent program in which their proliferative potential diminishes in a predictable manner. Upon entry into the neurogenic phase, individual RGPs produce ∼8–9 neurons distributed in both deep and superficial layers, indicating a unitary output in neuronal production. Removal of OTX1, a transcription factor transiently expressed in RGPs, results in both deep- and superficial-layer neuron loss and a reduction in neuronal unit size. Moreover, ∼1/6 of neurogenic RGPs proceed to produce glia. These results suggest that progenitor behavior and histogenesis in the mammalian neocortex conform to a remarkably orderly and deterministic program.
AU - Gao, Peng
AU - Postiglione, Maria P
AU - Krieger, Teresa
AU - Hernandez, Luisirene
AU - Wang, Chao
AU - Han, Zhi
AU - Streicher, Carmen
AU - Papusheva, Ekaterina
AU - Insolera, Ryan
AU - Chugh, Kritika
AU - Kodish, Oren
AU - Huang, Kun
AU - Simons, Benjamin
AU - Luo, Liqun
AU - Hippenmeyer, Simon
AU - Shi, Song
ID - 2022
IS - 4
JF - Cell
TI - Deterministic progenitor behavior and unitary production of neurons in the neocortex
VL - 159
ER -
TY - JOUR
AB - The mammalian heart has long been considered a postmitotic organ, implying that the total number of cardiomyocytes is set at birth. Analysis of cell division in the mammalian heart is complicated by cardiomyocyte binucleation shortly after birth, which makes it challenging to interpret traditional assays of cell turnover [Laflamme MA, Murray CE (2011) Nature 473(7347):326–335; Bergmann O, et al. (2009) Science 324(5923):98–102]. An elegant multi-isotope imaging-mass spectrometry technique recently calculated the low, discrete rate of cardiomyocyte generation in mice [Senyo SE, et al. (2013) Nature 493(7432):433–436], yet our cellular-level understanding of postnatal cardiomyogenesis remains limited. Herein, we provide a new line of evidence for the differentiated α-myosin heavy chain-expressing cardiomyocyte as the cell of origin of postnatal cardiomyogenesis using the “mosaic analysis with double markers” mouse model. We show limited, life-long, symmetric division of cardiomyocytes as a rare event that is evident in utero but significantly diminishes after the first month of life in mice; daughter cardiomyocytes divide very seldom, which this study is the first to demonstrate, to our knowledge. Furthermore, ligation of the left anterior descending coronary artery, which causes a myocardial infarction in the mosaic analysis with double-marker mice, did not increase the rate of cardiomyocyte division above the basal level for up to 4 wk after the injury. The clonal analysis described here provides direct evidence of postnatal mammalian cardiomyogenesis.
AU - Ali, Shah
AU - Hippenmeyer, Simon
AU - Saadat, Lily
AU - Luo, Liqun
AU - Weissman, Irving
AU - Ardehali, Reza
ID - 2020
IS - 24
JF - PNAS
TI - Existing cardiomyocytes generate cardiomyocytes at a low rate after birth in mice
VL - 111
ER -
TY - JOUR
AB - Neurotrophins regulate diverse aspects of neuronal development and plasticity, but their precise in vivo functions during neural circuit assembly in the central brain remain unclear. We show that the neurotrophin receptor tropomyosin-related kinase C (TrkC) is required for dendritic growth and branching of mouse cerebellar Purkinje cells. Sparse TrkC knockout reduced dendrite complexity, but global Purkinje cell knockout had no effect. Removal of the TrkC ligand neurotrophin-3 (NT-3) from cerebellar granule cells, which provide major afferent input to developing Purkinje cell dendrites, rescued the dendrite defects caused by sparse TrkC disruption in Purkinje cells. Our data demonstrate that NT-3 from presynaptic neurons (granule cells) is required for TrkC-dependent competitive dendrite morphogenesis in postsynaptic neurons (Purkinje cells)—a previously unknown mechanism of neural circuit development.
AU - William, Joo
AU - Hippenmeyer, Simon
AU - Luo, Liqun
ID - 2021
IS - 6209
JF - Science
TI - Dendrite morphogenesis depends on relative levels of NT-3/TrkC signaling
VL - 346
ER -
TY - CONF
AB - We present a general framework for applying machine-learning algorithms to the verification of Markov decision processes (MDPs). The primary goal of these techniques is to improve performance by avoiding an exhaustive exploration of the state space. Our framework focuses on probabilistic reachability, which is a core property for verification, and is illustrated through two distinct instantiations. The first assumes that full knowledge of the MDP is available, and performs a heuristic-driven partial exploration of the model, yielding precise lower and upper bounds on the required probability. The second tackles the case where we may only sample the MDP, and yields probabilistic guarantees, again in terms of both the lower and upper bounds, which provides efficient stopping criteria for the approximation. The latter is the first extension of statistical model checking for unbounded properties inMDPs. In contrast with other related techniques, our approach is not restricted to time-bounded (finite-horizon) or discounted properties, nor does it assume any particular properties of the MDP. We also show how our methods extend to LTL objectives. We present experimental results showing the performance of our framework on several examples.
AU - Brázdil, Tomáš
AU - Chatterjee, Krishnendu
AU - Chmelik, Martin
AU - Forejt, Vojtěch
AU - Kretinsky, Jan
AU - Kwiatkowska, Marta
AU - Parker, David
AU - Ujma, Mateusz
ED - Cassez, Franck
ED - Raskin, Jean-François
ID - 2027
T2 - Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics)
TI - Verification of markov decision processes using learning algorithms
VL - 8837
ER -
TY - JOUR
AB - A puzzling property of synaptic transmission, originally established at the neuromuscular junction, is that the time course of transmitter release is independent of the extracellular Ca2+ concentration ([Ca2+]o), whereas the rate of release is highly [Ca2+]o-dependent. Here, we examine the time course of release at inhibitory basket cell-Purkinje cell synapses and show that it is independent of [Ca2+]o. Modeling of Ca2+-dependent transmitter release suggests that the invariant time course of release critically depends on tight coupling between Ca2+ channels and release sensors. Experiments with exogenous Ca2+ chelators reveal that channel-sensor coupling at basket cell-Purkinje cell synapses is very tight, with a mean distance of 10–20 nm. Thus, tight channel-sensor coupling provides a mechanistic explanation for the apparent [Ca2+]o independence of the time course of release.
AU - Arai, Itaru
AU - Jonas, Peter M
ID - 2031
JF - eLife
TI - Nanodomain coupling explains Ca^2+ independence of transmitter release time course at a fast central synapse
VL - 3
ER -
TY - JOUR
AB - The yeast Rab5 homologue, Vps21p, is known to be involved both in the vacuolar protein sorting (VPS) pathway from the trans-Golgi network to the vacuole, and in the endocytic pathway from the plasma membrane to the vacuole. However, the intracellular location at which these two pathways converge remains unclear. In addition, the endocytic pathway is not completely blocked in yeast cells lacking all Rab5 genes, suggesting the existence of an unidentified route that bypasses the Rab5-dependent endocytic pathway. Here we show that convergence of the endocytic and VPS pathways occurs upstream of the requirement for Vps21p in these pathways. We also identify a previously unidentified endocytic pathway mediated by the AP-3 complex. Importantly, the AP-3-mediated pathway appears mostly intact in Rab5-disrupted cells, and thus works as an alternative route to the vacuole/lysosome. We propose that the endocytic traffic branches into two routes to reach the vacuole: a Rab5-dependent VPS pathway and a Rab5-independent AP-3-mediated pathway.
AU - Toshima, Junko
AU - Nishinoaki, Show
AU - Sato, Yoshifumi
AU - Yamamoto, Wataru
AU - Furukawa, Daiki
AU - Siekhaus, Daria E
AU - Sawaguchi, Akira
AU - Toshima, Jiro
ID - 2024
JF - Nature Communications
TI - Bifurcation of the endocytic pathway into Rab5-dependent and -independent transport to the vacuole
VL - 5
ER -
TY - JOUR
AB - Understanding the dynamics of noisy neurons remains an important challenge in neuroscience. Here, we describe a simple probabilistic model that accurately describes the firing behavior in a large class (type II) of neurons. To demonstrate the usefulness of this model, we show how it accurately predicts the interspike interval (ISI) distributions, bursting patterns and mean firing rates found by: (1) simulations of the classic Hodgkin-Huxley model with channel noise, (2) experimental data from squid giant axon with a noisy input current and (3) experimental data on noisy firing from a neuron within the suprachiasmatic nucleus (SCN). This simple model has 6 parameters, however, in some cases, two of these parameters are coupled and only 5 parameters account for much of the known behavior. From these parameters, many properties of spiking can be found through simple calculation. Thus, we show how the complex effects of noise can be understood through a simple and general probabilistic model.
AU - Bodova, Katarina
AU - Paydarfar, David
AU - Forger, Daniel
ID - 2028
JF - Journal of Theoretical Biology
TI - Characterizing spiking in noisy type II neurons
VL - 365
ER -
TY - CONF
AB - We present a tool for translating LTL formulae into deterministic ω-automata. It is the first tool that covers the whole LTL that does not use Safra’s determinization or any of its variants. This leads to smaller automata. There are several outputs of the tool: firstly, deterministic Rabin automata, which are the standard input for probabilistic model checking, e.g. for the probabilistic model-checker PRISM; secondly, deterministic generalized Rabin automata, which can also be used for probabilistic model checking and are sometimes by orders of magnitude smaller. We also link our tool to PRISM and show that this leads to a significant speed-up of probabilistic LTL model checking, especially with the generalized Rabin automata.
AU - Komárková, Zuzana
AU - Kretinsky, Jan
ED - Cassez, Franck
ED - Raskin, Jean-François
ID - 2026
T2 - Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics)
TI - Rabinizer 3: Safraless translation of ltl to small deterministic automata
VL - 8837
ER -
TY - JOUR
AB - Spin-wave theory is a key ingredient in our comprehension of quantum spin systems, and is used successfully for understanding a wide range of magnetic phenomena, including magnon condensation and stability of patterns in dipolar systems. Nevertheless, several decades of research failed to establish the validity of spin-wave theory rigorously, even for the simplest models of quantum spins. A rigorous justification of the method for the three-dimensional quantum Heisenberg ferromagnet at low temperatures is presented here. We derive sharp bounds on its free energy by combining a bosonic formulation of the model introduced by Holstein and Primakoff with probabilistic estimates and operator inequalities.
AU - Correggi, Michele
AU - Giuliani, Alessandro
AU - Seiringer, Robert
ID - 2029
IS - 2
JF - EPL
TI - Validity of spin-wave theory for the quantum Heisenberg model
VL - 108
ER -
TY - CONF
AB - The learning with privileged information setting has recently attracted a lot of attention within the machine learning community, as it allows the integration of additional knowledge into the training process of a classifier, even when this comes in the form of a data modality that is not available at test time. Here, we show that privileged information can naturally be treated as noise in the latent function of a Gaussian process classifier (GPC). That is, in contrast to the standard GPC setting, the latent function is not just a nuisance but a feature: it becomes a natural measure of confidence about the training data by modulating the slope of the GPC probit likelihood function. Extensive experiments on public datasets show that the proposed GPC method using privileged noise, called GPC+, improves over a standard GPC without privileged knowledge, and also over the current state-of-the-art SVM-based method, SVM+. Moreover, we show that advanced neural networks and deep learning methods can be compressed as privileged information.
