TY - JOUR
AB - Advances in multi-unit recordings pave the way for statistical modeling of activity patterns in large neural populations. Recent studies have shown that the summed activity of all neurons strongly shapes the population response. A separate recent finding has been that neural populations also exhibit criticality, an anomalously large dynamic range for the probabilities of different population activity patterns. Motivated by these two observations, we introduce a class of probabilistic models which takes into account the prior knowledge that the neural population could be globally coupled and close to critical. These models consist of an energy function which parametrizes interactions between small groups of neurons, and an arbitrary positive, strictly increasing, and twice differentiable function which maps the energy of a population pattern to its probability. We show that: 1) augmenting a pairwise Ising model with a nonlinearity yields an accurate description of the activity of retinal ganglion cells which outperforms previous models based on the summed activity of neurons; 2) prior knowledge that the population is critical translates to prior expectations about the shape of the nonlinearity; 3) the nonlinearity admits an interpretation in terms of a continuous latent variable globally coupling the system whose distribution we can infer from data. Our method is independent of the underlying system’s state space; hence, it can be applied to other systems such as natural scenes or amino acid sequences of proteins which are also known to exhibit criticality.
AU - Humplik, Jan
AU - Tkacik, Gasper
ID - 720
IS - 9
JF - PLoS Computational Biology
SN - 1553734X
TI - Probabilistic models for neural populations that naturally capture global coupling and criticality
VL - 13
ER -
TY - JOUR
AB - Let S be a positivity-preserving symmetric linear operator acting on bounded functions. The nonlinear equation -1/m=z+Sm with a parameter z in the complex upper half-plane ℍ has a unique solution m with values in ℍ. We show that the z-dependence of this solution can be represented as the Stieltjes transforms of a family of probability measures v on ℝ. Under suitable conditions on S, we show that v has a real analytic density apart from finitely many algebraic singularities of degree at most 3. Our motivation comes from large random matrices. The solution m determines the density of eigenvalues of two prominent matrix ensembles: (i) matrices with centered independent entries whose variances are given by S and (ii) matrices with correlated entries with a translation-invariant correlation structure. Our analysis shows that the limiting eigenvalue density has only square root singularities or cubic root cusps; no other singularities occur.
AU - Ajanki, Oskari H
AU - Krüger, Torben H
AU - Erdös, László
ID - 721
IS - 9
JF - Communications on Pure and Applied Mathematics
SN - 00103640
TI - Singularities of solutions to quadratic vector equations on the complex upper half plane
VL - 70
ER -
TY - JOUR
AB - Plants are sessile organisms rooted in one place. The soil resources that plants require are often distributed in a highly heterogeneous pattern. To aid foraging, plants have evolved roots whose growth and development are highly responsive to soil signals. As a result, 3D root architecture is shaped by myriad environmental signals to ensure resource capture is optimised and unfavourable environments are avoided. The first signals sensed by newly germinating seeds — gravity and light — direct root growth into the soil to aid seedling establishment. Heterogeneous soil resources, such as water, nitrogen and phosphate, also act as signals that shape 3D root growth to optimise uptake. Root architecture is also modified through biotic interactions that include soil fungi and neighbouring plants. This developmental plasticity results in a ‘custom-made’ 3D root system that is best adapted to forage for resources in each soil environment that a plant colonises.
AU - Morris, Emily
AU - Griffiths, Marcus
AU - Golebiowska, Agata
AU - Mairhofer, Stefan
AU - Burr Hersey, Jasmine
AU - Goh, Tatsuaki
AU - Von Wangenheim, Daniel
AU - Atkinson, Brian
AU - Sturrock, Craig
AU - Lynch, Jonathan
AU - Vissenberg, Kris
AU - Ritz, Karl
AU - Wells, Darren
AU - Mooney, Sacha
AU - Bennett, Malcolm
ID - 722
IS - 17
JF - Current Biology
SN - 09609822
TI - Shaping 3D root system architecture
VL - 27
ER -
TY - JOUR
AB - Individual computations and social interactions underlying collective behavior in groups of animals are of great ethological, behavioral, and theoretical interest. While complex individual behaviors have successfully been parsed into small dictionaries of stereotyped behavioral modes, studies of collective behavior largely ignored these findings; instead, their focus was on inferring single, mode-independent social interaction rules that reproduced macroscopic and often qualitative features of group behavior. Here, we bring these two approaches together to predict individual swimming patterns of adult zebrafish in a group. We show that fish alternate between an “active” mode, in which they are sensitive to the swimming patterns of conspecifics, and a “passive” mode, where they ignore them. Using a model that accounts for these two modes explicitly, we predict behaviors of individual fish with high accuracy, outperforming previous approaches that assumed a single continuous computation by individuals and simple metric or topological weighing of neighbors’ behavior. At the group level, switching between active and passive modes is uncorrelated among fish, but correlated directional swimming behavior still emerges. Our quantitative approach for studying complex, multi-modal individual behavior jointly with emergent group behavior is readily extensible to additional behavioral modes and their neural correlates as well as to other species.
AU - Harpaz, Roy
AU - Tkacik, Gasper
AU - Schneidman, Elad
ID - 725
IS - 38
JF - PNAS
SN - 00278424
TI - Discrete modes of social information processing predict individual behavior of fish in a group
VL - 114
ER -
TY - JOUR
AB - We investigate the stationary and dynamical behavior of an Anderson localized chain coupled to a single central bound state. Although this coupling partially dilutes the Anderson localized peaks towards nearly resonant sites, the most weight of the original peaks remains unchanged. This leads to multifractal wave functions with a frozen spectrum of fractal dimensions, which is characteristic for localized phases in models with power-law hopping. Using a perturbative approach we identify two different dynamical regimes. At weak couplings to the central site, the transport of particles and information is logarithmic in time, a feature usually attributed to many-body localization. We connect such transport to the persistence of the Poisson statistics of level spacings in parts of the spectrum. In contrast, at stronger couplings the level repulsion is established in the entire spectrum, the problem can be mapped to the Fano resonance, and the transport is ballistic.
AU - Hetterich, Daniel
AU - Serbyn, Maksym
AU - Domínguez, Fernando
AU - Pollmann, Frank
AU - Trauzettel, Björn
ID - 724
IS - 10
JF - Physical Review B
SN - 24699950
TI - Noninteracting central site model localization and logarithmic entanglement growth
VL - 96
ER -
TY - JOUR
AB - The morphogenesis of branched organs remains a subject of abiding interest. Although much is known about the underlying signaling pathways, it remains unclear how macroscopic features of branched organs, including their size, network topology, and spatial patterning, are encoded. Here, we show that, in mouse mammary gland, kidney, and human prostate, these features can be explained quantitatively within a single unifying framework of branching and annihilating random walks. Based on quantitative analyses of large-scale organ reconstructions and proliferation kinetics measurements, we propose that morphogenesis follows from the proliferative activity of equipotent tips that stochastically branch and randomly explore their environment but compete neutrally for space, becoming proliferatively inactive when in proximity with neighboring ducts. These results show that complex branched epithelial structures develop as a self-organized process, reliant upon a strikingly simple but generic rule, without recourse to a rigid and deterministic sequence of genetically programmed events.
AU - Hannezo, Edouard B
AU - Scheele, Colinda
AU - Moad, Mohammad
AU - Drogo, Nicholas
AU - Heer, Rakesh
AU - Sampogna, Rosemary
AU - Van Rheenen, Jacco
AU - Simons, Benjamin
ID - 726
IS - 1
JF - Cell
SN - 00928674
TI - A unifying theory of branching morphogenesis
VL - 171
ER -
TY - JOUR
AB - Actin filaments polymerizing against membranes power endocytosis, vesicular traffic, and cell motility. In vitro reconstitution studies suggest that the structure and the dynamics of actin networks respond to mechanical forces. We demonstrate that lamellipodial actin of migrating cells responds to mechanical load when membrane tension is modulated. In a steady state, migrating cell filaments assume the canonical dendritic geometry, defined by Arp2/3-generated 70° branch points. Increased tension triggers a dense network with a broadened range of angles, whereas decreased tension causes a shift to a sparse configuration dominated by filaments growing perpendicularly to the plasma membrane. We show that these responses emerge from the geometry of branched actin: when load per filament decreases, elongation speed increases and perpendicular filaments gradually outcompete others because they polymerize the shortest distance to the membrane, where they are protected from capping. This network-intrinsic geometrical adaptation mechanism tunes protrusive force in response to mechanical load.
AU - Mueller, Jan
AU - Szep, Gregory
AU - Nemethova, Maria
AU - De Vries, Ingrid
AU - Lieber, Arnon
AU - Winkler, Christoph
AU - Kruse, Karsten
AU - Small, John
AU - Schmeiser, Christian
AU - Keren, Kinneret
AU - Hauschild, Robert
AU - Sixt, Michael K
ID - 727
IS - 1
JF - Cell
SN - 00928674
TI - Load adaptation of lamellipodial actin networks
VL - 171
ER -
TY - JOUR
AB - During animal development, cell-fate-specific changes in gene expression can modify the material properties of a tissue and drive tissue morphogenesis. While mechanistic insights into the genetic control of tissue-shaping events are beginning to emerge, how tissue morphogenesis and mechanics can reciprocally impact cell-fate specification remains relatively unexplored. Here we review recent findings reporting how multicellular morphogenetic events and their underlying mechanical forces can feed back into gene regulatory pathways to specify cell fate. We further discuss emerging techniques that allow for the direct measurement and manipulation of mechanical signals in vivo, offering unprecedented access to study mechanotransduction during development. Examination of the mechanical control of cell fate during tissue morphogenesis will pave the way to an integrated understanding of the design principles that underlie robust tissue patterning in embryonic development.
AU - Chan, Chii
AU - Heisenberg, Carl-Philipp J
AU - Hiiragi, Takashi
ID - 728
IS - 18
JF - Current Biology
SN - 09609822
TI - Coordination of morphogenesis and cell fate specification in development
VL - 27
ER -
TY - JOUR
AB - The cellular mechanisms allowing tissues to efficiently regenerate are not fully understood. In this issue of Developmental Cell, Cao et al. (2017)) discover that during zebrafish heart regeneration, epicardial cells at the leading edge of regenerating tissue undergo endoreplication, possibly due to increased tissue tension, thereby boosting their regenerative capacity.
AU - Spiro, Zoltan P
AU - Heisenberg, Carl-Philipp J
ID - 729
IS - 6
JF - Developmental Cell
SN - 15345807
TI - Regeneration tensed up polyploidy takes the lead
VL - 42
ER -
TY - JOUR
AB - Neural responses are highly structured, with population activity restricted to a small subset of the astronomical range of possible activity patterns. Characterizing these statistical regularities is important for understanding circuit computation, but challenging in practice. Here we review recent approaches based on the maximum entropy principle used for quantifying collective behavior in neural activity. We highlight recent models that capture population-level statistics of neural data, yielding insights into the organization of the neural code and its biological substrate. Furthermore, the MaxEnt framework provides a general recipe for constructing surrogate ensembles that preserve aspects of the data, but are otherwise maximally unstructured. This idea can be used to generate a hierarchy of controls against which rigorous statistical tests are possible.
AU - Savin, Cristina
AU - Tkacik, Gasper
ID - 730
JF - Current Opinion in Neurobiology
SN - 09594388
TI - Maximum entropy models as a tool for building precise neural controls
VL - 46
ER -
TY - JOUR
AB - Genetic variations in the oxytocin receptor gene affect patients with ASD and ADHD differently.
AU - Novarino, Gaia
ID - 731
IS - 411
JF - Science Translational Medicine
SN - 19466234
TI - The science of love in ASD and ADHD
VL - 9
ER -
TY - JOUR
AB - Let A and B be two N by N deterministic Hermitian matrices and let U be an N by N Haar distributed unitary matrix. It is well known that the spectral distribution of the sum H = A + UBU∗ converges weakly to the free additive convolution of the spectral distributions of A and B, as N tends to infinity. We establish the optimal convergence rate in the bulk of the spectrum.
AU - Bao, Zhigang
AU - Erdös, László
AU - Schnelli, Kevin
ID - 733
JF - Advances in Mathematics
TI - Convergence rate for spectral distribution of addition of random matrices
VL - 319
ER -
TY - JOUR
AB - The neurotransmitter receptor subtype, number, density, and distribution relative to the location of transmitter release sites are key determinants of signal transmission. AMPA-type ionotropic glutamate receptors (AMPARs) containing GluA3 and GluA4 subunits are prominently expressed in subsets of neurons capable of firing action potentials at high frequencies, such as auditory relay neurons. The auditory nerve (AN) forms glutamatergic synapses on two types of relay neurons, bushy cells (BCs) and fusiform cells (FCs) of the cochlear nucleus. AN-BC and AN-FC synapses have distinct kinetics; thus, we investigated whether the number, density, and localization of GluA3 and GluA4 subunits in these synapses are differentially organized using quantitative freeze-fracture replica immunogold labeling. We identify a positive correlation between the number of AMPARs and the size of AN-BC and AN-FC synapses. Both types of AN synapses have similar numbers of AMPARs; however, the AN-BC have a higher density of AMPARs than AN-FC synapses, because the AN-BC synapses are smaller. A higher number and density of GluA3 subunits are observed at AN-BC synapses, whereas a higher number and density of GluA4 subunits are observed at AN-FC synapses. The intrasynaptic distribution of immunogold labeling revealed that AMPAR subunits, particularly GluA3, are concentrated at the center of the AN-BC synapses. The central distribution of AMPARs is absent in GluA3-knockout mice, and gold particles are evenly distributed along the postsynaptic density. GluA4 gold labeling was homogenously distributed along both synapse types. Thus, GluA3 and GluA4 subunits are distributed at AN synapses in a target-cell-dependent manner.
AU - Rubio, María
AU - Matsui, Ko
AU - Fukazawa, Yugo
AU - Kamasawa, Naomi
AU - Harada, Harumi
AU - Itakura, Makoto
AU - Molnár, Elek
AU - Abe, Manabu
AU - Sakimura, Kenji
AU - Shigemoto, Ryuichi
ID - 736
IS - 8
JF - Brain Structure and Function
SN - 18632653
TI - The number and distribution of AMPA receptor channels containing fast kinetic GluA3 and GluA4 subunits at auditory nerve synapses depend on the target cells
VL - 222
ER -
TY - JOUR
AB - Inflammation, which is a highly regulated host response against danger signals, may be harmful if it is excessive and deregulated. Ideally, anti-inflammatory therapy should autonomously commence as soon as possible after the onset of inflammation, should be controllable by a physician, and should not systemically block beneficial immune response in the long term. We describe a genetically encoded anti-inflammatory mammalian cell device based on a modular engineered genetic circuit comprising a sensor, an amplifier, a “thresholder” to restrict activation of a positive-feedback loop, a combination of advanced clinically used biopharmaceutical proteins, and orthogonal regulatory elements that linked modules into the functional device. This genetic circuit was autonomously activated by inflammatory signals, including endogenous cecal ligation and puncture (CLP)-induced inflammation in mice and serum from a systemic juvenile idiopathic arthritis (sIJA) patient, and could be reset externally by a chemical signal. The microencapsulated anti-inflammatory device significantly reduced the pathology in dextran sodium sulfate (DSS)-induced acute murine colitis, demonstrating a synthetic immunological approach for autonomous anti-inflammatory therapy.