AU - Hernandez Lobato, Daniel
AU - Sharmanska, Viktoriia
AU - Kersting, Kristian
AU - Lampert, Christoph
AU - Quadrianto, Novi
ID - 2033
IS - January
T2 - Advances in Neural Information Processing Systems
TI - Mind the nuisance: Gaussian process classification using privileged noise
VL - 1
ER -
TY - JOUR
AB - As light-based control of fundamental signaling pathways is becoming a reality, the field of optogenetics is rapidly moving beyond neuroscience. We have recently developed receptor tyrosine kinases that are activated by light and control cell proliferation, epithelial–mesenchymal transition, and angiogenic sprouting—cell behaviors central to cancer progression.
AU - Inglés Prieto, Álvaro
AU - Gschaider-Reichhart, Eva
AU - Schelch, Karin
AU - Janovjak, Harald L
AU - Grusch, Michael
ID - 2032
IS - 4
JF - Molecular and Cellular Oncology
TI - The optogenetic promise for oncology: Episode I
VL - 1
ER -
TY - CONF
AB - We introduce and study a new notion of enhanced chosen-ciphertext security (ECCA) for public-key encryption. Loosely speaking, in the ECCA security experiment, the decryption oracle provided to the adversary is augmented to return not only the output of the decryption algorithm on a queried ciphertext but also of a randomness-recovery algorithm associated to the scheme. Our results mainly concern the case where the randomness-recovery algorithm is efficient. We provide constructions of ECCA-secure encryption from adaptive trapdoor functions as defined by Kiltz et al. (EUROCRYPT 2010), resulting in ECCA encryption from standard number-theoretic assumptions. We then give two applications of ECCA-secure encryption: (1) We use it as a unifying concept in showing equivalence of adaptive trapdoor functions and tag-based adaptive trapdoor functions, resolving an open question of Kiltz et al. (2) We show that ECCA-secure encryption can be used to securely realize an approach to public-key encryption with non-interactive opening (PKENO) originally suggested by Damgård and Thorbek (EUROCRYPT 2007), resulting in new and practical PKENO schemes quite different from those in prior work. Our results demonstrate that ECCA security is of both practical and theoretical interest.
AU - Dachman Soled, Dana
AU - Fuchsbauer, Georg
AU - Mohassel, Payman
AU - O’Neill, Adam
ED - Krawczyk, Hugo
ID - 2045
T2 - Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics)
TI - Enhanced chosen-ciphertext security and applications
VL - 8383
ER -
TY - JOUR
AB - Background: CRISPR is a microbial immune system likely to be involved in host-parasite coevolution. It functions using target sequences encoded by the bacterial genome, which interfere with invading nucleic acids using a homology-dependent system. The system also requires protospacer associated motifs (PAMs), short motifs close to the target sequence that are required for interference in CRISPR types I and II. Here, we investigate whether PAMs are depleted in phage genomes due to selection pressure to escape recognition.Results: To this end, we analyzed two data sets. Phages infecting all bacterial hosts were analyzed first, followed by a detailed analysis of phages infecting the genus Streptococcus, where PAMs are best understood. We use two different measures of motif underrepresentation that control for codon bias and the frequency of submotifs. We compare phages infecting species with a particular CRISPR type to those infecting species without that type. Since only known PAMs were investigated, the analysis is restricted to CRISPR types I-C and I-E and in Streptococcus to types I-C and II. We found evidence for PAM depletion in Streptococcus phages infecting hosts with CRISPR type I-C, in Vibrio phages infecting hosts with CRISPR type I-E and in Streptococcus thermopilus phages infecting hosts with type II-A, known as CRISPR3.Conclusions: The observed motif depletion in phages with hosts having CRISPR can be attributed to selection rather than to mutational bias, as mutational bias should affect the phages of all hosts. This observation implies that the CRISPR system has been efficient in the groups discussed here.
AU - Kupczok, Anne
AU - Bollback, Jonathan P
ID - 2042
IS - 1
JF - BMC Genomics
TI - Motif depletion in bacteriophages infecting hosts with CRISPR systems
VL - 15
ER -
TY - CONF
AB - Persistent homology is a popular and powerful tool for capturing topological features of data. Advances in algorithms for computing persistent homology have reduced the computation time drastically – as long as the algorithm does not exhaust the available memory. Following up on a recently presented parallel method for persistence computation on shared memory systems [1], we demonstrate that a simple adaption of the standard reduction algorithm leads to a variant for distributed systems. Our algorithmic design ensures that the data is distributed over the nodes without redundancy; this permits the computation of much larger instances than on a single machine. Moreover, we observe that the parallelism at least compensates for the overhead caused by communication between nodes, and often even speeds up the computation compared to sequential and even parallel shared memory algorithms. In our experiments, we were able to compute the persistent homology of filtrations with more than a billion (109) elements within seconds on a cluster with 32 nodes using less than 6GB of memory per node.
AU - Bauer, Ulrich
AU - Kerber, Michael
AU - Reininghaus, Jan
ED - McGeoch, Catherine
ED - Meyer, Ulrich
ID - 2043
T2 - Proceedings of the Workshop on Algorithm Engineering and Experiments
TI - Distributed computation of persistent homology
ER -
TY - JOUR
AB - The hippocampus mediates several higher brain functions, such as learning, memory, and spatial coding. The input region of the hippocampus, the dentate gyrus, plays a critical role in these processes. Several lines of evidence suggest that the dentate gyrus acts as a preprocessor of incoming information, preparing it for subsequent processing in CA3. For example, the dentate gyrus converts input from the entorhinal cortex, where cells have multiple spatial fields, into the spatially more specific place cell activity characteristic of the CA3 region. Furthermore, the dentate gyrus is involved in pattern separation, transforming relatively similar input patterns into substantially different output patterns. Finally, the dentate gyrus produces a very sparse coding scheme in which only a very small fraction of neurons are active at any one time.
AU - Jonas, Peter M
AU - Lisman, John
ID - 2041
JF - Frontiers in Neural Circuits
TI - Structure, function and plasticity of hippocampal dentate gyrus microcircuits
VL - 8
ER -
TY - CHAP
AB - We present a parallel algorithm for computing the persistent homology of a filtered chain complex. Our approach differs from the commonly used reduction algorithm by first computing persistence pairs within local chunks, then simplifying the unpaired columns, and finally applying standard reduction on the simplified matrix. The approach generalizes a technique by Günther et al., which uses discrete Morse Theory to compute persistence; we derive the same worst-case complexity bound in a more general context. The algorithm employs several practical optimization techniques, which are of independent interest. Our sequential implementation of the algorithm is competitive with state-of-the-art methods, and we further improve the performance through parallel computation.
AU - Bauer, Ulrich
AU - Kerber, Michael
AU - Reininghaus, Jan
ED - Bremer, Peer-Timo
ED - Hotz, Ingrid
ED - Pascucci, Valerio
ED - Peikert, Ronald
ID - 2044
T2 - Topological Methods in Data Analysis and Visualization III
TI - Clear and Compress: Computing Persistent Homology in Chunks
ER -
TY - JOUR
AB - Development requires tissue growth as well as cell diversification. To address how these processes are coordinated, we analyzed the development of molecularly distinct domains of neural progenitors in the mouse and chick neural tube. We show that during development, these domains undergo changes in size that do not scale with changes in overall tissue size. Our data show that domain proportions are first established by opposing morphogen gradients and subsequently controlled by domain-specific regulation of differentiation rate but not differences in proliferation rate. Regulation of differentiation rate is key to maintaining domain proportions while accommodating both intra- and interspecies variations in size. Thus, the sequential control of progenitor specification and differentiation elaborates pattern without requiring that signaling gradients grow as tissues expand.
AU - Kicheva, Anna
AU - Bollenbach, Mark Tobias
AU - Ribeiro, Ana
AU - Pérez Valle, Helena
AU - Lovell Badge, Robin
AU - Episkopou, Vasso
AU - Briscoe, James
ID - 2040
IS - 6204
JF - Science
TI - Coordination of progenitor specification and growth in mouse and chick spinal cord
VL - 345
ER -
TY - CONF
AB - Following the publication of an attack on genome-wide association studies (GWAS) data proposed by Homer et al., considerable attention has been given to developing methods for releasing GWAS data in a privacy-preserving way. Here, we develop an end-to-end differentially private method for solving regression problems with convex penalty functions and selecting the penalty parameters by cross-validation. In particular, we focus on penalized logistic regression with elastic-net regularization, a method widely used to in GWAS analyses to identify disease-causing genes. We show how a differentially private procedure for penalized logistic regression with elastic-net regularization can be applied to the analysis of GWAS data and evaluate our method’s performance.
AU - Yu, Fei
AU - Rybar, Michal
AU - Uhler, Caroline
AU - Fienberg, Stephen
ED - Domingo Ferrer, Josep
ID - 2047
T2 - Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics)
TI - Differentially-private logistic regression for detecting multiple-SNP association in GWAS databases
VL - 8744
ER -
TY - CONF
AB - In contrast to the usual understanding of probabilistic systems as stochastic processes, recently these systems have also been regarded as transformers of probabilities. In this paper, we give a natural definition of strong bisimulation for probabilistic systems corresponding to this view that treats probability distributions as first-class citizens. Our definition applies in the same way to discrete systems as well as to systems with uncountable state and action spaces. Several examples demonstrate that our definition refines the understanding of behavioural equivalences of probabilistic systems. In particular, it solves a longstanding open problem concerning the representation of memoryless continuous time by memoryfull continuous time. Finally, we give algorithms for computing this bisimulation not only for finite but also for classes of uncountably infinite systems.
AU - Hermanns, Holger
AU - Krčál, Jan
AU - Kretinsky, Jan
ED - Baldan, Paolo
ED - Gorla, Daniele
ID - 2053
T2 - Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics)
TI - Probabilistic bisimulation: Naturally on distributions
VL - 8704
ER -
TY - CONF
AB - A standard technique for solving the parameterized model checking problem is to reduce it to the classic model checking problem of finitely many finite-state systems. This work considers some of the theoretical power and limitations of this technique. We focus on concurrent systems in which processes communicate via pairwise rendezvous, as well as the special cases of disjunctive guards and token passing; specifications are expressed in indexed temporal logic without the next operator; and the underlying network topologies are generated by suitable Monadic Second Order Logic formulas and graph operations. First, we settle the exact computational complexity of the parameterized model checking problem for some of our concurrent systems, and establish new decidability results for others. Second, we consider the cases that model checking the parameterized system can be reduced to model checking some fixed number of processes, the number is known as a cutoff. We provide many cases for when such cutoffs can be computed, establish lower bounds on the size of such cutoffs, and identify cases where no cutoff exists. Third, we consider cases for which the parameterized system is equivalent to a single finite-state system (more precisely a Büchi word automaton), and establish tight bounds on the sizes of such automata.
AU - Aminof, Benjamin
AU - Kotek, Tomer
AU - Rubin, Sacha
AU - Spegni, Francesco
AU - Veith, Helmut
ED - Baldan, Paolo
ED - Gorla, Daniele
ID - 2052
T2 - Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics)
TI - Parameterized model checking of rendezvous systems
VL - 8704
ER -
TY - CONF
AB - We introduce policy-based signatures (PBS), where a signer can only sign messages conforming to some authority-specified policy. The main requirements are unforgeability and privacy, the latter meaning that signatures not reveal the policy. PBS offers value along two fronts: (1) On the practical side, they allow a corporation to control what messages its employees can sign under the corporate key. (2) On the theoretical side, they unify existing work, capturing other forms of signatures as special cases or allowing them to be easily built. Our work focuses on definitions of PBS, proofs that this challenging primitive is realizable for arbitrary policies, efficient constructions for specific policies, and a few representative applications.