AU - Smole, Anže
AU - Lainšček, Duško
AU - Bezeljak, Urban
AU - Horvat, Simon
AU - Jerala, Roman
ID - 7360
IS - 1
JF - Molecular Therapy
SN - 1525-0016
TI - A synthetic mammalian therapeutic gene circuit for sensing and suppressing inflammation
VL - 25
ER -
TY - JOUR
AB - We generalize Brazas’ topology on the fundamental group to the whole universal path space X˜ i.e., to the set of homotopy classes of all based paths. We develop basic properties of the new notion and provide a complete comparison of the obtained topology with the established topologies, in particular with the Lasso topology and the CO topology, i.e., the topology that is induced by the compact-open topology. It turns out that the new topology is the finest topology contained in the CO topology, for which the action of the fundamental group on the universal path space is a continuous group action.
AU - Virk, Ziga
AU - Zastrow, Andreas
ID - 737
JF - Topology and its Applications
SN - 01668641
TI - A new topology on the universal path space
VL - 231
ER -
TY - JOUR
AB - We study the norm approximation to the Schrödinger dynamics of N bosons in with an interaction potential of the form . Assuming that in the initial state the particles outside of the condensate form a quasi-free state with finite kinetic energy, we show that in the large N limit, the fluctuations around the condensate can be effectively described using Bogoliubov approximation for all . The range of β is expected to be optimal for this large class of initial states.
AU - Nam, Phan
AU - Napiórkowski, Marcin M
ID - 739
IS - 5
JF - Journal de Mathématiques Pures et Appliquées
SN - 00217824
TI - A note on the validity of Bogoliubov correction to mean field dynamics
VL - 108
ER -
TY - JOUR
AB - Developments in bioengineering and molecular biology have introduced a palette of genetically encoded probes for identification of specific cell populations in electron microscopy. These probes can be targeted to distinct cellular compartments, rendering them electron dense through a subsequent chemical reaction. These electron densities strongly increase the local contrast in samples prepared for electron microscopy, allowing three major advances in ultrastructural mapping of circuits: genetic identification of circuit components, targeted imaging of regions of interest and automated analysis of the tagged circuits. Together, the gains from these advances can decrease the time required for the analysis of targeted circuit motifs by over two orders of magnitude. These genetic encoded tags for electron microscopy promise to simplify the analysis of circuit motifs and become a central tool for structure‐function studies of synaptic connections in the brain. We review the current state‐of‐the‐art with an emphasis on connectomics, the quantitative analysis of neuronal structures and motifs.
AU - Shigemoto, Ryuichi
AU - Jösch, Maximilian A
ID - 740
IS - 6
JF - WIREs Developmental Biology
SN - 17597684
TI - The genetic encoded toolbox for electron microscopy and connectomics
VL - 6
ER -
TY - JOUR
AB - In evolutionary game theory interactions between individuals are often assumed obligatory. However, in many real-life situations, individuals can decide to opt out of an interaction depending on the information they have about the opponent. We consider a simple evolutionary game theoretic model to study such a scenario, where at each encounter between two individuals the type of the opponent (cooperator/defector) is known with some probability, and where each individual either accepts or opts out of the interaction. If the type of the opponent is unknown, a trustful individual accepts the interaction, whereas a suspicious individual opts out of the interaction. If either of the two individuals opt out both individuals remain without an interaction. We show that in the prisoners dilemma optional interactions along with suspicious behaviour facilitates the emergence of trustful cooperation.
AU - Priklopil, Tadeas
AU - Chatterjee, Krishnendu
AU - Nowak, Martin
ID - 744
JF - Journal of Theoretical Biology
SN - 00225193
TI - Optional interactions and suspicious behaviour facilitates trustful cooperation in prisoners dilemma
VL - 433
ER -
TY - JOUR
AB - Fluid flows in nature and applications are frequently subject to periodic velocity modulations. Surprisingly, even for the generic case of flow through a straight pipe, there is little consensus regarding the influence of pulsation on the transition threshold to turbulence: while most studies predict a monotonically increasing threshold with pulsation frequency (i.e. Womersley number, ), others observe a decreasing threshold for identical parameters and only observe an increasing threshold at low . In the present study we apply recent advances in the understanding of transition in steady shear flows to pulsating pipe flow. For moderate pulsation amplitudes we find that the first instability encountered is subcritical (i.e. requiring finite amplitude disturbances) and gives rise to localized patches of turbulence ('puffs') analogous to steady pipe flow. By monitoring the impact of pulsation on the lifetime of turbulence we map the onset of turbulence in parameter space. Transition in pulsatile flow can be separated into three regimes. At small Womersley numbers the dynamics is dominated by the decay turbulence suffers during the slower part of the cycle and hence transition is delayed significantly. As shown in this regime thresholds closely agree with estimates based on a quasi-steady flow assumption only taking puff decay rates into account. The transition point predicted in the zero limit equals to the critical point for steady pipe flow offset by the oscillation Reynolds number (i.e. the dimensionless oscillation amplitude). In the high frequency limit on the other hand, puff lifetimes are identical to those in steady pipe flow and hence the transition threshold appears to be unaffected by flow pulsation. In the intermediate frequency regime the transition threshold sharply drops (with increasing ) from the decay dominated (quasi-steady) threshold to the steady pipe flow level.
AU - Xu, Duo
AU - Warnecke, Sascha
AU - Song, Baofang
AU - Ma, Xingyu
AU - Hof, Björn
ID - 745
JF - Journal of Fluid Mechanics
SN - 00221120
TI - Transition to turbulence in pulsating pipe flow
VL - 831
ER -
TY - JOUR
AB - This special issue of the Journal on Formal Methods in System Design is dedicated to Prof. Helmut Veith, who unexpectedly passed away in March 2016. Helmut Veith was a brilliant researcher, inspiring collaborator, passionate mentor, generous friend, and valued member of the formal methods community. Helmut was not only known for his numerous and influential contributions in the field of automated verification (most prominently his work on Counterexample-Guided Abstraction Refinement [1,2]), but also for his untiring and passionate efforts for the logic community: he co-organized the Vienna Summer of Logic (an event comprising twelve conferences and numerous workshops which attracted thousands of researchers from all over the world), he initiated the Vienna Center for Logic and Algorithms (which promotes international collaboration on logic and algorithms and organizes outreach events such as the LogicLounge), and he coordinated the Doctoral Program on Logical Methods in Computer Science at TU Wien (currently educating more than 40 doctoral students) and a National Research Network on Rigorous Systems Engineering (uniting fifteen researchers in Austria to address the challenge of building reliable and safe computer
systems). With his enthusiasm and commitment, Helmut completely reshaped the Austrian research landscape in the field of logic and verification in his few years as a full professor at TU Wien.
AU - Gottlob, Georg
AU - Henzinger, Thomas A
AU - Weißenbacher, Georg
ID - 743
IS - 2
JF - Formal Methods in System Design
TI - Preface of the special issue in memoriam Helmut Veith
VL - 51
ER -
TY - JOUR
AB - Metabotropic glutamate receptor subtype 5 (mGluR5) is crucially implicated in the pathophysiology of Fragile X Syndrome (FXS); however, its dysfunction at the sub-cellular level, and related synaptic and cognitive phenotypes are unexplored. Here, we probed the consequences of mGluR5/Homer scaffold disruption for mGluR5 cell-surface mobility, synaptic N-methyl-D-Aspartate receptor (NMDAR) function, and behavioral phenotypes in the second-generation Fmr1 knockout (KO) mouse. Using single-molecule tracking, we found that mGluR5 was significantly more mobile at synapses in hippocampal Fmr1 KO neurons, causing an increased synaptic surface co-clustering of mGluR5 and NMDAR. This correlated with a reduced amplitude of synaptic NMDAR currents, a lack of their mGluR5-Activated long-Term depression, and NMDAR/hippocampus dependent cognitive deficits. These synaptic and behavioral phenomena were reversed by knocking down Homer1a in Fmr1 KO mice. Our study provides a mechanistic link between changes of mGluR5 dynamics and pathological phenotypes of FXS, unveiling novel targets for mGluR5-based therapeutics.
AU - Aloisi, Elisabetta
AU - Le Corf, Katy
AU - Dupuis, Julien
AU - Zhang, Pei
AU - Ginger, Melanie
AU - Labrousse, Virginie
AU - Spatuzza, Michela
AU - Georg Haberl, Matthias
AU - Costa, Lara
AU - Shigemoto, Ryuichi
AU - Tappe Theodor, Anke
AU - Drago, Fillippo
AU - Vincenzo Piazza, Pier
AU - Mulle, Christophe
AU - Groc, Laurent
AU - Ciranna, Lucia
AU - Catania, Maria
AU - Frick, Andreas
ID - 746
IS - 1
JF - Nature Communications
SN - 20411723
TI - Altered surface mGluR5 dynamics provoke synaptic NMDAR dysfunction and cognitive defects in Fmr1 knockout mice
VL - 8
ER -
TY - JOUR
AB - Bradykinin (BK), a component of the kallikrein-kininogen-kinin system exerts multiple effects via B1 and B2 receptor activation. In the cardiovascular system, bradykinin has cardioprotective and vasodilator properties. We investigated the effect of BK on cardiac-projecting neurons of nucleus ambiguus, a key site for the parasympathetic cardiac regulation. BK produced a dose-dependent increase in cytosolic Ca2+ concentration. Pretreatment with HOE140, a B2 receptor antagonist, but not with R715, a B1 receptor antagonist, abolished the response to BK. A selective B2 receptor agonist, but not a B1 receptor agonist, elicited an increase in cytosolic Ca2+ similarly to BK. Inhibition of N-type voltage-gated Ca2+ channels with ω-conotoxin GVIA had no effect on the Ca2+ signal produced by BK, while pretreatment with ω-conotoxin MVIIC, a blocker of P/Q-type of Ca2+ channels, significantly diminished the effect of BK. Pretreatment with xestospongin C and 2-aminoethoxydiphenyl borate, antagonists of inositol 1,4,5-trisphosphate receptors, abolished the response to BK. Inhibition of ryanodine receptors reduced the BK-induced Ca2+ increase, while disruption of lysosomal Ca2+ stores with bafilomycin A1 did not affect the response. BK produced a dose-dependent depolarization of nucleus ambiguus neurons, which was prevented by the B2 receptor antagonist. In vivo studies indicate that microinjection of BK into nucleus ambiguus elicited bradycardia in conscious rats via B2 receptors. In summary, in cardiac vagal neurons of nucleus ambiguus, BK activates B2 receptors promoting Ca2+ influx and Ca2+ release from endoplasmic reticulum, and membrane depolarization; these effects are translated in vivo by bradycardia.
AU - Brǎiloiu, Eugen
AU - Mcguire, Matthew
AU - Shuler, Shadaria
AU - Deliu, Elena
AU - Barr, Jeffrey
AU - Abood, Mary
AU - Brailoiu, Gabriela
ID - 747
JF - Neuroscience
SN - 03064522
TI - Modulation of cardiac vagal tone by bradykinin acting on nucleus ambiguus
VL - 365
ER -
TY - CONF
AB - Modern communication technologies allow first responders to contact thousands of potential volunteers simultaneously for support during a crisis or disaster event. However, such volunteer efforts must be well coordinated and monitored, in order to offer an effective relief to the professionals. In this paper we extend earlier work on optimally assigning volunteers to selected landmark locations. In particular, we emphasize the aspect that obtaining good assignments requires not only advanced computational tools, but also a realistic measure of distance between volunteers and landmarks. Specifically, we propose the use of the Open Street Map (OSM) driving distance instead of he previously used flight distance. We find the OSM driving distance to be better aligned with the interests of volunteers and first responders. Furthermore, we show that relying on the flying distance leads to a substantial underestimation of the number of required volunteers, causing negative side effects in case of an actual crisis situation.
AU - Pielorz, Jasmin
AU - Prandtstetter, Matthias
AU - Straub, Markus
AU - Lampert, Christoph
ID - 750
SN - 978-153862714-3
T2 - 2017 IEEE International Conference on Big Data
TI - Optimal geospatial volunteer allocation needs realistic distances
ER -
TY - JOUR
AB - The basement membrane (BM) is a thin layer of extracellular matrix (ECM) beneath nearly all epithelial cell types that is critical for cellular and tissue function. It is composed of numerous components conserved among all bilaterians [1]; however, it is unknown how all of these components are generated and subsequently constructed to form a fully mature BM in the living animal. Although BM formation is thought to simply involve a process of self-assembly [2], this concept suffers from a number of logistical issues when considering its construction in vivo. First, incorporation of BM components appears to be hierarchical [3-5], yet it is unclear whether their production during embryogenesis must also be regulated in a temporal fashion. Second, many BM proteins are produced not only by the cells residing on the BM but also by surrounding cell types [6-9], and it is unclear how large, possibly insoluble protein complexes [10] are delivered into the matrix. Here we exploit our ability to live image and genetically dissect de novo BM formation during Drosophila development. This reveals that there is a temporal hierarchy of BM protein production that is essential for proper component incorporation. Furthermore, we show that BM components require secretion by migrating macrophages (hemocytes) during their developmental dispersal, which is critical for embryogenesis. Indeed, hemocyte migration is essential to deliver a subset of ECM components evenly throughout the embryo. This reveals that de novo BM construction requires a combination of both production and distribution logistics allowing for the timely delivery of core components.
AU - Matsubayashi, Yutaka
AU - Louani, Adam
AU - Dragu, Anca
AU - Sanchez Sanchez, Besaiz
AU - Serna Morales, Eduardo
AU - Yolland, Lawrence
AU - György, Attila
AU - Vizcay, Gema
AU - Fleck, Roland
AU - Heddleston, John
AU - Chew, Teng
AU - Siekhaus, Daria E
AU - Stramer, Brian
ID - 751
IS - 22
JF - Current Biology
SN - 09609822
TI - A moving source of matrix components is essential for De Novo basement membrane formation
VL - 27
ER -
TY - CONF
AB - Consider the following random process: we are given n queues, into which elements of increasing labels are inserted uniformly at random. To remove an element, we pick two queues at random, and remove the element of lower label (higher priority) among the two. The cost of a removal is the rank of the label removed, among labels still present in any of the queues, that is, the distance from the optimal choice at each step. Variants of this strategy are prevalent in state-of-the-art concurrent priority queue implementations. Nonetheless, it is not known whether such implementations provide any rank guarantees, even in a sequential model. We answer this question, showing that this strategy provides surprisingly strong guarantees: Although the single-choice process, where we always insert and remove from a single randomly chosen queue, has degrading cost, going to infinity as we increase the number of steps, in the two choice process, the expected rank of a removed element is O(n) while the expected worst-case cost is O(n log n). These bounds are tight, and hold irrespective of the number of steps for which we run the process. The argument is based on a new technical connection between "heavily loaded" balls-into-bins processes and priority scheduling. Our analytic results inspire a new concurrent priority queue implementation, which improves upon the state of the art in terms of practical performance.
AU - Alistarh, Dan-Adrian
AU - Kopinsky, Justin
AU - Li, Jerry
AU - Nadiradze, Giorgi
ID - 791
SN - 978-145034992-5
T2 - Proceedings of the ACM Symposium on Principles of Distributed Computing
TI - The power of choice in priority scheduling
VL - Part F129314
ER -
TY - JOUR
AB - The chaotic dynamics of low-dimensional systems, such as Lorenz or Rössler flows, is guided by the infinity of periodic orbits embedded in their strange attractors. Whether this is also the case for the infinite-dimensional dynamics of Navier–Stokes equations has long been speculated, and is a topic of ongoing study. Periodic and relative periodic solutions have been shown to be involved in transitions to turbulence. Their relevance to turbulent dynamics – specifically, whether periodic orbits play the same role in high-dimensional nonlinear systems like the Navier–Stokes equations as they do in lower-dimensional systems – is the focus of the present investigation. We perform here a detailed study of pipe flow relative periodic orbits with energies and mean dissipations close to turbulent values. We outline several approaches to reduction of the translational symmetry of the system. We study pipe flow in a minimal computational cell at Re=2500, and report a library of invariant solutions found with the aid of the method of slices. Detailed study of the unstable manifolds of a sample of these solutions is consistent with the picture that relative periodic orbits are embedded in the chaotic saddle and that they guide the turbulent dynamics.
AU - Budanur, Nazmi B
AU - Short, Kimberly
AU - Farazmand, Mohammad
AU - Willis, Ashley
AU - Cvitanović, Predrag
ID - 792
JF - Journal of Fluid Mechanics
SN - 00221120
TI - Relative periodic orbits form the backbone of turbulent pipe flow
VL - 833
ER -
TY - JOUR
AB - Let P be a finite point set in the plane. A cordinary triangle in P is a subset of P consisting of three non-collinear points such that each of the three lines determined by the three points contains at most c points of P . Motivated by a question of Erdös, and answering a question of de Zeeuw, we prove that there exists a constant c > 0such that P contains a c-ordinary triangle, provided that P is not contained in the union of two lines. Furthermore, the number of c-ordinary triangles in P is Ω(| P |).
AU - Fulek, Radoslav
AU - Mojarrad, Hossein
AU - Naszódi, Márton
AU - Solymosi, József
AU - Stich, Sebastian
AU - Szedlák, May
ID - 793
JF - Computational Geometry: Theory and Applications
SN - 09257721
TI - On the existence of ordinary triangles
VL - 66
ER -
TY - JOUR
AB - We show that c-planarity is solvable in quadratic time for flat clustered graphs with three clusters if the combinatorial embedding of the underlying graph is fixed. In simpler graph-theoretical terms our result can be viewed as follows. Given a graph G with the vertex set partitioned into three parts embedded on a 2-sphere, our algorithm decides if we can augment G by adding edges without creating an edge-crossing so that in the resulting spherical graph the vertices of each part induce a connected sub-graph. We proceed by a reduction to the problem of testing the existence of a perfect matching in planar bipartite graphs. We formulate our result in a slightly more general setting of cyclic clustered graphs, i.e., the simple graph obtained by contracting each cluster, where we disregard loops and multi-edges, is a cycle.
AU - Fulek, Radoslav
ID - 794
JF - Computational Geometry: Theory and Applications
TI - C-planarity of embedded cyclic c-graphs
VL - 66
ER -
TY - JOUR
AB - We introduce a common generalization of the strong Hanani–Tutte theorem and the weak Hanani–Tutte theorem: if a graph G has a drawing D in the plane where every pair of independent edges crosses an even number of times, then G has a planar drawing preserving the rotation of each vertex whose incident edges cross each other evenly in D. The theorem is implicit in the proof of the strong Hanani–Tutte theorem by Pelsmajer, Schaefer and Štefankovič. We give a new, somewhat simpler proof.
AU - Fulek, Radoslav
AU - Kynčl, Jan
AU - Pálvölgyi, Dömötör
ID - 795
IS - 3
JF - Electronic Journal of Combinatorics
SN - 10778926
TI - Unified Hanani Tutte theorem
VL - 24
ER -
TY - JOUR
AB - We present the fabrication and characterization of an aluminum transmon qubit on a silicon-on-insulator substrate. Key to the qubit fabrication is the use of an anhydrous hydrofluoric vapor process which selectively removes the lossy silicon oxide buried underneath the silicon device layer. For a 5.6 GHz qubit measured dispersively by a 7.1 GHz resonator, we find T1 = 3.5 μs and T∗2 = 2.2 μs. This process in principle permits the co-fabrication of silicon photonic and mechanical elements, providing a route towards chip-scale integration of electro-opto-mechanical transducers for quantum networking of superconducting microwave quantum circuits. The additional processing steps are compatible with established fabrication techniques for aluminum transmon qubits on silicon.
AU - Keller, Andrew J
AU - Dieterle, Paul
AU - Fang, Michael
AU - Berger, Brett
AU - Fink, Johannes M
AU - Painter, Oskar
ID - 796
IS - 4
JF - Applied Physics Letters
SN - 00036951
TI - Al transmon qubits on silicon on insulator for quantum device integration
VL - 111
ER -
TY - JOUR
AB - Nonreciprocal circuit elements form an integral part of modern measurement and communication systems. Mathematically they require breaking of time-reversal symmetry, typically achieved using magnetic materials and more recently using the quantum Hall effect, parametric permittivity modulation or Josephson nonlinearities. Here we demonstrate an on-chip magnetic-free circulator based on reservoir-engineered electromechanic interactions. Directional circulation is achieved with controlled phase-sensitive interference of six distinct electro-mechanical signal conversion paths. The presented circulator is compact, its silicon-on-insulator platform is compatible with both superconducting qubits and silicon photonics, and its noise performance is close to the quantum limit. With a high dynamic range, a tunable bandwidth of up to 30 MHz and an in situ reconfigurability as beam splitter or wavelength converter, it could pave the way for superconducting qubit processors with multiplexed on-chip signal processing and readout.
AU - Barzanjeh, Shabir
AU - Wulf, Matthias
AU - Peruzzo, Matilda
AU - Kalaee, Mahmoud
AU - Dieterle, Paul
AU - Painter, Oskar
AU - Fink, Johannes M
ID - 798
IS - 1
JF - Nature Communications
SN - 20411723
TI - Mechanical on chip microwave circulator
VL - 8
ER -
TY - JOUR
AB - Phasenübergänge helfen beim Verständnis von Vielteilchensystemen in der Festkörperphysik und Fluiddynamik bis hin zur Teilchenphysik. Unserer internationalen Kollaboration ist es gelungen, einen neuartigen Phasenübergang in einem Quantensystem zu beobachten [1]. In einem Mikrowellenresonator konnte erstmals die spontane Zustandsänderung von undurchsichtig zu transparent nachgewiesen werden.
AU - Fink, Johannes M
ID - 797
IS - 3
JF - Physik in unserer Zeit
TI - Photonenblockade aufgelöst
VL - 48
ER -
TY - JOUR
AB - Membrane traffic at the trans-Golgi network (TGN) is crucial for correctly distributing various membrane proteins to their destination. Polarly localized auxin efflux proteins, including PIN-FORMED1 (PIN1), are dynamically transported between the endosomes and the plasma membrane (PM) in the plant cells. The intracellular trafficking of PIN1 protein is sensitive to a fungal toxin brefeldin A (BFA), which is known to inhibit guanine-nucleotide exchange factors for ADP ribosylation factors (ARF GEFs) such as GNOM. However, the molecular details of the BFA-sensitive trafficking pathway have not been revealed fully. In a previous study, we have identified an Arabidopsis mutant BFA-visualized endocytic trafficking defective 3 (ben3) which exhibited reduced sensitivity to BFA in terms of BFA-induced intracellular PIN1 agglomeration. Here, we show that BEN3 encodes a member of BIG family ARF GEFs, BIG2. Fluorescent proteins tagged BEN3/BIG2 co-localized with markers for TGN / early endosome (EE). Inspection of conditionally induced de novo synthesized PIN1 confirmed that its secretion to the PM is BFA-sensitive and established BEN3/BIG2 as a crucial component of this BFA action at the level of TGN/EE. Furthermore, ben3 mutation alleviated BFA-induced agglomeration of another TGN-localized ARF GEF BEN1/MIN7. Taken together our results suggest that BEN3/BIG2 is an ARF GEF component, which confers BFA sensitivity to the TGN/EE in Arabidopsis.
AU - Kitakura, Saeko
AU - Adamowski, Maciek
AU - Matsuura, Yuki
AU - Santuari, Luca
AU - Kouno, Hirotaka
AU - Arima, Kohei
AU - Hardtke, Christian
AU - Friml, Jirí
AU - Kakimoto, Tatsuo
AU - Tanaka, Hirokazu
ID - 799
IS - 10
JF - Plant and Cell Physiology
SN - 00320781
TI - BEN3/BIG2 ARF GEF is involved in brefeldin a-sensitive trafficking at the trans-Golgi network/early endosome in Arabidopsis thaliana
VL - 58
ER -
TY - JOUR
AB - Gamma oscillations (30–150 Hz) in neuronal networks are associated with the processing and recall of information. We measured local field potentials in the dentate gyrus of freely moving mice and found that gamma activity occurs in bursts, which are highly heterogeneous in their spatial extensions, ranging from focal to global coherent events. Synaptic communication among perisomatic-inhibitory interneurons (PIIs) is thought to play an important role in the generation of hippocampal gamma patterns. However, how neuronal circuits can generate synchronous oscillations at different spatial scales is unknown. We analyzed paired recordings in dentate gyrus slices and show that synaptic signaling at interneuron-interneuron synapses is distance dependent. Synaptic strength declines whereas the duration of inhibitory signals increases with axonal distance among interconnected PIIs. Using neuronal network modeling, we show that distance-dependent inhibition generates multiple highly synchronous focal gamma bursts allowing the network to process complex inputs in parallel in flexibly organized neuronal centers.
AU - Strüber, Michael
AU - Sauer, Jonas
AU - Jonas, Peter M
AU - Bartos, Marlene
ID - 800
IS - 1
JF - Nature Communications
SN - 20411723
TI - Distance-dependent inhibition facilitates focality of gamma oscillations in the dentate gyrus
VL - 8
ER -
TY - JOUR
AB - Eukaryotic cells store their chromosomes in a single nucleus. This is important to maintain genomic integrity, as chromosomes packaged into separate nuclei (micronuclei) are prone to massive DNA damage. During mitosis, higher eukaryotes disassemble their nucleus and release individualized chromosomes for segregation. How numerous chromosomes subsequently reform a single nucleus has remained unclear. Using image-based screening of human cells, we identified barrier-to-autointegration factor (BAF) as a key factor guiding membranes to form a single nucleus. Unexpectedly, nuclear assembly does not require BAF?s association with inner nuclear membrane proteins but instead relies on BAF?s ability to bridge distant DNA sites. Live-cell imaging and in vitro reconstitution showed that BAF enriches around the mitotic chromosome ensemble to induce a densely cross-bridged chromatin layer that is mechanically stiff and limits membranes to the surface. Our study reveals that BAF-mediated changes in chromosome mechanics underlie nuclear assembly with broad implications for proper genome function.
AU - Samwer, Matthias
AU - Schneider, Maximilian
AU - Hoefler, Rudolf
AU - Schmalhorst, Philipp S
AU - Jude, Julian
AU - Zuber, Johannes
AU - Gerlic, Daniel
ID - 803
IS - 5
JF - Cell
SN - 00928674
TI - DNA cross-bridging shapes a single nucleus from a set of mitotic chromosomes
VL - 170
ER -
TY - JOUR
AB - Polysaccharides (carbohydrates) are key regulators of a large number of cell biological processes. However, precise biochemical or genetic manipulation of these often complex structures is laborious and hampers experimental structure–function studies. Molecular Dynamics (MD) simulations provide a valuable alternative tool to generate and test hypotheses on saccharide function. Yet, currently used MD force fields often overestimate the aggregation propensity of polysaccharides, affecting the usability of those simulations. Here we tested MARTINI, a popular coarse-grained (CG) force field for biological macromolecules, for its ability to accurately represent molecular forces between saccharides. To this end, we calculated a thermodynamic solution property, the second virial coefficient of the osmotic pressure (B22). Comparison with light scattering experiments revealed a nonphysical aggregation of a prototypical polysaccharide in MARTINI, pointing at an imbalance of the nonbonded solute–solute, solute–water, and water–water interactions. This finding also applies to smaller oligosaccharides which were all found to aggregate in simulations even at moderate concentrations, well below their solubility limit. Finally, we explored the influence of the Lennard-Jones (LJ) interaction between saccharide molecules and propose a simple scaling of the LJ interaction strength that makes MARTINI more reliable for the simulation of saccharides.