AU - Bellare, Mihir
AU - Fuchsbauer, Georg
ED - Krawczyk, Hugo
ID - 2046
T2 - Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics)
TI - Policy-based signatures
VL - 8383
ER -
TY - JOUR
AB - The flow instability and further transition to turbulence in a toroidal pipe (torus) with curvature ratio (tube-to-coiling diameter) 0.049 is investigated experimentally. The flow inside the toroidal pipe is driven by a steel sphere fitted to the inner pipe diameter. The sphere is moved with constant azimuthal velocity from outside the torus by a moving magnet. The experiment is designed to investigate curved pipe flow by optical measurement techniques. Using stereoscopic particle image velocimetry, laser Doppler velocimetry and pressure drop measurements, the flow is measured for Reynolds numbers ranging from 1000 to 15 000. Time- and space-resolved velocity fields are obtained and analysed. The steady axisymmetric basic flow is strongly influenced by centrifugal effects. On an increase of the Reynolds number we find a sequence of bifurcations. For Re=4075±2% a supercritical bifurcation to an oscillatory flow is found in which waves travel in the streamwise direction with a phase velocity slightly faster than the mean flow. The oscillatory flow is superseded by a presumably quasi-periodic flow at a further increase of the Reynolds number before turbulence sets in. The results are found to be compatible, in general, with earlier experimental and numerical investigations on transition to turbulence in helical and curved pipes. However, important aspects of the bifurcation scenario differ considerably.
AU - Kühnen, Jakob
AU - Holzner, Markus
AU - Hof, Björn
AU - Kuhlmann, Hendrik
ID - 2050
JF - Journal of Fluid Mechanics
TI - Experimental investigation of transitional flow in a toroidal pipe
VL - 738
ER -
TY - JOUR
AB - Plant embryogenesis is regulated by differential distribution of the plant hormone auxin. However, the cells establishing these gradients during microspore embryogenesis remain to be identified. For the first time, we describe, using the DR5 or DR5rev reporter gene systems, the GFP- and GUS-based auxin biosensors to monitor auxin during Brassica napus androgenesis at cellular resolution in the initial stages. Our study provides evidence that the distribution of auxin changes during embryo development and depends on the temperature-inducible in vitro culture conditions. For this, microspores (mcs) were induced to embryogenesis by heat treatment and then subjected to genetic modification via Agrobacterium tumefaciens. The duration of high temperature treatment had a significant influence on auxin distribution in isolated and in vitro-cultured microspores and on microspore-derived embryo development. In the “mild” heat-treated (1 day at 32 °C) mcs, auxin localized in a polar way already at the uni-nucleate microspore, which was critical for the initiation of embryos with suspensor-like structure. Assuming a mean mcs radius of 20 μm, endogenous auxin content in a single cell corresponded to concentration of 1.01 μM. In mcs subjected to a prolonged heat (5 days at 32 °C), although auxin concentration increased dozen times, auxin polarization was set up at a few-celled pro-embryos without suspensor. Those embryos were enclosed in the outer wall called the exine. The exine rupture was accompanied by the auxin gradient polarization. Relative quantitative estimation of auxin, using time-lapse imaging, revealed that primordia possess up to 1.3-fold higher amounts than those found in the root apices of transgenic MDEs in the presence of exogenous auxin. Our results show, for the first time, which concentration of endogenous auxin coincides with the first cell division and how the high temperature interplays with auxin, by what affects delay early establishing microspore polarity. Moreover, we present how the local auxin accumulation demonstrates the apical–basal axis formation of the androgenic embryo and directs the axiality of the adult haploid plant.
AU - Dubas, Ewa
AU - Moravčíková, Jana
AU - Libantová, Jana
AU - Matušíková, Ildikó
AU - Benková, Eva
AU - Zur, Iwona
AU - Krzewska, Monika
ID - 2059
IS - 5
JF - Protoplasma
TI - The influence of heat stress on auxin distribution in transgenic B napus microspores and microspore derived embryos
VL - 251
ER -
TY - JOUR
AB - The success story of fast-spiking, parvalbumin-positive (PV+) GABAergic interneurons (GABA, γ-aminobutyric acid) in the mammalian central nervous system is noteworthy. In 1995, the properties of these interneurons were completely unknown. Twenty years later, thanks to the massive use of subcellular patch-clamp techniques, simultaneous multiple-cell recording, optogenetics, in vivo measurements, and computational approaches, our knowledge about PV+ interneurons became more extensive than for several types of pyramidal neurons. These findings have implications beyond the “small world” of basic research on GABAergic cells. For example, the results provide a first proof of principle that neuroscientists might be able to close the gaps between the molecular, cellular, network, and behavioral levels, representing one of the main challenges at the present time. Furthermore, the results may form the basis for PV+ interneurons as therapeutic targets for brain disease in the future. However, much needs to be learned about the basic function of these interneurons before clinical neuroscientists will be able to use PV+ interneurons for therapeutic purposes.
AU - Hu, Hua
AU - Gan, Jian
AU - Jonas, Peter M
ID - 2062
IS - 6196
JF - Science
TI - Fast-spiking parvalbumin^+ GABAergic interneurons: From cellular design to microcircuit function
VL - 345
ER -
TY - CONF
AB - We present a method for smoothly blending between existing liquid animations. We introduce a semi-automatic method for matching two existing liquid animations, which we use to create new fluid motion that plausibly interpolates the input. Our contributions include a new space-time non-rigid iterative closest point algorithm that incorporates user guidance, a subsampling technique for efficient registration of meshes with millions of vertices, and a fast surface extraction algorithm that produces 3D triangle meshes from a 4D space-time surface. Our technique can be used to instantly create hundreds of new simulations, or to interactively explore complex parameter spaces. Our method is guaranteed to produce output that does not deviate from the input animations, and it generalizes to multiple dimensions. Because our method runs at interactive rates after the initial precomputation step, it has potential applications in games and training simulations.
AU - Raveendran, Karthik
AU - Wojtan, Christopher J
AU - Thuerey, Nils
AU - Türk, Greg
ID - 2058
IS - 4
T2 - ACM Transactions on Graphics
TI - Blending liquids
VL - 33
ER -
TY - CONF
AB - In the past few years, a lot of attention has been devoted to multimedia indexing by fusing multimodal informations. Two kinds of fusion schemes are generally considered: The early fusion and the late fusion. We focus on late classifier fusion, where one combines the scores of each modality at the decision level. To tackle this problem, we investigate a recent and elegant well-founded quadratic program named MinCq coming from the machine learning PAC-Bayesian theory. MinCq looks for the weighted combination, over a set of real-valued functions seen as voters, leading to the lowest misclassification rate, while maximizing the voters’ diversity. We propose an extension of MinCq tailored to multimedia indexing. Our method is based on an order-preserving pairwise loss adapted to ranking that allows us to improve Mean Averaged Precision measure while taking into account the diversity of the voters that we want to fuse. We provide evidence that this method is naturally adapted to late fusion procedures and confirm the good behavior of our approach on the challenging PASCAL VOC’07 benchmark.
AU - Morvant, Emilie
AU - Habrard, Amaury
AU - Ayache, Stéphane
ID - 2057
T2 - Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics)
TI - Majority vote of diverse classifiers for late fusion
VL - 8621
ER -
TY - JOUR
AB - We consider a continuous-time Markov chain (CTMC) whose state space is partitioned into aggregates, and each aggregate is assigned a probability measure. A sufficient condition for defining a CTMC over the aggregates is presented as a variant of weak lumpability, which also characterizes that the measure over the original process can be recovered from that of the aggregated one. We show how the applicability of de-aggregation depends on the initial distribution. The application section is devoted to illustrate how the developed theory aids in reducing CTMC models of biochemical systems particularly in connection to protein-protein interactions. We assume that the model is written by a biologist in form of site-graph-rewrite rules. Site-graph-rewrite rules compactly express that, often, only a local context of a protein (instead of a full molecular species) needs to be in a certain configuration in order to trigger a reaction event. This observation leads to suitable aggregate Markov chains with smaller state spaces, thereby providing sufficient reduction in computational complexity. This is further exemplified in two case studies: simple unbounded polymerization and early EGFR/insulin crosstalk.
AU - Ganguly, Arnab
AU - Petrov, Tatjana
AU - Koeppl, Heinz
ID - 2056
IS - 3
JF - Journal of Mathematical Biology
TI - Markov chain aggregation and its applications to combinatorial reaction networks
VL - 69
ER -
TY - JOUR
AB - Development of cambium and its activity is important for our knowledge of the mechanism of secondary growth. Arabidopsis thaliana emerges as a good model plant for such a kind of study. Thus, this paper reports on cellular events taking place in the interfascicular regions of inflorescence stems of A. thaliana, leading to the development of interfascicular cambium from differentiated interfascicular parenchyma cells (IPC). These events are as follows: appearance of auxin accumulation, PIN1 gene expression, polar PIN1 protein localization in the basal plasma membrane and periclinal divisions. Distribution of auxin was observed to be higher in differentiating into cambium parenchyma cells compared to cells within the pith and cortex. Expression of PIN1 in IPC was always preceded by auxin accumulation. Basal localization of PIN1 was already established in the cells prior to their periclinal division. These cellular events initiated within parenchyma cells adjacent to the vascular bundles and successively extended from that point towards the middle region of the interfascicular area, located between neighboring vascular bundles. The final consequence of which was the closure of the cambial ring within the stem. Changes in the chemical composition of IPC walls were also detected and included changes of pectic epitopes, xyloglucans (XG) and extensins rich in hydroxyproline (HRGPs). In summary, results presented in this paper describe interfascicular cambium ontogenesis in terms of successive cellular events in the interfascicular regions of inflorescence stems of Arabidopsis.
AU - Mazur, Ewa
AU - Kurczyñska, Ewa
AU - Friml, Jiří
ID - 2061
IS - 5
JF - Protoplasma
TI - Cellular events during interfascicular cambium ontogenesis in inflorescence stems of Arabidopsis
VL - 251
ER -
TY - JOUR
AB - We examined the synaptic structure, quantity, and distribution of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)- and N-methyl-D-aspartate (NMDA)-type glutamate receptors (AMPARs and NMDARs, respectively) in rat cochlear nuclei by a highly sensitive freeze-fracture replica labeling technique. Four excitatory synapses formed by two distinct inputs, auditory nerve (AN) and parallel fibers (PF), on different cell types were analyzed. These excitatory synapse types included AN synapses on bushy cells (AN-BC synapses) and fusiform cells (AN-FC synapses) and PF synapses on FC (PF-FC synapses) and cartwheel cell spines (PF-CwC synapses). Immunogold labeling revealed differences in synaptic structure as well as AMPAR and NMDAR number and/or density in both AN and PF synapses, indicating a target-dependent organization. The immunogold receptor labeling also identified differences in the synaptic organization of FCs based on AN or PF connections, indicating an input-dependent organization in FCs. Among the four excitatory synapse types, the AN-BC synapses were the smallest and had the most densely packed intramembrane particles (IMPs), whereas the PF-CwC synapses were the largest and had sparsely packed IMPs. All four synapse types showed positive correlations between the IMP-cluster area and the AMPAR number, indicating a common intrasynapse-type relationship for glutamatergic synapses. Immunogold particles for AMPARs were distributed over the entire area of individual AN synapses; PF synapses often showed synaptic areas devoid of labeling. The gold-labeling for NMDARs occurred in a mosaic fashion, with less positive correlations between the IMP-cluster area and the NMDAR number. Our observations reveal target- and input-dependent features in the structure, number, and organization of AMPARs and NMDARs in AN and PF synapses.