AU - Schmalhorst, Philipp S
AU - Deluweit, Felix
AU - Scherrers, Roger
AU - Heisenberg, Carl-Philipp J
AU - Sikora, Mateusz K
ID - 804
IS - 10
JF - Journal of Chemical Theory and Computation
SN - 15499618
TI - Overcoming the limitations of the MARTINI force field in simulations of polysaccharides
VL - 13
ER -
TY - JOUR
AB - During corticogenesis, distinct classes of neurons are born from progenitor cells located in the ventricular and subventricular zones, from where they migrate towards the pial surface to assemble into highly organized layer-specific circuits. However, the precise and coordinated transcriptional network activity defining neuronal identity is still not understood. Here, we show that genetic depletion of the basic helix-loop-helix (bHLH) transcription factor E2A splice variant E47 increased the number of Tbr1-positive deep layer and Satb2-positive upper layer neurons at E14.5, while depletion of the alternatively spliced E12 variant did not affect layer-specific neurogenesis. While ChIP-Seq identified a big overlap for E12- and E47-specific binding sites in embryonic NSCs, including sites at the cyclin-dependent kinase inhibitor (CDKI) Cdkn1c gene locus, RNA-Seq revealed a unique transcriptional regulation by each splice variant. E47 activated the expression of the CDKI Cdkn1c through binding to a distal enhancer. Finally, overexpression of E47 in embryonic NSCs in vitro impaired neurite outgrowth and E47 overexpression in vivo by in utero electroporation disturbed proper layer-specific neurogenesis and upregulated p57(KIP2) expression. Overall, this study identified E2A target genes in embryonic NSCs and demonstrates that E47 regulates neuronal differentiation via p57(KIP2).
AU - Pfurr, Sabrina
AU - Chu, Yu
AU - Bohrer, Christian
AU - Greulich, Franziska
AU - Beattie, Robert J
AU - Mammadzada, Könül
AU - Hils, Miriam
AU - Arnold, Sebastian
AU - Taylor, Verdon
AU - Schachtrup, Kristina
AU - Uhlenhaut, N Henriette
AU - Schachtrup, Christian
ID - 805
JF - Development
TI - The E2A splice variant E47 regulates the differentiation of projection neurons via p57(KIP2) during cortical development
VL - 144
ER -
TY - JOUR
AB - On January the 1st, 2016 a new agreement between 32 Austrian scientific libraries and the publisher Springer took its effect: this deal covers accessing the licensed content on the one hand, and publishing open access on the other hand. More than 1000 papers by Austrian authors were published open access at Springer in the first year alone. The working group "Springer Compact Evaluierung" made the data for these articles available via the platform OpenAPC and would like to use this opportunity to give a short account of what this publishing agreement actually entails and the working group intends to do.
AU - Andrae, Magdalena
AU - Villányi, Márton
ID - 807
IS - 2
JF - Mitteilungen der Vereinigung Österreichischer Bibliothekarinnen und Bibliothekare
SN - 10222588
TI - Der Springer Compact-Deal – Ein erster Einblick in die Evaluierung einer Offsetting-Vereinbarung
VL - 70
ER -
TY - JOUR
AB - Polymicrobial infections constitute small ecosystems that accommodate several bacterial species. Commonly, these bacteria are investigated in isolation. However, it is unknown to what extent the isolates interact and whether their interactions alter bacterial growth and ecosystem resilience in the presence and absence of antibiotics. We quantified the complete ecological interaction network for 72 bacterial isolates collected from 23 individuals diagnosed with polymicrobial urinary tract infections and found that most interactions cluster based on evolutionary relatedness. Statistical network analysis revealed that competitive and cooperative reciprocal interactions are enriched in the global network, while cooperative interactions are depleted in the individual host community networks. A population dynamics model parameterized by our measurements suggests that interactions restrict community stability, explaining the observed species diversity of these communities. We further show that the clinical isolates frequently protect each other from clinically relevant antibiotics. Together, these results highlight that ecological interactions are crucial for the growth and survival of bacteria in polymicrobial infection communities and affect their assembly and resilience.
AU - De Vos, Marjon
AU - Zagórski, Marcin P
AU - Mcnally, Alan
AU - Bollenbach, Mark Tobias
ID - 822
IS - 40
JF - PNAS
SN - 00278424
TI - Interaction networks, ecological stability, and collective antibiotic tolerance in polymicrobial infections
VL - 114
ER -
TY - JOUR
AB - The resolution of a linear system with positive integer variables is a basic yet difficult computational problem with many applications. We consider sparse uncorrelated random systems parametrised by the density c and the ratio α=N/M between number of variables N and number of constraints M. By means of ensemble calculations we show that the space of feasible solutions endows a Van-Der-Waals phase diagram in the plane (c, α). We give numerical evidence that the associated computational problems become more difficult across the critical point and in particular in the coexistence region.
AU - Colabrese, Simona
AU - De Martino, Daniele
AU - Leuzzi, Luca
AU - Marinari, Enzo
ID - 823
IS - 9
JF - Journal of Statistical Mechanics: Theory and Experiment
SN - 17425468
TI - Phase transitions in integer linear problems
VL - 2017
ER -
TY - JOUR
AB - In shear flows at transitional Reynolds numbers, localized patches of turbulence, known as puffs, coexist with the laminar flow. Recently, Avila et al. (Phys. Rev. Lett., vol. 110, 2013, 224502) discovered two spatially localized relative periodic solutions for pipe flow, which appeared in a saddle-node bifurcation at low Reynolds number. Combining slicing methods for continuous symmetry reduction with Poincaré sections for the first time in a shear flow setting, we compute and visualize the unstable manifold of the lower-branch solution and show that it extends towards the neighbourhood of the upper-branch solution. Surprisingly, this connection even persists far above the bifurcation point and appears to mediate the first stage of the puff generation: amplification of streamwise localized fluctuations. When the state-space trajectories on the unstable manifold reach the vicinity of the upper branch, corresponding fluctuations expand in space and eventually take the usual shape of a puff.
AU - Budanur, Nazmi B
AU - Hof, Björn
ID - 824
JF - Journal of Fluid Mechanics
SN - 00221120
TI - Heteroclinic path to spatially localized chaos in pipe flow
VL - 827
ER -
TY - JOUR
AB - What data is needed about data? Describing the process to answer this question for the institutional data repository IST DataRep.
AU - Petritsch, Barbara
ID - 825
IS - 2
JF - Mitteilungen der Vereinigung Österreichischer Bibliothekarinnen & Bibliothekare
SN - 10222588
TI - Metadata for research data in practice
VL - 70
ER -
TY - CHAP
AB - The advent of high-throughput technologies and the concurrent advances in information sciences have led to a data revolution in biology. This revolution is most significant in molecular biology, with an increase in the number and scale of the “omics” projects over the last decade. Genomics projects, for example, have produced impressive advances in our knowledge of the information concealed into genomes, from the many genes that encode for the proteins that are responsible for most if not all cellular functions, to the noncoding regions that are now known to provide regulatory functions. Proteomics initiatives help to decipher the role of post-translation modifications on the protein structures and provide maps of protein-protein interactions, while functional genomics is the field that attempts to make use of the data produced by these projects to understand protein functions. The biggest challenge today is to assimilate the wealth of information provided by these initiatives into a conceptual framework that will help us decipher life. For example, the current views of the relationship between protein structure and function remain fragmented. We know of their sequences, more and more about their structures, we have information on their biological activities, but we have difficulties connecting this dotted line into an informed whole. We lack the experimental and computational tools for directly studying protein structure, function, and dynamics at the molecular and supra-molecular levels. In this chapter, we review some of the current developments in building the computational tools that are needed, focusing on the role that geometry and topology play in these efforts. One of our goals is to raise the general awareness about the importance of geometric methods in elucidating the mysterious foundations of our very existence. Another goal is the broadening of what we consider a geometric algorithm. There is plenty of valuable no-man’s-land between combinatorial and numerical algorithms, and it seems opportune to explore this land with a computational-geometric frame of mind.
AU - Edelsbrunner, Herbert
AU - Koehl, Patrice
ED - Toth, Csaba
ED - O'Rourke, Joseph
ED - Goodman, Jacob
ID - 84
T2 - Handbook of Discrete and Computational Geometry, Third Edition
TI - Computational topology for structural molecular biology
ER -
TY - JOUR
AB - Cytosine methylation regulates essential genome functions across eukaryotes, but the fundamental question of whether nucleosomal or naked DNA is the preferred substrate of plant and animal methyltransferases remains unresolved. Here, we show that genetic inactivation of a single DDM1/Lsh family nucleosome remodeler biases methylation toward inter-nucleosomal linker DNA in Arabidopsis thaliana and mouse. We find that DDM1 enables methylation of DNA bound to the nucleosome, suggesting that nucleosome-free DNA is the preferred substrate of eukaryotic methyltransferases in vivo. Furthermore, we show that simultaneous mutation of DDM1 and linker histone H1 in Arabidopsis reproduces the strong linker-specific methylation patterns of species that diverged from flowering plants and animals over a billion years ago. Our results indicate that in the absence of remodeling, nucleosomes are strong barriers to DNA methyltransferases. Linker-specific methylation can evolve simply by breaking the connection between nucleosome remodeling and DNA methylation.
AU - Lyons, David B
AU - Zilberman, Daniel
ID - 9445
JF - eLife
TI - DDM1 and Lsh remodelers allow methylation of DNA wrapped in nucleosomes
VL - 6
ER -
TY - CHAP
AB - Small molecule biosensors based on Forster resonance energy transfer (FRET) enable small molecule signaling to be monitored with high spatial and temporal resolution in complex cellular environments. FRET sensors can be constructed by fusing a pair of fluorescent proteins to a suitable recognition domain, such as a member of the solute-binding protein (SBP) superfamily. However, naturally occurring SBPs may be unsuitable for incorporation into FRET sensors due to their low thermostability, which may preclude imaging under physiological conditions, or because the positions of their N- and C-termini may be suboptimal for fusion of fluorescent proteins, which may limit the dynamic range of the resulting sensors. Here, we show how these problems can be overcome using ancestral protein reconstruction and circular permutation. Ancestral protein reconstruction, used as a protein engineering strategy, leverages phylogenetic information to improve the thermostability of proteins, while circular permutation enables the termini of an SBP to be repositioned to maximize the dynamic range of the resulting FRET sensor. We also provide a protocol for cloning the engineered SBPs into FRET sensor constructs using Golden Gate assembly and discuss considerations for in situ characterization of the FRET sensors.
AU - Clifton, Ben
AU - Whitfield, Jason
AU - Sanchez Romero, Inmaculada
AU - Herde, Michel
AU - Henneberger, Christian
AU - Janovjak, Harald L
AU - Jackson, Colin
ED - Stein, Viktor
ID - 957
SN - 10643745
T2 - Synthetic Protein Switches
TI - Ancestral protein reconstruction and circular permutation for improving the stability and dynamic range of FRET sensors
VL - 1596
ER -
TY - CONF
AB - Network games are widely used as a model for selfish resource-allocation problems. In the classical model, each player selects a path connecting her source and target vertex. The cost of traversing an edge depends on the number of players that traverse it. Thus, it abstracts the fact that different users may use a resource at different times and for different durations, which plays an important role in defining the costs of the users in reality. For example, when transmitting packets in a communication network, routing traffic in a road network, or processing a task in a production system, the traversal of the network involves an inherent delay, and so sharing and congestion of resources crucially depends on time. We study timed network games , which add a time component to network games. Each vertex v in the network is associated with a cost function, mapping the load on v to the price that a player pays for staying in v for one time unit with this load. In addition, each edge has a guard, describing time intervals in which the edge can be traversed, forcing the players to spend time on vertices. Unlike earlier work that add a time component to network games, the time in our model is continuous and cannot be discretized. In particular, players have uncountably many strategies, and a game may have uncountably many pure Nash equilibria. We study properties of timed network games with cost-sharing or congestion cost functions: their stability, equilibrium inefficiency, and complexity. In particular, we show that the answer to the question whether we can restrict attention to boundary strategies, namely ones in which edges are traversed only at the boundaries of guards, is mixed.
AU - Avni, Guy
AU - Guha, Shibashis
AU - Kupferman, Orna
ID - 963
SN - 18688969
TI - Timed network games with clocks
VL - 83
ER -
TY - GEN
AB - Across the nervous system, certain population spiking patterns are observed far more frequently than others. A hypothesis about this structure is that these collective activity patterns function as population codewords–collective modes–carrying information distinct from that of any single cell. We investigate this phenomenon in recordings of ∼150 retinal ganglion cells, the retina’s output. We develop a novel statistical model that decomposes the population response into modes; it predicts the distribution of spiking activity in the ganglion cell population with high accuracy. We found that the modes represent localized features of the visual stimulus that are distinct from the features represented by single neurons. Modes form clusters of activity states that are readily discriminated from one another. When we repeated the same visual stimulus, we found that the same mode was robustly elicited. These results suggest that retinal ganglion cells’ collective signaling is endowed with a form of error-correcting code–a principle that may hold in brain areas beyond retina.
AU - Prentice, Jason
AU - Marre, Olivier
AU - Ioffe, Mark
AU - Loback, Adrianna
AU - Tkačik, Gašper
AU - Berry, Michael
ID - 9709
TI - Data from: Error-robust modes of the retinal population code
ER -
TY - JOUR
AB - While we have good understanding of bacterial metabolism at the population level, we know little about the metabolic behavior of individual cells: do single cells in clonal populations sometimes specialize on different metabolic pathways? Such metabolic specialization could be driven by stochastic gene expression and could provide individual cells with growth benefits of specialization. We measured the degree of phenotypic specialization in two parallel metabolic pathways, the assimilation of glucose and arabinose. We grew Escherichia coli in chemostats, and used isotope-labeled sugars in combination with nanometer-scale secondary ion mass spectrometry and mathematical modeling to quantify sugar assimilation at the single-cell level. We found large variation in metabolic activities between single cells, both in absolute assimilation and in the degree to which individual cells specialize in the assimilation of different sugars. Analysis of transcriptional reporters indicated that this variation was at least partially based on cell-to-cell variation in gene expression. Metabolic differences between cells in clonal populations could potentially reduce metabolic incompatibilities between different pathways, and increase the rate at which parallel reactions can be performed.
AU - Nikolic, Nela
AU - Schreiber, Frank
AU - Dal Co, Alma
AU - Kiviet, Daniel
AU - Bergmiller, Tobias
AU - Littmann, Sten
AU - Kuypers, Marcel
AU - Ackermann, Martin
ID - 541
IS - 12
JF - PLoS Genetics
SN - 15537390
TI - Cell-to-cell variation and specialization in sugar metabolism in clonal bacterial populations
VL - 13
ER -
TY - GEN
AB - information on culture conditions, phage mutagenesis, verification and lysate preparation; Raw data
AU - Pleska, Maros
AU - Guet, Calin C
ID - 9847
TI - Supplementary materials and methods; Full data set from effects of mutations in phage restriction sites during escape from restriction–modification
ER -
TY - GEN
AB - Estimates of 13 C-arabinose and 2 H-glucose uptake from the fractions of heavy isotopes measured in single cells
AU - Nikolic, Nela
AU - Schreiber, Frank
AU - Dal Co, Alma
AU - Kiviet, Daniel
AU - Bergmiller, Tobias
AU - Littmann, Sten
AU - Kuypers, Marcel
AU - Ackermann, Martin
ID - 9845
TI - Mathematical model
ER -
TY - GEN
AB - This text provides additional information about the model, a derivation of the analytic results in Eq (4), and details about simulations of an additional parameter set.
AU - Lukacisinova, Marta
AU - Novak, Sebastian
AU - Paixao, Tiago
ID - 9849
TI - Modelling and simulation details
ER -
TY - GEN
AB - In this text, we discuss how a cost of resistance and the possibility of lethal mutations impact our model.
AU - Lukacisinova, Marta
AU - Novak, Sebastian
AU - Paixao, Tiago
ID - 9850
TI - Extensions of the model
ER -
TY - GEN
AU - Nikolic, Nela
AU - Schreiber, Frank
AU - Dal Co, Alma
AU - Kiviet, Daniel
AU - Bergmiller, Tobias
AU - Littmann, Sten
AU - Kuypers, Marcel
AU - Ackermann, Martin
ID - 9846
TI - Supplementary methods
ER -
TY - JOUR
AB - In order to respond reliably to specific features of their environment, sensory neurons need to integrate multiple incoming noisy signals. Crucially, they also need to compete for the interpretation of those signals with other neurons representing similar features. The form that this competition should take depends critically on the noise corrupting these signals. In this study we show that for the type of noise commonly observed in sensory systems, whose variance scales with the mean signal, sensory neurons should selectively divide their input signals by their predictions, suppressing ambiguous cues while amplifying others. Any change in the stimulus context alters which inputs are suppressed, leading to a deep dynamic reshaping of neural receptive fields going far beyond simple surround suppression. Paradoxically, these highly variable receptive fields go alongside and are in fact required for an invariant representation of external sensory features. In addition to offering a normative account of context-dependent changes in sensory responses, perceptual inference in the presence of signal-dependent noise accounts for ubiquitous features of sensory neurons such as divisive normalization, gain control and contrast dependent temporal dynamics.
AU - Chalk, Matthew J
AU - Masset, Paul
AU - Gutkin, Boris
AU - Denève, Sophie
ID - 680
IS - 6
JF - PLoS Computational Biology
SN - 1553734X
TI - Sensory noise predicts divisive reshaping of receptive fields
VL - 13
ER -
TY - GEN
AB - Based on the intuitive derivation of the dynamics of SIM allele frequency pM in the main text, we present a heuristic prediction for the long-term SIM allele frequencies with χ > 1 stresses and compare it to numerical simulations.
AU - Lukacisinova, Marta
AU - Novak, Sebastian
AU - Paixao, Tiago
ID - 9851
TI - Heuristic prediction for multiple stresses
ER -
TY - GEN
AB - We show how different combination strategies affect the fraction of individuals that are multi-resistant.
AU - Lukacisinova, Marta
AU - Novak, Sebastian
AU - Paixao, Tiago
ID - 9852
TI - Resistance frequencies for different combination strategies
ER -
TY - GEN
AB - Includes derivation of optimal estimation algorithm, generalisation to non-poisson noise statistics, correlated input noise, and implementation of in a multi-layer neural network.
AU - Chalk, Matthew J
AU - Masset, Paul
AU - Gutkin, Boris
AU - Denève, Sophie
ID - 9855
TI - Supplementary appendix
ER -
TY - CONF
AB - Recently there has been a proliferation of automated program repair (APR) techniques, targeting various programming languages. Such techniques can be generally classified into two families: syntactic- and semantics-based. Semantics-based APR, on which we focus, typically uses symbolic execution to infer semantic constraints and then program synthesis to construct repairs conforming to them. While syntactic-based APR techniques have been shown successful on bugs in real-world programs written in both C and Java, semantics-based APR techniques mostly target C programs. This leaves empirical comparisons of the APR families not fully explored, and developers without a Java-based semantics APR technique. We present JFix, a semantics-based APR framework that targets Java, and an associated Eclipse plugin. JFix is implemented atop Symbolic PathFinder, a well-known symbolic execution engine for Java programs. It extends one particular APR technique (Angelix), and is designed to be sufficiently generic to support a variety of such techniques. We demonstrate that semantics-based APR can indeed efficiently and effectively repair a variety of classes of bugs in large real-world Java programs. This supports our claim that the framework can both support developers seeking semantics-based repair of bugs in Java programs, as well as enable larger scale empirical studies comparing syntactic- and semantics-based APR targeting Java. The demonstration of our tool is available via the project website at: https://xuanbachle.github.io/semanticsrepair/
AU - Le, Xuan
AU - Chu, Duc Hiep
AU - Lo, David
AU - Le Goues, Claire
AU - Visser, Willem
ID - 941
T2 - Proceedings of the 26th ACM SIGSOFT International Symposium on Software Testing and Analysis
TI - JFIX: Semantics-based repair of Java programs via symbolic PathFinder
ER -
TY - JOUR
AB - Methylation in the bodies of active genes is common in animals and vascular plants. Evolutionary patterns indicate homeostatic functions for this type of methylation.
AU - Zilberman, Daniel
ID - 9506
IS - 1
JF - Genome Biology
SN - 1474-760X
TI - An evolutionary case for functional gene body methylation in plants and animals
VL - 18
ER -
TY - CHAP
AB - Biosensors that exploit Forster resonance energy transfer (FRET) can be used to visualize biological and physiological processes and are capable of providing detailed information in both spatial and temporal dimensions. In a FRET-based biosensor, substrate binding is associated with a change in the relative positions of two fluorophores, leading to a change in FRET efficiency that may be observed in the fluorescence spectrum. As a result, their design requires a ligand-binding protein that exhibits a conformational change upon binding. However, not all ligand-binding proteins produce responsive sensors upon conjugation to fluorescent proteins or dyes, and identifying the optimum locations for the fluorophores often involves labor-intensive iterative design or high-throughput screening. Combining the genetic fusion of a fluorescent protein to the ligand-binding protein with site-specific covalent attachment of a fluorescent dye can allow fine control over the positions of the two fluorophores, allowing the construction of very sensitive sensors. This relies upon the accurate prediction of the locations of the two fluorophores in bound and unbound states. In this chapter, we describe a method for computational identification of dye-attachment sites that allows the use of cysteine modification to attach synthetic dyes that can be paired with a fluorescent protein for the purposes of creating FRET sensors.
AU - Mitchell, Joshua
AU - Zhang, William
AU - Herde, Michel
AU - Henneberger, Christian
AU - Janovjak, Harald L
AU - O'Mara, Megan
AU - Jackson, Colin
ED - Stein, Viktor
ID - 958
SN - 10643745
T2 - Synthetic Protein Switches
TI - Method for developing optical sensors using a synthetic dye fluorescent protein FRET pair and computational modeling and assessment
VL - 1596
ER -
TY - GEN
AB - Branching morphogenesis of the epithelial ureteric bud forms the renal collecting duct system and is critical for normal nephron number, while low nephron number is implicated in hypertension and renal disease. Ureteric bud growth and branching requires GDNF signaling from the surrounding mesenchyme to cells at the ureteric bud tips, via the Ret receptor tyrosine kinase and coreceptor Gfrα1; Ret signaling up-regulates transcription factors Etv4 and Etv5, which are also critical for branching. Despite extensive knowledge of the genetic control of these events, it is not understood, at the cellular level, how renal branching morphogenesis is achieved or how Ret signaling influences epithelial cell behaviors to promote this process. Analysis of chimeric embryos previously suggested a role for Ret signaling in promoting cell rearrangements in the nephric duct, but this method was unsuited to study individual cell behaviors during ureteric bud branching. Here, we use Mosaic Analysis with Double Markers (MADM), combined with organ culture and time-lapse imaging, to trace the movements and divisions of individual ureteric bud tip cells. We first examine wild-type clones and then Ret or Etv4 mutant/wild-type clones in which the mutant and wild-type sister cells are differentially and heritably marked by green and red fluorescent proteins. We find that, in normal kidneys, most individual tip cells behave as self-renewing progenitors, some of whose progeny remain at the tips while others populate the growing UB trunks. In Ret or Etv4 MADM clones, the wild-type cells generated at a UB tip are much more likely to remain at, or move to, the new tips during branching and elongation, while their Ret−/− or Etv4−/− sister cells tend to lag behind and contribute only to the trunks. By tracking successive mitoses in a cell lineage, we find that Ret signaling has little effect on proliferation, in contrast to its effects on cell movement. Our results show that Ret/Etv4 signaling promotes directed cell movements in the ureteric bud tips, and suggest a model in which these cell movements mediate branching morphogenesis.
AU - Riccio, Paul
AU - Cebrián, Christina
AU - Zong, Hui
AU - Hippenmeyer, Simon
AU - Costantini, Frank
ID - 9707
TI - Data from: Ret and Etv4 promote directed movements of progenitor cells during renal branching morphogenesis
ER -
TY - GEN
AU - Nikolic, Nela
AU - Schreiber, Frank
AU - Dal Co, Alma
AU - Kiviet, Daniel
AU - Bergmiller, Tobias
AU - Littmann, Sten
AU - Kuypers, Marcel
AU - Ackermann, Martin
ID - 9844
TI - Source data for figures and tables
ER -
TY - GEN
AU - Schlögl, Alois
AU - Kiss, Janos
ID - 12905
T2 - AHPC17 – Austrian HPC Meeting 2017
TI - Scientific Computing at IST Austria
ER -
TY - CONF
AB - Transforming deterministic ω
-automata into deterministic parity automata is traditionally done using variants of appearance records. We present a more efficient variant of this approach, tailored to Rabin automata, and several optimizations applicable to all appearance records. We compare the methods experimentally and find out that our method produces smaller automata than previous approaches. Moreover, the experiments demonstrate the potential of our method for LTL synthesis, using LTL-to-Rabin translators. It leads to significantly smaller parity automata when compared to state-of-the-art approaches on complex formulae.
AU - Kretinsky, Jan
AU - Meggendorfer, Tobias
AU - Waldmann, Clara
AU - Weininger, Maximilian
ID - 13160
SN - 0302-9743
T2 - Tools and Algorithms for the Construction and Analysis of Systems
TI - Index appearance record for transforming Rabin automata into parity automata
VL - 10205
ER -
TY - CONF
AB - Two-player games on graphs are widely studied in formal methods as they model the interaction between a system and its environment. The game is played by moving a token throughout a graph to produce an infinite path. There are several common modes to determine how the players move the token through the graph; e.g., in turn-based games the players alternate turns in moving the token. We study the bidding mode of moving the token, which, to the best of our knowledge, has never been studied in infinite-duration games. Both players have separate budgets, which sum up to $1$. In each turn, a bidding takes place. Both players submit bids simultaneously, and a bid is legal if it does not exceed the available budget. The winner of the bidding pays his bid to the other player and moves the token. For reachability objectives, repeated bidding games have been studied and are called Richman games. There, a central question is the existence and computation of threshold budgets; namely, a value t\in [0,1] such that if\PO's budget exceeds $t$, he can win the game, and if\PT's budget exceeds 1-t, he can win the game. We focus on parity games and mean-payoff games. We show the existence of threshold budgets in these games, and reduce the problem of finding them to Richman games. We also determine the strategy-complexity of an optimal strategy. Our most interesting result shows that memoryless strategies suffice for mean-payoff bidding games.
AU - Avni, Guy
AU - Henzinger, Thomas A
AU - Chonev, Ventsislav K
ID - 950
SN - 1868-8969
TI - Infinite-duration bidding games
VL - 85
ER -
TY - CONF
AB - Given a triangulation of a point set in the plane, a flip deletes an edge e whose removal leaves a convex quadrilateral, and replaces e by the opposite diagonal of the quadrilateral. It is well known that any triangulation of a point set can be reconfigured to any other triangulation by some sequence of flips. We explore this question in the setting where each edge of a triangulation has a label, and a flip transfers the label of the removed edge to the new edge. It is not true that every labelled triangulation of a point set can be reconfigured to every other labelled triangulation via a sequence of flips, but we characterize when this is possible. There is an obvious necessary condition: for each label l, if edge e has label l in the first triangulation and edge f has label l in the second triangulation, then there must be some sequence of flips that moves label l from e to f, ignoring all other labels. Bose, Lubiw, Pathak and Verdonschot formulated the Orbit Conjecture, which states that this necessary condition is also sufficient, i.e. that all labels can be simultaneously mapped to their destination if and only if each label individually can be mapped to its destination. We prove this conjecture. Furthermore, we give a polynomial-time algorithm to find a sequence of flips to reconfigure one labelled triangulation to another, if such a sequence exists, and we prove an upper bound of O(n7) on the length of the flip sequence. Our proof uses the topological result that the sets of pairwise non-crossing edges on a planar point set form a simplicial complex that is homeomorphic to a high-dimensional ball (this follows from a result of Orden and Santos; we give a different proof based on a shelling argument). The dual cell complex of this simplicial ball, called the flip complex, has the usual flip graph as its 1-skeleton. We use properties of the 2-skeleton of the flip complex to prove the Orbit Conjecture.
AU - Lubiw, Anna
AU - Masárová, Zuzana
AU - Wagner, Uli
ID - 683
TI - A proof of the orbit conjecture for flipping edge labelled triangulations
VL - 77
ER -
TY - JOUR
AB - DNA methylation regulates eukaryotic gene expression and is extensively reprogrammed during animal development. However, whether developmental methylation reprogramming during the sporophytic life cycle of flowering plants regulates genes is presently unknown. Here we report a distinctive gene-targeted RNA-directed DNA methylation (RdDM) activity in the Arabidopsis thaliana male sexual lineage that regulates gene expression in meiocytes. Loss of sexual-lineage-specific RdDM causes mis-splicing of the MPS1 gene (also known as PRD2), thereby disrupting meiosis. Our results establish a regulatory paradigm in which de novo methylation creates a cell-lineage-specific epigenetic signature that controls gene expression and contributes to cellular function in flowering plants.
AU - Walker, James
AU - Gao, Hongbo
AU - Zhang, Jingyi
AU - Aldridge, Billy
AU - Vickers, Martin
AU - Higgins, James D.