AU - Rubio, Maía
AU - Fukazawa, Yugo
AU - Kamasawa, Naomi
AU - Clarkson, Cheryl
AU - Molnár, Elek
AU - Shigemoto, Ryuichi
ID - 2064
IS - 18
JF - Journal of Comparative Neurology
TI - Target- and input-dependent organization of AMPA and NMDA receptors in synaptic connections of the cochlear nucleus
VL - 522
ER -
TY - CONF
AB - We define a simple, explicit map sending a morphism f : M → N of pointwise finite dimensional persistence modules to a matching between the barcodes of M and N. Our main result is that, in a precise sense, the quality of this matching is tightly controlled by the lengths of the longest intervals in the barcodes of ker f and coker f . As an immediate corollary, we obtain a new proof of the algebraic stability theorem for persistence barcodes [5, 9], a fundamental result in the theory of persistent homology. In contrast to previous proofs, ours shows explicitly how a δ-interleaving morphism between two persistence modules induces a δ-matching between the barcodes of the two modules. Our main result also specializes to a structure theorem for submodules and quotients of persistence modules. Copyright is held by the owner/author(s).
AU - Bauer, Ulrich
AU - Lesnick, Michael
ID - 2153
T2 - Proceedings of the Annual Symposium on Computational Geometry
TI - Induced matchings of barcodes and the algebraic stability of persistence
ER -
TY - JOUR
AB - A result of Boros and Füredi (d = 2) and of Bárány (arbitrary d) asserts that for every d there exists cd > 0 such that for every n-point set P ⊂ ℝd, some point of ℝd is covered by at least (Formula presented.) of the d-simplices spanned by the points of P. The largest possible value of cd has been the subject of ongoing research. Recently Gromov improved the existing lower bounds considerably by introducing a new, topological proof method. We provide an exposition of the combinatorial component of Gromov's approach, in terms accessible to combinatorialists and discrete geometers, and we investigate the limits of his method. In particular, we give tighter bounds on the cofilling profiles for the (n - 1)-simplex. These bounds yield a minor improvement over Gromov's lower bounds on cd for large d, but they also show that the room for further improvement through the cofilling profiles alone is quite small. We also prove a slightly better lower bound for c3 by an approach using an additional structure besides the cofilling profiles. We formulate a combinatorial extremal problem whose solution might perhaps lead to a tight lower bound for cd.
AU - Matoušek, Jiří
AU - Wagner, Uli
ID - 2154
IS - 1
JF - Discrete & Computational Geometry
TI - On Gromov's method of selecting heavily covered points
VL - 52
ER -
TY - CONF
AB - We propose a metric for Reeb graphs, called the functional distortion distance. Under this distance, the Reeb graph is stable against small changes of input functions. At the same time, it remains discriminative at differentiating input functions. In particular, the main result is that the functional distortion distance between two Reeb graphs is bounded from below by the bottleneck distance between both the ordinary and extended persistence diagrams for appropriate dimensions. As an application of our results, we analyze a natural simplification scheme for Reeb graphs, and show that persistent features in Reeb graph remains persistent under simplification. Understanding the stability of important features of the Reeb graph under simplification is an interesting problem on its own right, and critical to the practical usage of Reeb graphs. Copyright is held by the owner/author(s).
AU - Bauer, Ulrich
AU - Ge, Xiaoyin
AU - Wang, Yusu
ID - 2156
T2 - Proceedings of the Annual Symposium on Computational Geometry
TI - Measuring distance between Reeb graphs
ER -
TY - CONF
AB - Given a finite set of points in Rn and a positive radius, we study the Čech, Delaunay-Čech, alpha, and wrap complexes as instances of a generalized discrete Morse theory. We prove that the latter three complexes are simple-homotopy equivalent. Our results have applications in topological data analysis and in the reconstruction of shapes from sampled data. Copyright is held by the owner/author(s).
AU - Bauer, Ulrich
AU - Edelsbrunner, Herbert
ID - 2155
T2 - Proceedings of the Annual Symposium on Computational Geometry
TI - The morse theory of Čech and Delaunay filtrations
ER -
TY - CONF
AB - Transfer learning has received a lot of attention in the machine learning community over the last years, and several effective algorithms have been developed. However, relatively little is known about their theoretical properties, especially in the setting of lifelong learning, where the goal is to transfer information to tasks for which no data have been observed so far. In this work we study lifelong learning from a theoretical perspective. Our main result is a PAC-Bayesian generalization bound that offers a unified view on existing paradigms for transfer learning, such as the transfer of parameters or the transfer of low-dimensional representations. We also use the bound to derive two principled lifelong learning algorithms, and we show that these yield results comparable with existing methods.
AU - Pentina, Anastasia
AU - Lampert, Christoph
ED - Xing, Eric
ED - Jebara, Tony
ID - 2160
TI - A PAC-Bayesian bound for Lifelong Learning
VL - 32
ER -
TY - JOUR
AB - Directional guidance of migrating cells is relatively well explored in the reductionist setting of cell culture experiments. Here spatial gradients of chemical cues as well as gradients of mechanical substrate characteristics prove sufficient to attract single cells as well as their collectives. How such gradients present and act in the context of an organism is far less clear. Here we review recent advances in understanding how guidance cues emerge and operate in the physiological context.
AU - Majumdar, Ritankar
AU - Sixt, Michael K
AU - Parent, Carole
ID - 2158
IS - 1
JF - Current Opinion in Cell Biology
TI - New paradigms in the establishment and maintenance of gradients during directed cell migration
VL - 30
ER -
TY - JOUR
AB - Neuronal ectopia, such as granule cell dispersion (GCD) in temporal lobe epilepsy (TLE), has been assumed to result from a migration defect during development. Indeed, recent studies reported that aberrant migration of neonatal-generated dentate granule cells (GCs) increased the risk to develop epilepsy later in life. On the contrary, in the present study, we show that fully differentiated GCs become motile following the induction of epileptiform activity, resulting in GCD. Hippocampal slice cultures from transgenic mice expressing green fluorescent protein in differentiated, but not in newly generated GCs, were incubated with the glutamate receptor agonist kainate (KA), which induced GC burst activity and GCD. Using real-time microscopy, we observed that KA-exposed, differentiated GCs translocated their cell bodies and changed their dendritic organization. As found in human TLE, KA application was associated with decreased expression of the extracellular matrix protein Reelin, particularly in hilar interneurons. Together these findings suggest that KA-induced motility of differentiated GCs contributes to the development of GCD and establish slice cultures as a model to study neuronal changes induced by epileptiform activity.
AU - Chai, Xuejun
AU - Münzner, Gert
AU - Zhao, Shanting
AU - Tinnes, Stefanie
AU - Kowalski, Janina
AU - Häussler, Ute
AU - Young, Christina
AU - Haas, Carola
AU - Frotscher, Michael
ID - 2164
IS - 8
JF - Cerebral Cortex
TI - Epilepsy-induced motility of differentiated neurons
VL - 24
ER -
TY - JOUR
AB - Many species have an essentially continuous distribution in space, in which there are no natural divisions between randomly mating subpopulations. Yet, the standard approach to modelling these populations is to impose an arbitrary grid of demes, adjusting deme sizes and migration rates in an attempt to capture the important features of the population. Such indirect methods are required because of the failure of the classical models of isolation by distance, which have been shown to have major technical flaws. A recently introduced model of extinction and recolonisation in two dimensions solves these technical problems, and provides a rigorous technical foundation for the study of populations evolving in a spatial continuum. The coalescent process for this model is simply stated, but direct simulation is very inefficient for large neighbourhood sizes. We present efficient and exact algorithms to simulate this coalescent process for arbitrary sample sizes and numbers of loci, and analyse these algorithms in detail.
AU - Kelleher, Jerome
AU - Etheridge, Alison
AU - Barton, Nicholas H
ID - 2168
JF - Theoretical Population Biology
TI - Coalescent simulation in continuous space: Algorithms for large neighbourhood size
VL - 95
ER -
TY - JOUR
AU - Barton, Nicholas H
AU - Novak, Sebastian
AU - Paixao, Tiago
ID - 2169
IS - 29
JF - PNAS
TI - Diverse forms of selection in evolution and computer science
VL - 111
ER -
TY - CONF
AB - We present LS-CRF, a new method for training cyclic Conditional Random Fields (CRFs) from large datasets that is inspired by classical closed-form expressions for the maximum likelihood parameters of a generative graphical model with tree topology. Training a CRF with LS-CRF requires only solving a set of independent regression problems, each of which can be solved efficiently in closed form or by an iterative solver. This makes LS-CRF orders of magnitude faster than classical CRF training based on probabilistic inference, and at the same time more flexible and easier to implement than other approximate techniques, such as pseudolikelihood or piecewise training. We apply LS-CRF to the task of semantic image segmentation, showing that it achieves on par accuracy to other training techniques at higher speed, thereby allowing efficient CRF training from very large training sets. For example, training a linearly parameterized pairwise CRF on 150,000 images requires less than one hour on a modern workstation.
AU - Kolesnikov, Alexander
AU - Guillaumin, Matthieu
AU - Ferrari, Vittorio
AU - Lampert, Christoph
ED - Fleet, David
ED - Pajdla, Tomas
ED - Schiele, Bernt
ED - Tuytelaars, Tinne
ID - 2171
IS - PART 3
T2 - Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics)
TI - Closed-form approximate CRF training for scalable image segmentation
VL - 8691
ER -
TY - CONF
AB - In this work we introduce a new approach to co-classification, i.e. the task of jointly classifying multiple, otherwise independent, data samples. The method we present, named CoConut, is based on the idea of adding a regularizer in the label space to encode certain priors on the resulting labelings. A regularizer that encourages labelings that are smooth across the test set, for instance, can be seen as a test-time variant of the cluster assumption, which has been proven useful at training time in semi-supervised learning. A regularizer that introduces a preference for certain class proportions can be regarded as a prior distribution on the class labels. CoConut can build on existing classifiers without making any assumptions on how they were obtained and without the need to re-train them. The use of a regularizer adds a new level of flexibility. It allows the integration of potentially new information at test time, even in other modalities than what the classifiers were trained on. We evaluate our framework on six datasets, reporting a clear performance gain in classification accuracy compared to the standard classification setup that predicts labels for each test sample separately.
AU - Khamis, Sameh
AU - Lampert, Christoph
ID - 2173
T2 - Proceedings of the British Machine Vision Conference 2014
TI - CoConut: Co-classification with output space regularization
ER -
TY - JOUR
AB - The cerebral cortex, the seat of our cognitive abilities, is composed of an intricate network of billions of excitatory projection and inhibitory interneurons. Postmitotic cortical neurons are generated by a diverse set of neural stem cell progenitors within dedicated zones and defined periods of neurogenesis during embryonic development. Disruptions in neurogenesis can lead to alterations in the neuronal cytoarchitecture, which is thought to represent a major underlying cause for several neurological disorders, including microcephaly, autism and epilepsy. Although a number of signaling pathways regulating neurogenesis have been described, the precise cellular and molecular mechanisms regulating the functional neural stem cell properties in cortical neurogenesis remain unclear. Here, we discuss the most up-to-date strategies to monitor the fundamental mechanistic parameters of neuronal progenitor proliferation, and recent advances deciphering the logic and dynamics of neurogenesis.
AU - Postiglione, Maria P
AU - Hippenmeyer, Simon
ID - 2175
IS - 3
JF - Future Neurology
TI - Monitoring neurogenesis in the cerebral cortex: an update
VL - 9
ER -
TY - CONF
AB - Fisher Kernels and Deep Learning were two developments with significant impact on large-scale object categorization in the last years. Both approaches were shown to achieve state-of-the-art results on large-scale object categorization datasets, such as ImageNet. Conceptually, however, they are perceived as very different and it is not uncommon for heated debates to spring up when advocates of both paradigms meet at conferences or workshops. In this work, we emphasize the similarities between both architectures rather than their differences and we argue that such a unified view allows us to transfer ideas from one domain to the other. As a concrete example we introduce a method for learning a support vector machine classifier with Fisher kernel at the same time as a task-specific data representation. We reinterpret the setting as a multi-layer feed forward network. Its final layer is the classifier, parameterized by a weight vector, and the two previous layers compute Fisher vectors, parameterized by the coefficients of a Gaussian mixture model. We introduce a gradient descent based learning algorithm that, in contrast to other feature learning techniques, is not just derived from intuition or biological analogy, but has a theoretical justification in the framework of statistical learning theory. Our experiments show that the new training procedure leads to significant improvements in classification accuracy while preserving the modularity and geometric interpretability of a support vector machine setup.