AU - Feng, Xiaoqi
ID - 12193
IS - 1
JF - Nature Genetics
KW - Genetics
SN - 1061-4036
TI - Sexual-lineage-specific DNA methylation regulates meiosis in Arabidopsis
VL - 50
ER -
TY - THES
AB - This dissertation concerns the automatic verification of probabilistic systems and programs with arrays by statistical and logical methods. Although statistical and logical methods are different in nature, we show that they can be successfully combined for system analysis. In the first part of the dissertation we present a new statistical algorithm for the verification of probabilistic systems with respect to unbounded properties, including linear temporal logic. Our algorithm often performs faster than the previous approaches, and at the same time requires less information about the system. In addition, our method can be generalized to unbounded quantitative properties such as mean-payoff bounds. In the second part, we introduce two techniques for comparing probabilistic systems. Probabilistic systems are typically compared using the notion of equivalence, which requires the systems to have the equal probability of all behaviors. However, this notion is often too strict, since probabilities are typically only empirically estimated, and any imprecision may break the relation between processes. On the one hand, we propose to replace the Boolean notion of equivalence by a quantitative distance of similarity. For this purpose, we introduce a statistical framework for estimating distances between Markov chains based on their simulation runs, and we investigate which distances can be approximated in our framework. On the other hand, we propose to compare systems with respect to a new qualitative logic, which expresses that behaviors occur with probability one or a positive probability. This qualitative analysis is robust with respect to modeling errors and applicable to many domains. In the last part, we present a new quantifier-free logic for integer arrays, which allows us to express counting. Counting properties are prevalent in array-manipulating programs, however they cannot be expressed in the quantified fragments of the theory of arrays. We present a decision procedure for our logic, and provide several complexity results.
AU - Daca, Przemyslaw
ID - 1155
SN - 2663-337X
TI - Statistical and logical methods for property checking
ER -
TY - THES
AB - Bacteria and their pathogens – phages – are the most abundant living entities on Earth. Throughout their coevolution, bacteria have evolved multiple immune systems to overcome the ubiquitous threat from the phages. Although the molecu- lar details of these immune systems’ functions are relatively well understood, their epidemiological consequences for the phage-bacterial communities have been largely neglected. In this thesis we employed both experimental and theoretical methods to explore whether herd and social immunity may arise in bacterial popu- lations. Using our experimental system consisting of Escherichia coli strains with a CRISPR based immunity to the T7 phage we show that herd immunity arises in phage-bacterial communities and that it is accentuated when the populations are spatially structured. By fitting a mathematical model, we inferred expressions for the herd immunity threshold and the velocity of spread of a phage epidemic in partially resistant bacterial populations, which both depend on the bacterial growth rate, phage burst size and phage latent period. We also investigated the poten- tial for social immunity in Streptococcus thermophilus and its phage 2972 using a bioinformatic analysis of potentially coding short open reading frames with a signalling signature, encoded within the CRISPR associated genes. Subsequently, we tested one identified potentially signalling peptide and found that its addition to a phage-challenged culture increases probability of survival of bacteria two fold, although the results were only marginally significant. Together, these results demonstrate that the ubiquitous arms races between bacteria and phages have further consequences at the level of the population.
AU - Payne, Pavel
ID - 6291
SN - 2663-337X
TI - Bacterial herd and social immunity to phages
ER -
TY - JOUR
AB - Restriction–modification systems are widespread genetic elements that protect bacteria from bacteriophage infections by recognizing and cleaving heterologous DNA at short, well-defined sequences called restriction sites. Bioinformatic evidence shows that restriction sites are significantly underrepresented in bacteriophage genomes, presumably because bacteriophages with fewer restriction sites are more likely to escape cleavage by restriction–modification systems. However, how mutations in restriction sites affect the likelihood of bacteriophage escape is unknown. Using the bacteriophage l and the restriction–modification system EcoRI, we show that while mutation effects at different restriction sites are unequal, they are independent. As a result, the probability of bacteriophage escape increases with each mutated restriction site. Our results experimentally support the role of restriction site avoidance as a response to selection imposed by restriction–modification systems and offer an insight into the events underlying the process of bacteriophage escape.
AU - Pleska, Maros
AU - Guet, Calin C
ID - 561
IS - 12
JF - Biology Letters
SN - 1744-9561
TI - Effects of mutations in phage restriction sites during escape from restriction–modification
VL - 13
ER -
TY - THES
AB - Antibiotics have diverse effects on bacteria, including massive changes in bacterial gene expression. Whereas the gene expression changes under many antibiotics have been measured, the temporal organization of these responses and their dependence on the bacterial growth rate are unclear. As described in Chapter 1, we quantified the temporal gene expression changes in the bacterium Escherichia coli in response to the sudden exposure to antibiotics using a fluorescent reporter library and a robotic system. Our data show temporally structured gene expression responses, with response times for individual genes ranging from tens of minutes to several hours. We observed that many stress response genes were activated in response to antibiotics. As certain stress responses cross-protect bacteria from other stressors, we then asked whether cellular responses to antibiotics have a similar protective role in Chapter 2. Indeed, we found that the trimethoprim-induced acid stress response protects bacteria from subsequent acid stress. We combined microfluidics with time-lapse imaging to monitor survival, intracellular pH, and acid stress response in single cells. This approach revealed that the variable expression of the acid resistance operon gadBC strongly correlates with single-cell survival time. Cells with higher gadBC expression following trimethoprim maintain higher intracellular pH and survive the acid stress longer. Overall, we provide a way to identify single-cell cross-protection between antibiotics and environmental stressors from temporal gene expression data, and show how antibiotics can increase bacterial fitness in changing environments. While gene expression changes to antibiotics show a clear temporal structure at the population-level, it is unclear whether this clear temporal order is followed by every single cell. Using dual-reporter strains described in Chapter 3, we measured gene expression dynamics of promoter pairs in the same cells using microfluidics and microscopy. Chapter 4 shows that the oxidative stress response and the DNA stress response showed little timing variability and a clear temporal order under the antibiotic nitrofurantoin. In contrast, the acid stress response under trimethoprim ran independently from all other activated response programs including the DNA stress response, which showed particularly high timing variability in this stress condition. In summary, this approach provides insight into the temporal organization of gene expression programs at the single-cell level and suggests dependencies between response programs and the underlying variability-introducing mechanisms. Altogether, this work advances our understanding of the diverse effects that antibiotics have on bacteria. These results were obtained by taking into account gene expression dynamics, which allowed us to identify general principles, molecular mechanisms, and dependencies between genes. Our findings may have implications for infectious disease treatments, and microbial communities in the human body and in nature.
AU - Mitosch, Karin
ID - 818
SN - 2663-337X
TI - Timing, variability and cross-protection in bacteria – insights from dynamic gene expression responses to antibiotics
ER -
TY - JOUR
AB - Background: Social insects form densely crowded societies in environments with high pathogen loads, but have evolved collective defences that mitigate the impact of disease. However, colony-founding queens lack this protection and suffer high rates of mortality. The impact of pathogens may be exacerbated in species where queens found colonies together, as healthy individuals may contract pathogens from infectious co-founders. Therefore, we tested whether ant queens avoid founding colonies with pathogen-exposed conspecifics and how they might limit disease transmission from infectious individuals. Results: Using Lasius Niger queens and a naturally infecting fungal pathogen Metarhizium brunneum, we observed that queens were equally likely to found colonies with another pathogen-exposed or sham-treated queen. However, when one queen died, the surviving individual performed biting, burial and removal of the corpse. These undertaking behaviours were performed prophylactically, i.e. targeted equally towards non-infected and infected corpses, as well as carried out before infected corpses became infectious. Biting and burial reduced the risk of the queens contracting and dying from disease from an infectious corpse of a dead co-foundress. Conclusions: We show that co-founding ant queens express undertaking behaviours that, in mature colonies, are performed exclusively by workers. Such infection avoidance behaviours act before the queens can contract the disease and will therefore improve the overall chance of colony founding success in ant queens.
AU - Pull, Christopher
AU - Cremer, Sylvia
ID - 732
IS - 1
JF - BMC Evolutionary Biology
SN - 14712148
TI - Co-founding ant queens prevent disease by performing prophylactic undertaking behaviour
VL - 17
ER -
TY - JOUR
AB - Antibiotics elicit drastic changes in microbial gene expression, including the induction of stress response genes. While certain stress responses are known to “cross-protect” bacteria from other stressors, it is unclear whether cellular responses to antibiotics have a similar protective role. By measuring the genome-wide transcriptional response dynamics of Escherichia coli to four antibiotics, we found that trimethoprim induces a rapid acid stress response that protects bacteria from subsequent exposure to acid. Combining microfluidics with time-lapse imaging to monitor survival and acid stress response in single cells revealed that the noisy expression of the acid resistance operon gadBC correlates with single-cell survival. Cells with higher gadBC expression following trimethoprim maintain higher intracellular pH and survive the acid stress longer. The seemingly random single-cell survival under acid stress can therefore be predicted from gadBC expression and rationalized in terms of GadB/C molecular function. Overall, we provide a roadmap for identifying the molecular mechanisms of single-cell cross-protection between antibiotics and other stressors.
AU - Mitosch, Karin
AU - Rieckh, Georg
AU - Bollenbach, Tobias
ID - 666
IS - 4
JF - Cell Systems
SN - 24054712
TI - Noisy response to antibiotic stress predicts subsequent single cell survival in an acidic environment
VL - 4
ER -
TY - JOUR
AB - Social insect societies are long-standing models for understanding social behaviour and evolution. Unlike other advanced biological societies (such as the multicellular body), the component parts of social insect societies can be easily deconstructed and manipulated. Recent methodological and theoretical innovations have exploited this trait to address an expanded range of biological questions. We illustrate the broadening range of biological insight coming from social insect biology with four examples. These new frontiers promote open-minded, interdisciplinary exploration of one of the richest and most complex of biological phenomena: sociality.
AU - Kennedy, Patrick
AU - Baron, Gemma
AU - Qiu, Bitao
AU - Freitak, Dalial
AU - Helantera, Heikki
AU - Hunt, Edmund
AU - Manfredini, Fabio
AU - O'Shea Wheller, Thomas
AU - Patalano, Solenn
AU - Pull, Christopher
AU - Sasaki, Takao
AU - Taylor, Daisy
AU - Wyatt, Christopher
AU - Sumner, Seirian
ID - 734
IS - 11
JF - Trends in Ecology and Evolution
SN - 01695347
TI - Deconstructing superorganisms and societies to address big questions in biology
VL - 32
ER -
TY - THES
AB - This dissertation focuses on algorithmic aspects of program verification, and presents modeling and complexity advances on several problems related to the
static analysis of programs, the stateless model checking of concurrent programs, and the competitive analysis of real-time scheduling algorithms.
Our contributions can be broadly grouped into five categories.
Our first contribution is a set of new algorithms and data structures for the quantitative and data-flow analysis of programs, based on the graph-theoretic notion of treewidth.
It has been observed that the control-flow graphs of typical programs have special structure, and are characterized as graphs of small treewidth.
We utilize this structural property to provide faster algorithms for the quantitative and data-flow analysis of recursive and concurrent programs.
In most cases we make an algebraic treatment of the considered problem,
where several interesting analyses, such as the reachability, shortest path, and certain kind of data-flow analysis problems follow as special cases.
We exploit the constant-treewidth property to obtain algorithmic improvements for on-demand versions of the problems,
and provide data structures with various tradeoffs between the resources spent in the preprocessing and querying phase.
We also improve on the algorithmic complexity of quantitative problems outside the algebraic path framework,
namely of the minimum mean-payoff, minimum ratio, and minimum initial credit for energy problems.
Our second contribution is a set of algorithms for Dyck reachability with applications to data-dependence analysis and alias analysis.
In particular, we develop an optimal algorithm for Dyck reachability on bidirected graphs, which are ubiquitous in context-insensitive, field-sensitive points-to analysis.
Additionally, we develop an efficient algorithm for context-sensitive data-dependence analysis via Dyck reachability,
where the task is to obtain analysis summaries of library code in the presence of callbacks.
Our algorithm preprocesses libraries in almost linear time, after which the contribution of the library in the complexity of the client analysis is (i)~linear in the number of call sites and (ii)~only logarithmic in the size of the whole library, as opposed to linear in the size of the whole library.
Finally, we prove that Dyck reachability is Boolean Matrix Multiplication-hard in general, and the hardness also holds for graphs of constant treewidth.
This hardness result strongly indicates that there exist no combinatorial algorithms for Dyck reachability with truly subcubic complexity.
Our third contribution is the formalization and algorithmic treatment of the Quantitative Interprocedural Analysis framework.
In this framework, the transitions of a recursive program are annotated as good, bad or neutral, and receive a weight which measures
the magnitude of their respective effect.
The Quantitative Interprocedural Analysis problem asks to determine whether there exists an infinite run of the program where the long-run ratio of the bad weights over the good weights is above a given threshold.
We illustrate how several quantitative problems related to static analysis of recursive programs can be instantiated in this framework,
and present some case studies to this direction.
Our fourth contribution is a new dynamic partial-order reduction for the stateless model checking of concurrent programs. Traditional approaches rely on the standard Mazurkiewicz equivalence between traces, by means of partitioning the trace space into equivalence classes, and attempting to explore a few representatives from each class.
We present a new dynamic partial-order reduction method called the Data-centric Partial Order Reduction (DC-DPOR).
Our algorithm is based on a new equivalence between traces, called the observation equivalence.
DC-DPOR explores a coarser partitioning of the trace space than any exploration method based on the standard Mazurkiewicz equivalence.
Depending on the program, the new partitioning can be even exponentially coarser.
Additionally, DC-DPOR spends only polynomial time in each explored class.
Our fifth contribution is the use of automata and game-theoretic verification techniques in the competitive analysis and synthesis of real-time scheduling algorithms for firm-deadline tasks.
On the analysis side, we leverage automata on infinite words to compute the competitive ratio of real-time schedulers subject to various environmental constraints.
On the synthesis side, we introduce a new instance of two-player mean-payoff partial-information games, and show
how the synthesis of an optimal real-time scheduler can be reduced to computing winning strategies in this new type of games.
AU - Pavlogiannis, Andreas
ID - 821
SN - 2663-337X
TI - Algorithmic advances in program analysis and their applications
ER -
TY - THES
AB - The lac operon is a classic model system for bacterial gene regulation, and has been studied extensively in E. coli, a classic model organism. However, not much is known about E. coli’s ecology and life outside the laboratory, in particular in soil and water environments. The natural diversity of the lac operon outside the laboratory, its role in the ecology of E. coli and the selection pressures it is exposed to, are similarly unknown.
In Chapter Two of this thesis, I explore the genetic diversity, phylogenetic history and signatures of selection of the lac operon across 20 natural isolates of E. coli and divergent clades of Escherichia. I found that complete lac operons were present in all isolates examined, which in all but one case were functional. The lac operon phylogeny conformed to the whole-genome phylogeny of the divergent Escherichia clades, which excludes horizontal gene transfer as an explanation for the presence of functional lac operons in these clades. All lac operon genes showed a signature of purifying selection; this signature was strongest for the lacY gene. Lac operon genes of human and environmental isolates showed similar signatures of selection, except the lacZ gene, which showed a stronger signature of selection in environmental isolates.
In Chapter Three, I try to identify the natural genetic variation relevant for phenotype and fitness in the lac operon, comparing growth rate on lactose and LacZ activity of the lac operons of these wild isolates in a common genetic background. Sequence variation in the lac promoter region, upstream of the -10 and -35 RNA polymerase binding motif, predicted variation in LacZ activity at full induction, using a thermodynamic model of polymerase binding (Tugrul, 2016). However, neither variation in LacZ activity, nor RNA polymerase binding predicted by the model correlated with variation in growth rate. Lac operons of human and environmental isolates did not differ systematically in either growth rate on lactose or LacZ protein activity, suggesting that these lac operons have been exposed to similar selection pressures. We thus have no evidence that the phenotypic variation we measured is relevant for fitness.
To start assessing the effect of genomic background on the growth phenotype conferred by the lac operon, I compared growth on minimal medium with lactose between lac operon constructs and the corresponding original isolates, I found that maximal growth rate was determined by genomic background, with almost all backgrounds conferring higher growth rates than lab strain K12 MG1655. However, I found no evidence that the lactose concentration at which growth was half maximal depended on genomic background.
AU - Jesse, Fabienne
ID - 820
SN - 2663-337X
TI - The lac operon in the wild
ER -
TY - THES
AB - This thesis describes a brittle fracture simulation method for visual effects applications. Building upon a symmetric Galerkin boundary element method, we first compute stress intensity factors following the theory of linear elastic fracture mechanics. We then use these stress intensities to simulate the motion of a propagating crack front at a significantly higher resolution than the overall deformation of the breaking object. Allowing for spatial variations of the material's toughness during crack propagation produces visually realistic, highly-detailed fracture surfaces. Furthermore, we introduce approximations for stress intensities and crack opening displacements, resulting in both practical speed-up and theoretically superior runtime complexity compared to previous methods. While we choose a quasi-static approach to fracture mechanics, ignoring dynamic deformations, we also couple our fracture simulation framework to a standard rigid-body dynamics solver, enabling visual effects artists to simulate both large scale motion, as well as fracturing due to collision forces in a combined system. As fractures inside of an object grow, their geometry must be represented both in the coarse boundary element mesh, as well as at the desired fine output resolution. Using a boundary element method, we avoid complicated volumetric meshing operations. Instead we describe a simple set of surface meshing operations that allow us to progressively add cracks to the mesh of an object and still re-use all previously computed entries of the linear boundary element system matrix. On the high resolution level, we opt for an implicit surface representation. We then describe how to capture fracture surfaces during crack propagation, as well as separate the individual fragments resulting from the fracture process, based on this implicit representation. We show results obtained with our method, either solving the full boundary element system in every time step, or alternatively using our fast approximations. These results demonstrate that both of these methods perform well in basic test cases and produce realistic fracture surfaces. Furthermore we show that our fast approximations substantially out-perform the standard approach in more demanding scenarios. Finally, these two methods naturally combine, using the full solution while the problem size is manageably small and switching to the fast approximations later on. The resulting hybrid method gives the user a direct way to choose between speed and accuracy of the simulation.
AU - Hahn, David
ID - 839
SN - 2663-337X
TI - Brittle fracture simulation with boundary elements for computer graphics
ER -
TY - THES
AB - In this thesis we discuss the exact security of message authentications codes HMAC , NMAC , and PMAC . NMAC is a mode of operation which turns a fixed input-length keyed hash function f into a variable input-length function. A practical single-key variant of NMAC called HMAC is a very popular and widely deployed message authentication code (MAC). PMAC is a block-cipher based mode of operation, which also happens to be the most famous fully parallel MAC. NMAC was introduced by Bellare, Canetti and Krawczyk Crypto’96, who proved it to be a secure pseudorandom function (PRF), and thus also a MAC, under two assumptions. Unfortunately, for many instantiations of HMAC one of them has been found to be wrong. To restore the provable guarantees for NMAC , Bellare [Crypto’06] showed its security without this assumption. PMAC was introduced by Black and Rogaway at Eurocrypt 2002. If instantiated with a pseudorandom permutation over n -bit strings, PMAC constitutes a provably secure variable input-length PRF. For adversaries making q queries, each of length at most ` (in n -bit blocks), and of total length σ ≤ q` , the original paper proves an upper bound on the distinguishing advantage of O ( σ 2 / 2 n ), while the currently best bound is O ( qσ/ 2 n ). In this work we show that this bound is tight by giving an attack with advantage Ω( q 2 `/ 2 n ). In the PMAC construction one initially XORs a mask to every message block, where the mask for the i th block is computed as τ i := γ i · L , where L is a (secret) random value, and γ i is the i -th codeword of the Gray code. Our attack applies more generally to any sequence of γ i ’s which contains a large coset of a subgroup of GF (2 n ). As for NMAC , our first contribution is a simpler and uniform proof: If f is an ε -secure PRF (against q queries) and a δ - non-adaptively secure PRF (against q queries), then NMAC f is an ( ε + `qδ )-secure PRF against q queries of length at most ` blocks each. We also show that this ε + `qδ bound is basically tight by constructing an f for which an attack with advantage `qδ exists. Moreover, we analyze the PRF-security of a modification of NMAC called NI by An and Bellare that avoids the constant rekeying on multi-block messages in NMAC and allows for an information-theoretic analysis. We carry out such an analysis, obtaining a tight `q 2 / 2 c bound for this step, improving over the trivial bound of ` 2 q 2 / 2 c . Finally, we investigate, if the security of PMAC can be further improved by using τ i ’s that are k -wise independent, for k > 1 (the original has k = 1). We observe that the security of PMAC will not increase in general if k = 2, and then prove that the security increases to O ( q 2 / 2 n ), if the k = 4. Due to simple extension attacks, this is the best bound one can hope for, using any distribution on the masks. Whether k = 3 is already sufficient to get this level of security is left as an open problem. Keywords: Message authentication codes, Pseudorandom functions, HMAC, PMAC.
AU - Rybar, Michal
ID - 838
SN - 2663-337X
TI - (The exact security of) Message authentication codes
ER -
TY - JOUR
AB - PMAC is a simple and parallel block-cipher mode of operation, which was introduced by Black and Rogaway at Eurocrypt 2002. If instantiated with a (pseudo)random permutation over n-bit strings, PMAC constitutes a provably secure variable input-length (pseudo)random function. For adversaries making q queries, each of length at most l (in n-bit blocks), and of total length σ ≤ ql, the original paper proves an upper bound on the distinguishing advantage of Ο(σ2/2n), while the currently best bound is Ο (qσ/2n).In this work we show that this bound is tight by giving an attack with advantage Ω (q2l/2n). In the PMAC construction one initially XORs a mask to every message block, where the mask for the ith block is computed as τi := γi·L, where L is a (secret) random value, and γi is the i-th codeword of the Gray code. Our attack applies more generally to any sequence of γi’s which contains a large coset of a subgroup of GF(2n). We then investigate if the security of PMAC can be further improved by using τi’s that are k-wise independent, for k > 1 (the original distribution is only 1-wise independent). We observe that the security of PMAC will not increase in general, even if the masks are chosen from a 2-wise independent distribution, and then prove that the security increases to O(q<2/2n), if the τi are 4-wise independent. Due to simple extension attacks, this is the best bound one can hope for, using any distribution on the masks. Whether 3-wise independence is already sufficient to get this level of security is left as an open problem.
AU - Gazi, Peter
AU - Pietrzak, Krzysztof Z
AU - Rybar, Michal
ID - 6196
IS - 2
JF - IACR Transactions on Symmetric Cryptology
TI - The exact security of PMAC
VL - 2016
ER -
TY - THES
AB - Cell-cell contact formation constitutes the first step in the emergence of multicellularity in evolution, thereby allowing the differentiation of specialized cell types. In metazoan development, cell-cell contact formation is thought to influence cell fate specification, and cell fate specification has been implicated in cell-cell contact formation. However, remarkably little is yet known about whether and how the interaction and feedback between cell-cell contact formation and cell fate specification affect development. Here we identify a positive feedback loop between cell-cell contact duration, morphogen signaling and mesendoderm cell fate specification during zebrafish gastrulation. We show that long lasting cell-cell contacts enhance the competence of prechordal plate (ppl) progenitor cells to respond to Nodal signaling, required for proper ppl cell fate specification. We further show that Nodal signalling romotes ppl cell-cell contact duration, thereby generating an effective positive feedback loop between ppl cell-cell contact duration and cell fate specification. Finally, by using a combination of theoretical modeling and experimentation, we show that this feedback loop determines whether anterior axial mesendoderm cells become ppl progenitors or, instead, turn into endoderm progenitors. Our findings reveal that the gene regulatory networks leading to cell fate diversification within the developing embryo are controlled by the interdependent activities of cell-cell signaling and contact formation.
AU - Barone, Vanessa
ID - 961
SN - 2663-337X
TI - Cell adhesion and cell fate: An effective feedback loop during zebrafish gastrulation
ER -
TY - THES
AB - The hippocampus is a key brain region for memory and notably for spatial memory, and is needed for both spatial working and reference memories. Hippocampal place cells selectively discharge in specific locations of the environment to form mnemonic represen tations of space. Several behavioral protocols have been designed to test spatial memory which requires the experimental subject to utilize working memory and reference memory. However, less is known about how these memory traces are presented in the hippo campus, especially considering tasks that require both spatial working and long -term reference memory demand. The aim of my thesis was to elucidate how spatial working memory, reference memory, and the combination of both are represented in the hippocampus. In this thesis, using a radial eight -arm maze, I examined how the combined demand on these memories influenced place cell assemblies while reference memories were partially updated by changing some of the reward- arms. This was contrasted with task varian ts requiring working or reference memories only. Reference memory update led to gradual place field shifts towards the rewards on the switched arms. Cells developed enhanced firing in passes between newly -rewarded arms as compared to those containing an unchanged reward. The working memory task did not show such gradual changes. Place assemblies on occasions replayed trajectories of the maze; at decision points the next arm choice was preferentially replayed in tasks needing reference memory while in the pure working memory task the previously visited arm was replayed. Hence trajectory replay only reflected the decision of the animal in tasks needing reference memory update. At the reward locations, in all three tasks outbound trajectories of the current arm were preferentially replayed, showing the animals’ next path to the center. At reward locations trajectories were replayed preferentially in reverse temporal order. Moreover, in the center reverse replay was seen in the working memory task but in the other tasks forward replay was seen. Hence, the direction of reactivation was determined by the goal locations so that part of the trajectory which was closer to the goal was reactivated later in an HSE while places further away from the goal were reactivated earlier. Altogether my work demonstrated that reference memory update triggers several levels of reorganization of the hippocampal cognitive map which are not seen in simpler working memory demand s. Moreover, hippocampus is likely to be involved in spatial decisions through reactivating planned trajectories when reference memory recall is required for such a decision.
AU - Xu, Haibing
ID - 837
SN - 2663-337X
TI - Reactivation of the hippocampal cognitive map in goal-directed spatial tasks
ER -
TY - THES
AB - The thesis encompasses several topics of plant cell biology which were studied in the model plant Arabidopsis thaliana. Chapter 1 concerns the plant hormone auxin and its polar transport through cells and tissues. The highly controlled, directional transport of auxin is facilitated by plasma membrane-localized transporters. Transporters from the PIN family direct auxin transport due to their polarized localizations at cell membranes. Substantial effort has been put into research on cellular trafficking of PIN proteins, which is thought to underlie their polar distribution. I participated in a forward genetic screen aimed at identifying novel regulators of PIN polarity. The screen yielded several genes which may be involved in PIN polarity regulation or participate in polar auxin transport by other means. Chapter 2 focuses on the endomembrane system, with particular attention to clathrin-mediated endocytosis. The project started with identification of several proteins that interact with clathrin light chains. Among them, I focused on two putative homologues of auxilin, which in non-plant systems is an endocytotic factor known for uncoating clathrin-coated vesicles in the final step of endocytosis. The body of my work consisted of an in-depth characterization of transgenic A. thaliana lines overexpressing these putative auxilins in an inducible manner. Overexpression of these proteins leads to an inhibition of endocytosis, as documented by imaging of cargoes and clathrin-related endocytic machinery. An extension of this work is an investigation into a concept of homeostatic regulation acting between distinct transport processes in the endomembrane system. With auxilin overexpressing lines, where endocytosis is blocked specifically, I made observations on the mutual relationship between two opposite trafficking processes of secretion and endocytosis. In Chapter 3, I analyze cortical microtubule arrays and their relationship to auxin signaling and polarized growth in elongating cells. In plants, microtubules are organized into arrays just below the plasma membrane, and it is thought that their function is to guide membrane-docked cellulose synthase complexes. These, in turn, influence cell wall structure and cell shape by directed deposition of cellulose fibres. In elongating cells, cortical microtubule arrays are able to reorient in relation to long cell axis, and these reorientations have been linked to cell growth and to signaling of growth-regulating factors such as auxin or light. In this chapter, I am addressing the causal relationship between microtubule array reorientation, growth, and auxin signaling. I arrive at a model where array reorientation is not guided by auxin directly, but instead is only controlled by growth, which, in turn, is regulated by auxin.
AU - Adamowski, Maciek
ID - 938
SN - 2663-337X
TI - Investigations into cell polarity and trafficking in the plant model Arabidopsis thaliana
ER -
TY - THES
AB - An instance of the Constraint Satisfaction Problem (CSP) is given by a finite set of
variables, a finite domain of labels, and a set of constraints, each constraint acting on
a subset of the variables. The goal is to find an assignment of labels to its variables
that satisfies all constraints (or decide whether one exists). If we allow more general
“soft” constraints, which come with (possibly infinite) costs of particular assignments,
we obtain instances from a richer class called Valued Constraint Satisfaction Problem
(VCSP). There the goal is to find an assignment with minimum total cost.
In this thesis, we focus (assuming that P
6
=
NP) on classifying computational com-
plexity of CSPs and VCSPs under certain restricting conditions. Two results are the core
content of the work. In one of them, we consider VCSPs parametrized by a constraint
language, that is the set of “soft” constraints allowed to form the instances, and finish
the complexity classification modulo (missing pieces of) complexity classification for
analogously parametrized CSP. The other result is a generalization of Edmonds’ perfect
matching algorithm. This generalization contributes to complexity classfications in two
ways. First, it gives a new (largest known) polynomial-time solvable class of Boolean
CSPs in which every variable may appear in at most two constraints and second, it
settles full classification of Boolean CSPs with planar drawing (again parametrized by a
constraint language).