AU - Sydorov, Vladyslav
AU - Sakurada, Mayu
AU - Lampert, Christoph
ID - 2172
T2 - Proceedings of the IEEE Computer Society Conference on Computer Vision and Pattern Recognition
TI - Deep Fisher Kernels – End to end learning of the Fisher Kernel GMM parameters
ER -
TY - JOUR
AB - When polygenic traits are under stabilizing selection, many different combinations of alleles allow close adaptation to the optimum. If alleles have equal effects, all combinations that result in the same deviation from the optimum are equivalent. Furthermore, the genetic variance that is maintained by mutation-selection balance is 2μ/S per locus, where μ is the mutation rate and S the strength of stabilizing selection. In reality, alleles vary in their effects, making the fitness landscape asymmetric and complicating analysis of the equilibria. We show that that the resulting genetic variance depends on the fraction of alleles near fixation, which contribute by 2μ/S, and on the total mutational effects of alleles that are at intermediate frequency. The inpplayfi between stabilizing selection and mutation leads to a sharp transition: alleles with effects smaller than a threshold value of 2 remain polymorphic, whereas those with larger effects are fixed. The genetic load in equilibrium is less than for traits of equal effects, and the fitness equilibria are more similar. We find p the optimum is displaced, alleles with effects close to the threshold value sweep first, and their rate of increase is bounded by Long-term response leads in general to well-adapted traits, unlike the case of equal effects that often end up at a suboptimal fitness peak. However, the particular peaks to which the populations converge are extremely sensitive to the initial states and to the speed of the shift of the optimum trait value.
AU - De Vladar, Harold
AU - Barton, Nicholas H
ID - 2174
IS - 2
JF - Genetics
TI - Stability and response of polygenic traits to stabilizing selection and mutation
VL - 197
ER -
TY - JOUR
AB - We extend the proof of the local semicircle law for generalized Wigner matrices given in MR3068390 to the case when the matrix of variances has an eigenvalue -1. In particular, this result provides a short proof of the optimal local Marchenko-Pastur law at the hard edge (i.e. around zero) for sample covariance matrices X*X, where the variances of the entries of X may vary.
AU - Ajanki, Oskari H
AU - Erdös, László
AU - Krüger, Torben H
ID - 2179
JF - Electronic Communications in Probability
TI - Local semicircle law with imprimitive variance matrix
VL - 19
ER -
TY - JOUR
AB - Electron microscopy (EM) allows for the simultaneous visualization of all tissue components at high resolution. However, the extent to which conventional aldehyde fixation and ethanol dehydration of the tissue alter the fine structure of cells and organelles, thereby preventing detection of subtle structural changes induced by an experiment, has remained an issue. Attempts have been made to rapidly freeze tissue to preserve native ultrastructure. Shock-freezing of living tissue under high pressure (high-pressure freezing, HPF) followed by cryosubstitution of the tissue water avoids aldehyde fixation and dehydration in ethanol; the tissue water is immobilized in â ̂1/450 ms, and a close-to-native fine structure of cells, organelles and molecules is preserved. Here we describe a protocol for HPF that is useful to monitor ultrastructural changes associated with functional changes at synapses in the brain but can be applied to many other tissues as well. The procedure requires a high-pressure freezer and takes a minimum of 7 d but can be paused at several points.
AU - Studer, Daniel
AU - Zhao, Shanting
AU - Chai, Xuejun
AU - Jonas, Peter M
AU - Graber, Werner
AU - Nestel, Sigrun
AU - Frotscher, Michael
ID - 2176
IS - 6
JF - Nature Protocols
TI - Capture of activity-induced ultrastructural changes at synapses by high-pressure freezing of brain tissue
VL - 9
ER -
TY - JOUR
AB - We consider the three-state toric homogeneous Markov chain model (THMC) without loops and initial parameters. At time T, the size of the design matrix is 6 × 3 · 2T-1 and the convex hull of its columns is the model polytope. We study the behavior of this polytope for T ≥ 3 and we show that it is defined by 24 facets for all T ≥ 5. Moreover, we give a complete description of these facets. From this, we deduce that the toric ideal associated with the design matrix is generated by binomials of degree at most 6. Our proof is based on a result due to Sturmfels, who gave a bound on the degree of the generators of a toric ideal, provided the normality of the corresponding toric variety. In our setting, we established the normality of the toric variety associated to the THMC model by studying the geometric properties of the model polytope.
AU - Haws, David
AU - Martin Del Campo Sanchez, Abraham
AU - Takemura, Akimichi
AU - Yoshida, Ruriko
ID - 2178
IS - 1
JF - Beitrage zur Algebra und Geometrie
TI - Markov degree of the three-state toric homogeneous Markov chain model
VL - 55
ER -
TY - CONF
AB - We give evidence for the difficulty of computing Betti numbers of simplicial complexes over a finite field. We do this by reducing the rank computation for sparse matrices with to non-zero entries to computing Betti numbers of simplicial complexes consisting of at most a constant times to simplices. Together with the known reduction in the other direction, this implies that the two problems have the same computational complexity.
AU - Edelsbrunner, Herbert
AU - Parsa, Salman
ID - 2177
T2 - Proceedings of the Annual ACM-SIAM Symposium on Discrete Algorithms
TI - On the computational complexity of betti numbers reductions from matrix rank
ER -
TY - CONF
AB - We revisit the classical problem of converting an imperfect source of randomness into a usable cryptographic key. Assume that we have some cryptographic application P that expects a uniformly random m-bit key R and ensures that the best attack (in some complexity class) against P(R) has success probability at most δ. Our goal is to design a key-derivation function (KDF) h that converts any random source X of min-entropy k into a sufficiently "good" key h(X), guaranteeing that P(h(X)) has comparable security δ′ which is 'close' to δ. Seeded randomness extractors provide a generic way to solve this problem for all applications P, with resulting security δ′ = O(δ), provided that we start with entropy k ≥ m + 2 log (1/δ) - O(1). By a result of Radhakrishnan and Ta-Shma, this bound on k (called the "RT-bound") is also known to be tight in general. Unfortunately, in many situations the loss of 2 log (1/δ) bits of entropy is unacceptable. This motivates the study KDFs with less entropy waste by placing some restrictions on the source X or the application P. In this work we obtain the following new positive and negative results in this regard: - Efficient samplability of the source X does not help beat the RT-bound for general applications. This resolves the SRT (samplable RT) conjecture of Dachman-Soled et al. [DGKM12] in the affirmative, and also shows that the existence of computationally-secure extractors beating the RT-bound implies the existence of one-way functions. - We continue in the line of work initiated by Barak et al. [BDK+11] and construct new information-theoretic KDFs which beat the RT-bound for large but restricted classes of applications. Specifically, we design efficient KDFs that work for all unpredictability applications P (e.g., signatures, MACs, one-way functions, etc.) and can either: (1) extract all of the entropy k = m with a very modest security loss δ′ = O(δ·log (1/δ)), or alternatively, (2) achieve essentially optimal security δ′ = O(δ) with a very modest entropy loss k ≥ m + loglog (1/δ). In comparison, the best prior results from [BDK+11] for this class of applications would only guarantee δ′ = O(√δ) when k = m, and would need k ≥ m + log (1/δ) to get δ′ = O(δ). - The weaker bounds of [BDK+11] hold for a larger class of so-called "square- friendly" applications (which includes all unpredictability, but also some important indistinguishability, applications). Unfortunately, we show that these weaker bounds are tight for the larger class of applications. - We abstract out a clean, information-theoretic notion of (k,δ,δ′)- unpredictability extractors, which guarantee "induced" security δ′ for any δ-secure unpredictability application P, and characterize the parameters achievable for such unpredictability extractors. Of independent interest, we also relate this notion to the previously-known notion of (min-entropy) condensers, and improve the state-of-the-art parameters for such condensers.
AU - Dodis, Yevgeniy
AU - Pietrzak, Krzysztof Z
AU - Wichs, Daniel
ED - Nguyen, Phong
ED - Oswald, Elisabeth
ID - 2185
TI - Key derivation without entropy waste
VL - 8441
ER -
TY - JOUR
AB - Weighted majority votes allow one to combine the output of several classifiers or voters. MinCq is a recent algorithm for optimizing the weight of each voter based on the minimization of a theoretical bound over the risk of the vote with elegant PAC-Bayesian generalization guarantees. However, while it has demonstrated good performance when combining weak classifiers, MinCq cannot make use of the useful a priori knowledge that one may have when using a mixture of weak and strong voters. In this paper, we propose P-MinCq, an extension of MinCq that can incorporate such knowledge in the form of a constraint over the distribution of the weights, along with general proofs of convergence that stand in the sample compression setting for data-dependent voters. The approach is applied to a vote of k-NN classifiers with a specific modeling of the voters' performance. P-MinCq significantly outperforms the classic k-NN classifier, a symmetric NN and MinCq using the same voters. We show that it is also competitive with LMNN, a popular metric learning algorithm, and that combining both approaches further reduces the error.
AU - Bellet, Aurélien
AU - Habrard, Amaury
AU - Morvant, Emilie
AU - Sebban, Marc
ID - 2180
IS - 1-2
JF - Machine Learning
TI - Learning a priori constrained weighted majority votes
VL - 97
ER -
TY - JOUR
AB - Given topological spaces X,Y, a fundamental problem of algebraic topology is understanding the structure of all continuous maps X→ Y. We consider a computational version, where X,Y are given as finite simplicial complexes, and the goal is to compute [X,Y], that is, all homotopy classes of suchmaps.We solve this problem in the stable range, where for some d ≥ 2, we have dim X ≤ 2d-2 and Y is (d-1)-connected; in particular, Y can be the d-dimensional sphere Sd. The algorithm combines classical tools and ideas from homotopy theory (obstruction theory, Postnikov systems, and simplicial sets) with algorithmic tools from effective algebraic topology (locally effective simplicial sets and objects with effective homology). In contrast, [X,Y] is known to be uncomputable for general X,Y, since for X = S1 it includes a well known undecidable problem: testing triviality of the fundamental group of Y. In follow-up papers, the algorithm is shown to run in polynomial time for d fixed, and extended to other problems, such as the extension problem, where we are given a subspace A ⊂ X and a map A→ Y and ask whether it extends to a map X → Y, or computing the Z2-index-everything in the stable range. Outside the stable range, the extension problem is undecidable.
AU - Čadek, Martin
AU - Krcál, Marek
AU - Matoušek, Jiří
AU - Sergeraert, Francis
AU - Vokřínek, Lukáš
AU - Wagner, Uli
ID - 2184
IS - 3
JF - Journal of the ACM
TI - Computing all maps into a sphere
VL - 61
ER -
TY - JOUR
AB - We describe a simple adaptive network of coupled chaotic maps. The network reaches a stationary state (frozen topology) for all values of the coupling parameter, although the dynamics of the maps at the nodes of the network can be nontrivial. The structure of the network shows interesting hierarchical properties and in certain parameter regions the dynamics is polysynchronous: Nodes can be divided in differently synchronized classes but, contrary to cluster synchronization, nodes in the same class need not be connected to each other. These complicated synchrony patterns have been conjectured to play roles in systems biology and circuits. The adaptive system we study describes ways whereby this behavior can evolve from undifferentiated nodes.
AU - Botella Soler, Vicente
AU - Glendinning, Paul
ID - 2183
IS - 6
JF - Physical Review E Statistical Nonlinear and Soft Matter Physics
TI - Hierarchy and polysynchrony in an adaptive network
VL - 89
ER -
TY - JOUR
AB - We prove the existence of scattering states for the defocusing cubic Gross-Pitaevskii (GP) hierarchy in ℝ3. Moreover, we show that an exponential energy growth condition commonly used in the well-posedness theory of the GP hierarchy is, in a specific sense, necessary. In fact, we prove that without the latter, there exist initial data for the focusing cubic GP hierarchy for which instantaneous blowup occurs.
AU - Chen, Thomas
AU - Hainzl, Christian
AU - Pavlović, Nataša
AU - Seiringer, Robert
ID - 2186
IS - 7
JF - Letters in Mathematical Physics
TI - On the well-posedness and scattering for the Gross-Pitaevskii hierarchy via quantum de Finetti
VL - 104
ER -
TY - JOUR
AB - Systems should not only be correct but also robust in the sense that they behave reasonably in unexpected situations. This article addresses synthesis of robust reactive systems from temporal specifications. Existing methods allow arbitrary behavior if assumptions in the specification are violated. To overcome this, we define two robustness notions, combine them, and show how to enforce them in synthesis. The first notion applies to safety properties: If safety assumptions are violated temporarily, we require that the system recovers to normal operation with as few errors as possible. The second notion requires that, if liveness assumptions are violated, as many guarantees as possible should be fulfilled nevertheless. We present a synthesis procedure achieving this for the important class of GR(1) specifications, and establish complexity bounds. We also present an implementation of a special case of robustness, and show experimental results.
AU - Bloem, Roderick
AU - Chatterjee, Krishnendu
AU - Greimel, Karin
AU - Henzinger, Thomas A
AU - Hofferek, Georg
AU - Jobstmann, Barbara
AU - Könighofer, Bettina
AU - Könighofer, Robert
ID - 2187
IS - 3-4
JF - Acta Informatica
TI - Synthesizing robust systems
VL - 51
ER -
TY - JOUR
AB - Although plant and animal cells use a similar core mechanism to deliver proteins to the plasma membrane, their different lifestyle, body organization and specific cell structures resulted in the acquisition of regulatory mechanisms that vary in the two kingdoms. In particular, cell polarity regulators do not seem to be conserved, because genes encoding key components are absent in plant genomes. In plants, the broad knowledge on polarity derives from the study of auxin transporters, the PIN-FORMED proteins, in the model plant Arabidopsis thaliana. In animals, much information is provided from the study of polarity in epithelial cells that exhibit basolateral and luminal apical polarities, separated by tight junctions. In this review, we summarize the similarities and differences of the polarization mechanisms between plants and animals and survey the main genetic approaches that have been used to characterize new genes involved in polarity establishment in plants, including the frequently used forward and reverse genetics screens as well as a novel chemical genetics approach that is expected to overcome the limitation of classical genetics methods.
AU - Kania, Urszula
AU - Fendrych, Matyas
AU - Friml, Jiřĺ
ID - 2188
IS - APRIL
JF - Open Biology
TI - Polar delivery in plants; commonalities and differences to animal epithelial cells
VL - 4
ER -
TY - CONF
AB - En apprentissage automatique, nous parlons d'adaptation de domaine lorsque les données de test (cibles) et d'apprentissage (sources) sont générées selon différentes distributions. Nous devons donc développer des algorithmes de classification capables de s'adapter à une nouvelle distribution, pour laquelle aucune information sur les étiquettes n'est disponible. Nous attaquons cette problématique sous l'angle de l'approche PAC-Bayésienne qui se focalise sur l'apprentissage de modèles définis comme des votes de majorité sur un ensemble de fonctions. Dans ce contexte, nous introduisons PV-MinCq une version adaptative de l'algorithme (non adaptatif) MinCq. PV-MinCq suit le principe suivant. Nous transférons les étiquettes sources aux points cibles proches pour ensuite appliquer MinCq sur l'échantillon cible ``auto-étiqueté'' (justifié par une borne théorique). Plus précisément, nous définissons un auto-étiquetage non itératif qui se focalise dans les régions où les distributions marginales source et cible sont les plus similaires. Dans un second temps, nous étudions l'influence de notre auto-étiquetage pour en déduire une procédure de validation des hyperparamètres. Finalement, notre approche montre des résultats empiriques prometteurs.
AU - Morvant, Emilie
ID - 2189
TI - Adaptation de domaine de vote de majorité par auto-étiquetage non itératif
VL - 1
ER -
TY - CONF
AB - We present a new algorithm to construct a (generalized) deterministic Rabin automaton for an LTL formula φ. The automaton is the product of a master automaton and an array of slave automata, one for each G-subformula of φ. The slave automaton for G ψ is in charge of recognizing whether FG ψ holds. As opposed to standard determinization procedures, the states of all our automata have a clear logical structure, which allows for various optimizations. Our construction subsumes former algorithms for fragments of LTL. Experimental results show improvement in the sizes of the resulting automata compared to existing methods.
AU - Esparza, Javier
AU - Kretinsky, Jan
ID - 2190
TI - From LTL to deterministic automata: A safraless compositional approach
VL - 8559
ER -
TY - JOUR
AB - A hallmark of immune cell trafficking is directional guidance via gradients of soluble or surface bound chemokines. Vascular endothelial cells produce, transport and deposit either their own chemokines or chemokines produced by the underlying stroma. Endothelial heparan sulfate (HS) was suggested to be a critical scaffold for these chemokine pools, but it is unclear how steep chemokine gradients are sustained between the lumenal and ablumenal aspects of blood vessels. Addressing this question by semi-quantitative immunostaining of HS moieties around blood vessels with a pan anti-HS IgM mAb, we found a striking HS enrichment in the basal lamina of resting and inflamed post capillary skin venules, as well as in high endothelial venules (HEVs) of lymph nodes. Staining of skin vessels with a glycocalyx probe further suggested that their lumenal glycocalyx contains much lower HS density than their basolateral extracellular matrix (ECM). This polarized HS pattern was observed also in isolated resting and inflamed microvascular dermal cells. Notably, progressive skin inflammation resulted in massive ECM deposition and in further HS enrichment around skin post capillary venules and their associated pericytes. Inflammation-dependent HS enrichment was not compromised in mice deficient in the main HS degrading enzyme, heparanase. Our results suggest that the blood vasculature patterns steep gradients of HS scaffolds between their lumenal and basolateral endothelial aspects, and that inflammatory processes can further enrich the HS content nearby inflamed vessels. We propose that chemokine gradients between the lumenal and ablumenal sides of vessels could be favored by these sharp HS scaffold gradients.
AU - Stoler Barak, Liat
AU - Moussion, Christine
AU - Shezen, Elias
AU - Hatzav, Miki
AU - Sixt, Michael K
AU - Alon, Ronen
ID - 2214
IS - 1
JF - PLoS One
TI - Blood vessels pattern heparan sulfate gradients between their apical and basolateral aspects
VL - 9
ER -
TY - JOUR
AB - Homologous recombination is crucial for genome stability and for genetic exchange. Although our knowledge of the principle steps in recombination and its machinery is well advanced, homology search, the critical step of exploring the genome for homologous sequences to enable recombination, has remained mostly enigmatic. However, recent methodological advances have provided considerable new insights into this fundamental step in recombination that can be integrated into a mechanistic model. These advances emphasize the importance of genomic proximity and nuclear organization for homology search and the critical role of homology search mediators in this process. They also aid our understanding of how homology search might lead to unwanted and potentially disease-promoting recombination events.
AU - Renkawitz, Jörg
AU - Lademann, Claudio
AU - Jentsch, Stefan
ID - 2215
IS - 6
JF - Nature Reviews Molecular Cell Biology
TI - Mechanisms and principles of homology search during recombination
VL - 15
ER -
TY - JOUR
AB - Correct positioning of membrane proteins is an essential process in eukaryotic organisms. The plant hormone auxin is distributed through intercellular transport and triggers various cellular responses. Auxin transporters of the PIN-FORMED (PIN) family localize asymmetrically at the plasma membrane (PM) and mediate the directional transport of auxin between cells. A fungal toxin, brefeldin A (BFA), inhibits a subset of guanine nucleotide exchange factors for ADP-ribosylation factor small GTPases (ARF GEFs) including GNOM, which plays a major role in localization of PIN1 predominantly to the basal side of the PM. The Arabidopsis genome encodes 19 ARF-related putative GTPases. However, ARF components involved in PIN1 localization have been genetically poorly defined. Using a fluorescence imaging-based forward genetic approach, we identified an Arabidopsis mutant, bfa-visualized exocytic trafficking defective1 (bex1), in which PM localization of PIN1-green fluorescent protein (GFP) as well as development is hypersensitive to BFA. We found that in bex1 a member of the ARF1 gene family, ARF1A1C, was mutated. ARF1A1C localizes to the trans-Golgi network/early endosome and Golgi apparatus, acts synergistically to BEN1/MIN7 ARF GEF and is important for PIN recycling to the PM. Consistent with the developmental importance of PIN proteins, functional interference with ARF1 resulted in an impaired auxin response gradient and various developmental defects including embryonic patterning defects and growth arrest. Our results show that ARF1A1C is essential for recycling of PIN auxin transporters and for various auxin-dependent developmental processes.
AU - Tanaka, Hirokazu
AU - Nodzyński, Tomasz
AU - Kitakura, Saeko
AU - Feraru, Mugurel
AU - Sasabe, Michiko
AU - Ishikawa, Tomomi
AU - Kleine Vehn, Jürgen
AU - Kakimoto, Tatsuo
AU - Friml, Jirí
ID - 2223
IS - 4
JF - Plant and Cell Physiology
SN - 00320781
TI - BEX1/ARF1A1C is required for BFA-sensitive recycling of PIN auxin transporters and auxin-mediated development in arabidopsis
VL - 55
ER -
TY - JOUR
AB - We consider sample covariance matrices of the form X∗X, where X is an M×N matrix with independent random entries. We prove the isotropic local Marchenko-Pastur law, i.e. we prove that the resolvent (X∗X−z)−1 converges to a multiple of the identity in the sense of quadratic forms. More precisely, we establish sharp high-probability bounds on the quantity ⟨v,(X∗X−z)−1w⟩−⟨v,w⟩m(z), where m is the Stieltjes transform of the Marchenko-Pastur law and v,w∈CN. We require the logarithms of the dimensions M and N to be comparable. Our result holds down to scales Iz≥N−1+ε and throughout the entire spectrum away from 0. We also prove analogous results for generalized Wigner matrices.
AU - Bloemendal, Alex
AU - Erdös, László
AU - Knowles, Antti
AU - Yau, Horng
AU - Yin, Jun
ID - 2225
JF - Electronic Journal of Probability
SN - 10836489
TI - Isotropic local laws for sample covariance and generalized Wigner matrices
VL - 19
ER -
TY - JOUR
AB - Leaf venation develops complex patterns in angiosperms, but the mechanism underlying this process is largely unknown. To elucidate the molecular mechanisms governing vein pattern formation, we previously isolated vascular network defective (van) mutants that displayed venation discontinuities. Here, we report the phenotypic analysis of van4 mutants, and we identify and characterize the VAN4 gene. Detailed phenotypic analysis shows that van4 mutants are defective in procambium cell differentiation and subsequent vascular cell differentiation. Reduced shoot and root cell growth is observed in van4 mutants, suggesting that VAN4 function is important for cell growth and the establishment of venation continuity. Consistent with these phenotypes, the VAN4 gene is strongly expressed in vascular and meristematic cells. VAN4 encodes a putative TRS120, which is a known guanine nucleotide exchange factor (GEF) for Rab GTPase involved in regulating vesicle transport, and a known tethering factor that determines the specificity of membrane fusion. VAN4 protein localizes at the trans-Golgi network/early endosome (TGN/EE). Aberrant recycling of the auxin efflux carrier PIN proteins is observed in van4 mutants. These results suggest that VAN4-mediated exocytosis at the TGN plays important roles in plant vascular development and cell growth in shoot and root. Our identification of VAN4 as a putative TRS120 shows that Rab GTPases are crucial (in addition to ARF GTPases) for continuous vascular development, and provides further evidence for the importance of vesicle transport in leaf vascular formation.
AU - Naramoto, Satoshi
AU - Nodzyński, Tomasz
AU - Dainobu, Tomoko
AU - Takatsuka, Hirotomo
AU - Okada, Teruyo
AU - Friml, Jirí
AU - Fukuda, Hiroo
ID - 2222
IS - 4
JF - Plant and Cell Physiology
SN - 00320781
TI - VAN4 encodes a putative TRS120 that is required for normal cell growth and vein development in arabidopsis
VL - 55
ER -
TY - JOUR
AB - This work investigates the transition between different traveling helical waves (spirals, SPIs) in the setup of differentially independent rotating cylinders. We use direct numerical simulations to consider an infinite long and periodic Taylor-Couette apparatus with fixed axial periodicity length. We find so-called mixed-cross-spirals (MCSs), that can be seen as nonlinear superpositions of SPIs, to establish stable footbridges connecting SPI states. While bridging the bifurcation branches of SPIs, the corresponding contributions within the MCS vary continuously with the control parameters. Here discussed MCSs presenting footbridge solutions start and end in different SPI branches. Therefore they differ significantly from the already known MCSs that present bypass solutions (Altmeyer and Hoffmann 2010 New J. Phys. 12 113035). The latter start and end in the same SPI branch, while they always bifurcate out of those SPI branches with the larger mode amplitude. Meanwhile, these only appear within the coexisting region of both SPIs. In contrast, the footbridge solutions can also bifurcate out of the minor SPI contribution. We also find they exist in regions where only one of the SPIs contributions exists. In addition, MCS as footbridge solution can appear either stable or unstable. The latter detected transient solutions offer similar spatio-temporal characteristics to the flow establishing stable footbridges. Such transition processes are interesting for pattern-forming systems in general because they accomplish transitions between traveling waves of different azimuthal wave numbers and have not been described in the literature yet.
AU - Altmeyer, Sebastian
ID - 2224
IS - 2
JF - Fluid Dynamics Research
SN - 01695983
TI - On secondary instabilities generating footbridges between spiral vortex flow
VL - 46
ER -
TY - CONF
AB - Recently, Döttling et al. (ASIACRYPT 2012) proposed the first chosen-ciphertext (IND-CCA) secure public-key encryption scheme from the learning parity with noise (LPN) assumption. In this work we give an alternative scheme which is conceptually simpler and more efficient. At the core of our construction is a trapdoor technique originally proposed for lattices by Micciancio and Peikert (EUROCRYPT 2012), which we adapt to the LPN setting. The main technical tool is a new double-trapdoor mechanism, together with a trapdoor switching lemma based on a computational variant of the leftover hash lemma.
AU - Kiltz, Eike
AU - Masny, Daniel
AU - Pietrzak, Krzysztof Z
ID - 2219
SN - 978-364254630-3
TI - Simple chosen-ciphertext security from low noise LPN
VL - 8383
ER -
TY - JOUR
AB - In this issue of Chemistry & Biology, Cokol and colleagues report a systematic study of drug interactions between antifungal compounds. Suppressive drug interactions occur more frequently than previously realized and come in different flavors with interesting implications.
AU - De Vos, Marjon
AU - Bollenbach, Mark Tobias
ID - 2220
IS - 4
JF - Chemistry and Biology
SN - 10745521
TI - Suppressive drug interactions between antifungals
VL - 21
ER -
TY - JOUR
AB - A discounted-sum automaton (NDA) is a nondeterministic finite automaton with edge weights, valuing a run by the discounted sum of visited edge weights. More precisely, the weight in the i-th position of the run is divided by λi, where the discount factor λ is a fixed rational number greater than 1. The value of a word is the minimal value of the automaton runs on it. Discounted summation is a common and useful measuring scheme, especially for infinite sequences, reflecting the assumption that earlier weights are more important than later weights. Unfortunately, determinization of NDAs, which is often essential in formal verification, is, in general, not possible. We provide positive news, showing that every NDA with an integral discount factor is determinizable. We complete the picture by proving that the integers characterize exactly the discount factors that guarantee determinizability: for every nonintegral rational discount factor λ, there is a nondeterminizable λ-NDA. We also prove that the class of NDAs with integral discount factors enjoys closure under the algebraic operations min, max, addition, and subtraction, which is not the case for general NDAs nor for deterministic NDAs. For general NDAs, we look into approximate determinization, which is always possible as the influence of a word's suffix decays. We show that the naive approach, of unfolding the automaton computations up to a sufficient level, is doubly exponential in the discount factor. We provide an alternative construction for approximate determinization, which is singly exponential in the discount factor, in the precision, and in the number of states. We also prove matching lower bounds, showing that the exponential dependency on each of these three parameters cannot be avoided. All our results hold equally for automata over finite words and for automata over infinite words.
AU - Boker, Udi
AU - Henzinger, Thomas A
ID - 2233
IS - 1
JF - Logical Methods in Computer Science
SN - 18605974
TI - Exact and approximate determinization of discounted-sum automata
VL - 10
ER -
TY - JOUR
AB - Intracellular electrophysiological recordings provide crucial insights into elementary neuronal signals such as action potentials and synaptic currents. Analyzing and interpreting these signals is essential for a quantitative understanding of neuronal information processing, and requires both fast data visualization and ready access to complex analysis routines. To achieve this goal, we have developed Stimfit, a free software package for cellular neurophysiology with a Python scripting interface and a built-in Python shell. The program supports most standard file formats for cellular neurophysiology and other biomedical signals through the Biosig library. To quantify and interpret the activity of single neurons and communication between neurons, the program includes algorithms to characterize the kinetics of presynaptic action potentials and postsynaptic currents, estimate latencies between pre- and postsynaptic events, and detect spontaneously occurring events. We validate and benchmark these algorithms, give estimation errors, and provide sample use cases, showing that Stimfit represents an efficient, accessible and extensible way to accurately analyze and interpret neuronal signals.
AU - Guzmán, José
AU - Schlögl, Alois
AU - Schmidt Hieber, Christoph
ID - 2230
IS - FEB
JF - Frontiers in Neuroinformatics
SN - 16625196
TI - Stimfit: Quantifying electrophysiological data with Python
VL - 8
ER -
TY - JOUR
AB - Fast-spiking, parvalbumin-expressing GABAergic interneurons, a large proportion of which are basket cells (BCs), have a key role in feedforward and feedback inhibition, gamma oscillations and complex information processing. For these functions, fast propagation of action potentials (APs) from the soma to the presynaptic terminals is important. However, the functional properties of interneuron axons remain elusive. We examined interneuron axons by confocally targeted subcellular patch-clamp recording in rat hippocampal slices. APs were initiated in the proximal axon ∼20 μm from the soma and propagated to the distal axon with high reliability and speed. Subcellular mapping revealed a stepwise increase of Na^+ conductance density from the soma to the proximal axon, followed by a further gradual increase in the distal axon. Active cable modeling and experiments with partial channel block revealed that low axonal Na^+ conductance density was sufficient for reliability, but high Na^+ density was necessary for both speed of propagation and fast-spiking AP phenotype. Our results suggest that a supercritical density of Na^+ channels compensates for the morphological properties of interneuron axons (small segmental diameter, extensive branching and high bouton density), ensuring fast AP propagation and high-frequency repetitive firing.
AU - Hu, Hua
AU - Jonas, Peter M
ID - 2228
IS - 5
JF - Nature Neuroscience
SN - 10976256
TI - A supercritical density of Na^+ channels ensures fast signaling in GABAergic interneuron axons
VL - 17
ER -
TY - JOUR
AB - The distance between Ca^2+ channels and release sensors determines the speed and efficacy of synaptic transmission. Tight "nanodomain" channel-sensor coupling initiates transmitter release at synapses in the mature brain, whereas loose "microdomain" coupling appears restricted to early developmental stages. To probe the coupling configuration at a plastic synapse in the mature central nervous system, we performed paired recordings between mossy fiber terminals and CA3 pyramidal neurons in rat hippocampus. Millimolar concentrations of both the fast Ca^2+ chelator BAPTA [1,2-bis(2-aminophenoxy)ethane- N,N, N′,N′-tetraacetic acid] and the slow chelator EGTA efficiently suppressed transmitter release, indicating loose coupling between Ca^2+ channels and release sensors. Loose coupling enabled the control of initial release probability by fast endogenous Ca^2+ buffers and the generation of facilitation by buffer saturation. Thus, loose coupling provides the molecular framework for presynaptic plasticity.
AU - Vyleta, Nicholas
AU - Jonas, Peter M
ID - 2229
IS - 6171
JF - Science
SN - 00368075
TI - Loose coupling between Ca^2+ channels and release sensors at a plastic hippocampal synapse
VL - 343
ER -
TY - JOUR
AB - The purpose of this contribution is to summarize and discuss recent advances regarding the onset of turbulence in shear flows. The absence of a clear-cut instability mechanism, the spatio-temporal intermittent character and extremely long lived transients are some of the major difficulties encountered in these flows and have hindered progress towards understanding the transition process. We will show for the case of pipe flow that concepts from nonlinear dynamics and statistical physics can help to explain the onset of turbulence. In particular, the turbulent structures (puffs) observed close to onset are spatially localized chaotic transients and their lifetimes increase super-exponentially with Reynolds number. At the same time fluctuations of individual turbulent puffs can (although very rarely) lead to the nucleation of new puffs. The competition between these two stochastic processes gives rise to a non-equilibrium phase transition where turbulence changes from a super-transient to a sustained state.
AU - Song, Baofang
AU - Hof, Björn
ID - 2232
IS - 2
JF - Journal of Statistical Mechanics Theory and Experiment
SN - 17425468
TI - Deterministic and stochastic aspects of the transition to turbulence
VL - 2014
ER -
TY - JOUR
AB - Based on the measurements of noise in gene expression performed during the past decade, it has become customary to think of gene regulation in terms of a two-state model, where the promoter of a gene can stochastically switch between an ON and an OFF state. As experiments are becoming increasingly precise and the deviations from the two-state model start to be observable, we ask about the experimental signatures of complex multistate promoters, as well as the functional consequences of this additional complexity. In detail, we i), extend the calculations for noise in gene expression to promoters described by state transition diagrams with multiple states, ii), systematically compute the experimentally accessible noise characteristics for these complex promoters, and iii), use information theory to evaluate the channel capacities of complex promoter architectures and compare them with the baseline provided by the two-state model. We find that adding internal states to the promoter generically decreases channel capacity, except in certain cases, three of which (cooperativity, dual-role regulation, promoter cycling) we analyze in detail.
AU - Rieckh, Georg
AU - Tkacik, Gasper
ID - 2231
IS - 5
JF - Biophysical Journal
SN - 00063495
TI - Noise and information transmission in promoters with multiple internal states
VL - 106
ER -
TY - JOUR
AB - Coriolis force effects on shear flows are important in geophysical and astrophysical contexts. We report a study on the linear stability and the transient energy growth of the plane Couette flow with system rotation perpendicular to the shear direction. External rotation causes linear instability. At small rotation rates, the onset of linear instability scales inversely with the rotation rate and the optimal transient growth in the linearly stable region is slightly enhanced ∼Re2. The corresponding optimal initial perturbations are characterized by roll structures inclined in the streamwise direction and are twisted under external rotation. At large rotation rates, the transient growth is significantly inhibited and hence linear stability analysis is a reliable indicator for instability.
AU - Shi, Liang
AU - Hof, Björn
AU - Tilgner, Andreas
ID - 2226
IS - 1
JF - Physical Review E Statistical Nonlinear and Soft Matter Physics
SN - 15393755
TI - Transient growth of Ekman-Couette flow
VL - 89
ER -
TY - JOUR
AB - The Balkan Peninsula, characterized by high rates of endemism, is recognised as one of the most diverse and species-rich areas of Europe. However, little is known about the origin of Balkan endemics. The present study addresses the phylogenetic position of the Balkan endemic Ranunculus wettsteinii, as well as its taxonomic status and relationship with the widespread R. parnassiifolius, based on nuclear DNA (internal transcribed spacer, ITS) and plastid regions (rpl32-trnL, rps16-trnQ, trnK-matK and ycf6-psbM). Maximum parsimony and Bayesian inference analyses revealed a well-supported clade formed by accessions of R. wettsteinii. Furthermore, our phylogenetic and network analyses supported previous hypotheses of a likely allopolyploid origin for R. wettsteinii between R. montenegrinus and R. parnassiifolius, with the latter as the maternal parent.
AU - Cires Rodriguez, Eduardo
AU - Baltisberger, Matthias
AU - Cuesta, Candela
AU - Vargas, Pablo
AU - Prieto, José
ID - 2227
IS - 1
JF - Organisms Diversity and Evolution
SN - 14396092
TI - Allopolyploid origin of the Balkan endemic Ranunculus wettsteinii (Ranunculaceae) inferred from nuclear and plastid DNA sequences
VL - 14
ER -
TY - JOUR
AB - We study Markov decision processes (MDPs) with multiple limit-average (or mean-payoff) functions. We consider two different objectives, namely, expectation and satisfaction objectives. Given an MDP with κ limit-average functions, in the expectation objective the goal is to maximize the expected limit-average value, and in the satisfaction objective the goal is to maximize the probability of runs such that the limit-average value stays above a given vector. We show that under the expectation objective, in contrast to the case of one limit-average function, both randomization and memory are necessary for strategies even for ε-approximation, and that finite-memory randomized strategies are sufficient for achieving Pareto optimal values. Under the satisfaction objective, in contrast to the case of one limit-average function, infinite memory is necessary for strategies achieving a specific value (i.e. randomized finite-memory strategies are not sufficient), whereas memoryless randomized strategies are sufficient for ε-approximation, for all ε > 0. We further prove that the decision problems for both expectation and satisfaction objectives can be solved in polynomial time and the trade-off curve (Pareto curve) can be ε-approximated in time polynomial in the size of the MDP and 1/ε, and exponential in the number of limit-average functions, for all ε > 0. Our analysis also reveals flaws in previous work for MDPs with multiple mean-payoff functions under the expectation objective, corrects the flaws, and allows us to obtain improved results.
AU - Brázdil, Tomáš
AU - Brožek, Václav
AU - Chatterjee, Krishnendu
AU - Forejt, Vojtěch
AU - Kučera, Antonín
ID - 2234
IS - 1
JF - Logical Methods in Computer Science
SN - 18605974
TI - Markov decision processes with multiple long-run average objectives
VL - 10
ER -
TY - CONF
AB - Consider a joint distribution (X,A) on a set. We show that for any family of distinguishers, there exists a simulator such that 1 no function in can distinguish (X,A) from (X,h(X)) with advantage ε, 2 h is only O(2 3ℓ ε -2) times less efficient than the functions in. For the most interesting settings of the parameters (in particular, the cryptographic case where X has superlogarithmic min-entropy, ε > 0 is negligible and consists of circuits of polynomial size), we can make the simulator h deterministic. As an illustrative application of our theorem, we give a new security proof for the leakage-resilient stream-cipher from Eurocrypt'09. Our proof is simpler and quantitatively much better than the original proof using the dense model theorem, giving meaningful security guarantees if instantiated with a standard blockcipher like AES. Subsequent to this work, Chung, Lui and Pass gave an interactive variant of our main theorem, and used it to investigate weak notions of Zero-Knowledge. Vadhan and Zheng give a more constructive version of our theorem using their new uniform min-max theorem.
AU - Jetchev, Dimitar
AU - Pietrzak, Krzysztof Z
ED - Lindell, Yehuda
ID - 2236
SN - 978-364254241-1
TI - How to fake auxiliary input
VL - 8349
ER -
TY - JOUR
AB - Clathrin-mediated endocytosis is the major mechanism for eukaryotic plasma membrane-based proteome turn-over. In plants, clathrin-mediated endocytosis is essential for physiology and development, but the identification and organization of the machinery operating this process remains largely obscure. Here, we identified an eight-core-component protein complex, the TPLATE complex, essential for plant growth via its role as major adaptor module for clathrin-mediated endocytosis. This complex consists of evolutionarily unique proteins that associate closely with core endocytic elements. The TPLATE complex is recruited as dynamic foci at the plasma membrane preceding recruitment of adaptor protein complex 2, clathrin, and dynamin-related proteins. Reduced function of different complex components severely impaired internalization of assorted endocytic cargoes, demonstrating its pivotal role in clathrin-mediated endocytosis. Taken together, the TPLATE complex is an early endocytic module representing a unique evolutionary plant adaptation of the canonical eukaryotic pathway for clathrin-mediated endocytosis.
AU - Gadeyne, Astrid
AU - Sánchez Rodríguez, Clara
AU - Vanneste, Steffen
AU - Di Rubbo, Simone
AU - Zauber, Henrik
AU - Vanneste, Kevin
AU - Van Leene, Jelle
AU - De Winne, Nancy
AU - Eeckhout, Dominique
AU - Persiau, Geert
AU - Van De Slijke, Eveline
AU - Cannoot, Bernard
AU - Vercruysse, Leen
AU - Mayers, Jonathan
AU - Adamowski, Maciek
AU - Kania, Urszula
AU - Ehrlich, Matthias
AU - Schweighofer, Alois
AU - Ketelaar, Tijs
AU - Maere, Steven
AU - Bednarek, Sebastian
AU - Friml, Jirí
AU - Gevaert, Kris
AU - Witters, Erwin
AU - Russinova, Eugenia
AU - Persson, Staffan
AU - De Jaeger, Geert
AU - Van Damme, Daniël
ID - 2240
IS - 4
JF - Cell
SN - 00928674
TI - The TPLATE adaptor complex drives clathrin-mediated endocytosis in plants
VL - 156
ER -
TY - CONF
AB - The analysis of the energy consumption of software is an important goal for quantitative formal methods. Current methods, using weighted transition systems or energy games, model the energy source as an ideal resource whose status is characterized by one number, namely the amount of remaining energy. Real batteries, however, exhibit behaviors that can deviate substantially from an ideal energy resource. Based on a discretization of a standard continuous battery model, we introduce battery transition systems. In this model, a battery is viewed as consisting of two parts-the available-charge tank and the bound-charge tank. Any charge or discharge is applied to the available-charge tank. Over time, the energy from each tank diffuses to the other tank. Battery transition systems are infinite state systems that, being not well-structured, fall into no decidable class that is known to us. Nonetheless, we are able to prove that the !-regular modelchecking problem is decidable for battery transition systems. We also present a case study on the verification of control programs for energy-constrained semi-autonomous robots.
AU - Boker, Udi
AU - Henzinger, Thomas A
AU - Radhakrishna, Arjun
ID - 2239
IS - 1
SN - 978-145032544-8
TI - Battery transition systems
VL - 49
ER -
TY - JOUR
AB - Emerging infectious diseases (EIDs) pose a risk to human welfare, both directly and indirectly, by affecting managed livestock and wildlife that provide valuable resources and ecosystem services, such as the pollination of crops. Honeybees (Apis mellifera), the prevailing managed insect crop pollinator, suffer from a range of emerging and exotic high-impact pathogens, and population maintenance requires active management by beekeepers to control them. Wild pollinators such as bumblebees (Bombus spp.) are in global decline, one cause of which may be pathogen spillover from managed pollinators like honeybees or commercial colonies of bumblebees. Here we use a combination of infection experiments and landscape-scale field data to show that honeybee EIDs are indeed widespread infectious agents within the pollinator assemblage. The prevalence of deformed wing virus (DWV) and the exotic parasite Nosema ceranae in honeybees and bumblebees is linked; as honeybees have higher DWV prevalence, and sympatric bumblebees and honeybees are infected by the same DWV strains, Apis is the likely source of at least one major EID in wild pollinators. Lessons learned from vertebrates highlight the need for increased pathogen control in managed bee species to maintain wild pollinators, as declines in native pollinators may be caused by interspecies pathogen transmission originating from managed pollinators.
AU - Fürst, Matthias
AU - Mcmahon, Dino
AU - Osborne, Juliet
AU - Paxton, Robert
AU - Brown, Mark
ID - 2235
IS - 7488
JF - Nature
SN - 00280836
TI - Disease associations between honeybees and bumblebees as a threat to wild pollinators
VL - 506
ER -
TY - JOUR
AB - The brain demands high-energy supply and obstruction of blood flow causes rapid deterioration of the healthiness of brain cells. Two major events occur upon ischemia: acidosis and liberation of excess glutamate, which leads to excitotoxicity. However, cellular source of glutamate and its release mechanism upon ischemia remained unknown. Here we show a causal relationship between glial acidosis and neuronal excitotoxicity. As the major cation that flows through channelrhodopsin-2 (ChR2) is proton, this could be regarded as an optogenetic tool for instant intracellular acidification. Optical activation of ChR2 expressed in glial cells led to glial acidification and to release of glutamate. On the other hand, glial alkalization via optogenetic activation of a proton pump, archaerhodopsin (ArchT), led to cessation of glutamate release and to the relief of ischemic brain damage in vivo. Our results suggest that controlling glial pH may be an effective therapeutic strategy for intervention of ischemic brain damage.
AU - Beppu, Kaoru
AU - Sasaki, Takuya
AU - Tanaka, Kenji
AU - Yamanaka, Akihiro
AU - Fukazawa, Yugo
AU - Shigemoto, Ryuichi
AU - Matsui, Ko
ID - 2241
IS - 2
JF - Neuron
SN - 08966273
TI - Optogenetic countering of glial acidosis suppresses glial glutamate release and ischemic brain damage
VL - 81
ER -
TY - CHAP
AB - Exogenous application of biologically important molecules for plant growth promotion and/or regulation is very common both in plant research and horticulture. Plant hormones such as auxins and cytokinins are classes of compounds which are often applied exogenously. Nevertheless, plants possess a well-established machinery to regulate the active pool of exogenously applied compounds by converting them to metabolites and conjugates. Consequently, it is often very useful to know the in vivo status of applied compounds to connect them with some of the regulatory events in plant developmental processes. The in vivo status of applied compounds can be measured by incubating plants with radiolabeled compounds, followed by extraction, purification, and HPLC metabolic profiling of plant extracts. Recently we have used this method to characterize the intracellularly localized PIN protein, PIN5. Here we explain the method in detail, with a focus on general application.
AU - Simon, Sibu
AU - Skůpa, Petr
AU - Dobrev, Petre
AU - Petrášek, Jan
AU - Zažímalová, Eva
AU - Friml, Jirí
ED - Hicks, Glenn
ED - Robert, Stéphanie
ID - 2245
SN - 10643745
T2 - Plant Chemical Genomics
TI - Analyzing the in vivo status of exogenously applied auxins: A HPLC-based method to characterize the intracellularly localized auxin transporters
VL - 1056
ER -