AU - Rolinek, Michal
ID - 992
SN - 2663-337X
TI - Complexity of constraint satisfaction
ER -
TY - JOUR
AB - Mapping every simplex in the Delaunay mosaic of a discrete point set to the radius of the smallest empty circumsphere gives a generalized discrete Morse function. Choosing the points from a Poisson point process in ℝ n , we study the expected number of simplices in the Delaunay mosaic as well as the expected number of critical simplices and nonsingular intervals in the corresponding generalized discrete gradient. Observing connections with other probabilistic models, we obtain precise expressions for the expected numbers in low dimensions. In particular, we obtain the expected numbers of simplices in the Poisson–Delaunay mosaic in dimensions n ≤ 4.
AU - Edelsbrunner, Herbert
AU - Nikitenko, Anton
AU - Reitzner, Matthias
ID - 718
IS - 3
JF - Advances in Applied Probability
SN - 00018678
TI - Expected sizes of poisson Delaunay mosaics and their discrete Morse functions
VL - 49
ER -
TY - JOUR
AB - Synaptotagmin 7 (Syt7) is thought to be a Ca2+ sensor that mediates asynchronous transmitter release and facilitation at synapses. However, Syt7 is strongly expressed in fast-spiking, parvalbumin-expressing GABAergic interneurons, and the output synapses of these neurons produce only minimal asynchronous release and show depression rather than facilitation. To resolve this apparent contradiction, we examined the effects of genetic elimination of Syt7 on synaptic transmission at the GABAergic basket cell (BC)-Purkinje cell (PC) synapse in cerebellum. Our results indicate that at the BC-PC synapse, Syt7 contributes to asynchronous release, pool replenishment, and facilitation. In combination, these three effects ensure efficient transmitter release during high-frequency activity and guarantee frequency independence of inhibition. Our results identify a distinct function of Syt7: ensuring the efficiency of high-frequency inhibitory synaptic transmission
AU - Chen, Chong
AU - Satterfield, Rachel
AU - Young, Samuel
AU - Jonas, Peter M
ID - 749
IS - 8
JF - Cell Reports
SN - 22111247
TI - Triple function of Synaptotagmin 7 ensures efficiency of high-frequency transmission at central GABAergic synapses
VL - 21
ER -
TY - CONF
AB - Proofs of space (PoS) were suggested as more ecological and economical alternative to proofs of work, which are currently used in blockchain designs like Bitcoin. The existing PoS are based on rather sophisticated graph pebbling lower bounds. Much simpler and in several aspects more efficient schemes based on inverting random functions have been suggested, but they don’t give meaningful security guarantees due to existing time-memory trade-offs. In particular, Hellman showed that any permutation over a domain of size N can be inverted in time T by an algorithm that is given S bits of auxiliary information whenever (Formula presented). For functions Hellman gives a weaker attack with S2· T≈ N2 (e.g., S= T≈ N2/3). To prove lower bounds, one considers an adversary who has access to an oracle f: [ N] → [N] and can make T oracle queries. The best known lower bound is S· T∈ Ω(N) and holds for random functions and permutations. We construct functions that provably require more time and/or space to invert. Specifically, for any constant k we construct a function [N] → [N] that cannot be inverted unless Sk· T∈ Ω(Nk) (in particular, S= T≈ (Formula presented). Our construction does not contradict Hellman’s time-memory trade-off, because it cannot be efficiently evaluated in forward direction. However, its entire function table can be computed in time quasilinear in N, which is sufficient for the PoS application. Our simplest construction is built from a random function oracle g: [N] × [N] → [ N] and a random permutation oracle f: [N] → N] and is defined as h(x) = g(x, x′) where f(x) = π(f(x′)) with π being any involution without a fixed point, e.g. flipping all the bits. For this function we prove that any adversary who gets S bits of auxiliary information, makes at most T oracle queries, and inverts h on an ϵ fraction of outputs must satisfy S2· T∈ Ω(ϵ2N2).
AU - Abusalah, Hamza M
AU - Alwen, Joel F
AU - Cohen, Bram
AU - Khilko, Danylo
AU - Pietrzak, Krzysztof Z
AU - Reyzin, Leonid
ID - 559
SN - 978-331970696-2
TI - Beyond Hellman’s time-memory trade-offs with applications to proofs of space
VL - 10625
ER -
TY - JOUR
AB - We prove that a system of N fermions interacting with an additional particle via point interactions is stable if the ratio of the mass of the additional particle to the one of the fermions is larger than some critical m*. The value of m* is independent of N and turns out to be less than 1. This fact has important implications for the stability of the unitary Fermi gas. We also characterize the domain of the Hamiltonian of this model, and establish the validity of the Tan relations for all wave functions in the domain.
AU - Moser, Thomas
AU - Seiringer, Robert
ID - 741
IS - 1
JF - Communications in Mathematical Physics
SN - 00103616
TI - Stability of a fermionic N+1 particle system with point interactions
VL - 356
ER -
TY - JOUR
AB - For large random matrices X with independent, centered entries but not necessarily identical variances, the eigenvalue density of XX* is well-approximated by a deterministic measure on ℝ. We show that the density of this measure has only square and cubic-root singularities away from zero. We also extend the bulk local law in [5] to the vicinity of these singularities.
AU - Alt, Johannes
ID - 550
JF - Electronic Communications in Probability
SN - 1083589X
TI - Singularities of the density of states of random Gram matrices
VL - 22
ER -
TY - CONF
AB - Despite researchers’ efforts in the last couple of decades, reachability analysis is still a challenging problem even for linear hybrid systems. Among the existing approaches, the most practical ones are mainly based on bounded-time reachable set over-approximations. For the purpose of unbounded-time analysis, one important strategy is to abstract the original system and find an invariant for the abstraction. In this paper, we propose an approach to constructing a new kind of abstraction called conic abstraction for affine hybrid systems, and to computing reachable sets based on this abstraction. The essential feature of a conic abstraction is that it partitions the state space of a system into a set of convex polyhedral cones which is derived from a uniform conic partition of the derivative space. Such a set of polyhedral cones is able to cut all trajectories of the system into almost straight segments so that every segment of a reach pipe in a polyhedral cone tends to be straight as well, and hence can be over-approximated tightly by polyhedra using similar techniques as HyTech or PHAVer. In particular, for diagonalizable affine systems, our approach can guarantee to find an invariant for unbounded reachable sets, which is beyond the capability of bounded-time reachability analysis tools. We implemented the approach in a tool and experiments on benchmarks show that our approach is more powerful than SpaceEx and PHAVer in dealing with diagonalizable systems.
AU - Bogomolov, Sergiy
AU - Giacobbe, Mirco
AU - Henzinger, Thomas A
AU - Kong, Hui
ID - 647
SN - 978-331965764-6
TI - Conic abstractions for hybrid systems
VL - 10419
ER -
TY - CONF
AB - Template polyhedra generalize intervals and octagons to polyhedra whose facets are orthogonal to a given set of arbitrary directions. They have been employed in the abstract interpretation of programs and, with particular success, in the reachability analysis of hybrid automata. While previously, the choice of directions has been left to the user or a heuristic, we present a method for the automatic discovery of directions that generalize and eliminate spurious counterexamples. We show that for the class of convex hybrid automata, i.e., hybrid automata with (possibly nonlinear) convex constraints on derivatives, such directions always exist and can be found using convex optimization. We embed our method inside a CEGAR loop, thus enabling the time-unbounded reachability analysis of an important and richer class of hybrid automata than was previously possible. We evaluate our method on several benchmarks, demonstrating also its superior efficiency for the special case of linear hybrid automata.
AU - Bogomolov, Sergiy
AU - Frehse, Goran
AU - Giacobbe, Mirco
AU - Henzinger, Thomas A
ID - 631
SN - 978-366254576-8
TI - Counterexample guided refinement of template polyhedra
VL - 10205
ER -
TY - JOUR
AB - We show that matrix elements of functions of N × N Wigner matrices fluctuate on a scale of order N−1/2 and we identify the limiting fluctuation. Our result holds for any function f of the matrix that has bounded variation thus considerably relaxing the regularity requirement imposed in [7, 11].
AU - Erdös, László
AU - Schröder, Dominik J
ID - 1144
JF - Electronic Communications in Probability
TI - Fluctuations of functions of Wigner matrices
VL - 21
ER -
TY - JOUR
AB - Color texture reproduction in 3D printing commonly ignores volumetric light transport (cross-talk) between surface points on a 3D print. Such light diffusion leads to significant blur of details and color bleeding, and is particularly severe for highly translucent resin-based print materials. Given their widely varying scattering properties, this cross-talk between surface points strongly depends on the internal structure of the volume surrounding each surface point. Existing scattering-aware methods use simplified models for light diffusion, and often accept the visual blur as an immutable property of the print medium. In contrast, our work counteracts heterogeneous scattering to obtain the impression of a crisp albedo texture on top of the 3D print, by optimizing for a fully volumetric material distribution that preserves the target appearance. Our method employs an efficient numerical optimizer on top of a general Monte-Carlo simulation of heterogeneous scattering, supported by a practical calibration procedure to obtain scattering parameters from a given set of printer materials. Despite the inherent translucency of the medium, we reproduce detailed surface textures on 3D prints. We evaluate our system using a commercial, five-tone 3D print process and compare against the printer’s native color texturing mode, demonstrating that our method preserves high-frequency features well without having to compromise on color gamut.
AU - Elek, Oskar
AU - Sumin, Denis
AU - Zhang, Ran
AU - Weyrich, Tim
AU - Myszkowski, Karol
AU - Bickel, Bernd
AU - Wilkie, Alexander
AU - Krivanek, Jaroslav
ID - 486
IS - 6
JF - ACM Transactions on Graphics
SN - 07300301
TI - Scattering-aware texture reproduction for 3D printing
VL - 36
ER -
TY - CONF
AB - We develop a probabilistic technique for colorizing grayscale natural images. In light of the intrinsic uncertainty of this task, the proposed probabilistic framework has numerous desirable properties. In particular, our model is able to produce multiple plausible and vivid colorizations for a given grayscale image and is one of the first colorization models to provide a proper stochastic sampling scheme. Moreover, our training procedure is supported by a rigorous theoretical framework that does not require any ad hoc heuristics and allows for efficient modeling and learning of the joint pixel color distribution.We demonstrate strong quantitative and qualitative experimental results on the CIFAR-10 dataset and the challenging ILSVRC 2012 dataset.
AU - Royer, Amélie
AU - Kolesnikov, Alexander
AU - Lampert, Christoph
ID - 911
TI - Probabilistic image colorization
ER -
TY - CONF
AB - For many cryptographic primitives, it is relatively easy to achieve selective security (where the adversary commits a-priori to some of the choices to be made later in the attack) but appears difficult to achieve the more natural notion of adaptive security (where the adversary can make all choices on the go as the attack progresses). A series of several recent works shows how to cleverly achieve adaptive security in several such scenarios including generalized selective decryption (Panjwani, TCC ’07 and Fuchsbauer et al., CRYPTO ’15), constrained PRFs (Fuchsbauer et al., ASIACRYPT ’14), and Yao garbled circuits (Jafargholi and Wichs, TCC ’16b). Although the above works expressed vague intuition that they share a common technique, the connection was never made precise. In this work we present a new framework that connects all of these works and allows us to present them in a unified and simplified fashion. Moreover, we use the framework to derive a new result for adaptively secure secret sharing over access structures defined via monotone circuits. We envision that further applications will follow in the future. Underlying our framework is the following simple idea. It is well known that selective security, where the adversary commits to n-bits of information about his future choices, automatically implies adaptive security at the cost of amplifying the adversary’s advantage by a factor of up to 2n. However, in some cases the proof of selective security proceeds via a sequence of hybrids, where each pair of adjacent hybrids locally only requires some smaller partial information consisting of m ≪ n bits. The partial information needed might be completely different between different pairs of hybrids, and if we look across all the hybrids we might rely on the entire n-bit commitment. Nevertheless, the above is sufficient to prove adaptive security, at the cost of amplifying the adversary’s advantage by a factor of only 2m ≪ 2n. In all of our examples using the above framework, the different hybrids are captured by some sort of a graph pebbling game and the amount of information that the adversary needs to commit to in each pair of hybrids is bounded by the maximum number of pebbles in play at any point in time. Therefore, coming up with better strategies for proving adaptive security translates to various pebbling strategies for different types of graphs.
AU - Jafargholi, Zahra
AU - Kamath Hosdurg, Chethan
AU - Klein, Karen
AU - Komargodski, Ilan
AU - Pietrzak, Krzysztof Z
AU - Wichs, Daniel
ED - Katz, Jonathan
ED - Shacham, Hovav
ID - 637
SN - 978-331963687-0
TI - Be adaptive avoid overcommitting
VL - 10401
ER -
TY - GEN
AB - Mathematica notebooks used to generate figures.
AU - Etheridge, Alison
AU - Barton, Nicholas H
ID - 9842
TI - Data for: Establishment in a new habitat by polygenic adaptation
ER -
TY - CONF
AB - Greedy optimization methods such as Matching Pursuit (MP) and Frank-Wolfe (FW) algorithms regained popularity in recent years due to their simplicity, effectiveness and theoretical guarantees. MP and FW address optimization over the linear span and the convex hull of a set of atoms, respectively. In this paper, we consider the intermediate case of optimization over the convex cone, parametrized as the conic hull of a generic atom set, leading to the first principled definitions of non-negative MP algorithms for which we give explicit convergence rates and demonstrate excellent empirical performance. In particular, we derive sublinear (O(1/t)) convergence on general smooth and convex objectives, and linear convergence (O(e−t)) on strongly convex objectives, in both cases for general sets of atoms. Furthermore, we establish a clear correspondence of our algorithms to known algorithms from the MP and FW literature. Our novel algorithms and analyses target general atom sets and general objective functions, and hence are directly applicable to a large variety of learning settings.
AU - Locatello, Francesco
AU - Tschannen, Michael
AU - Rätsch, Gunnar
AU - Jaggi, Martin
ID - 14206
SN - 9781510860964
T2 - Advances in Neural Information Processing Systems
TI - Greedy algorithms for cone constrained optimization with convergence guarantees
ER -
TY - CONF
AB - Two of the most fundamental prototypes of greedy optimization are the matching pursuit and Frank-Wolfe algorithms. In this paper, we take a unified view on both classes of methods, leading to the first explicit convergence rates of matching pursuit methods in an optimization sense, for general sets of atoms. We derive sublinear (1/t) convergence for both classes on general smooth objectives, and linear convergence on strongly convex objectives, as well as a clear correspondence of algorithm variants. Our presented algorithms and rates are affine invariant, and do not need any incoherence or sparsity assumptions.
AU - Locatello, Francesco
AU - Khanna, Rajiv
AU - Tschannen, Michael
AU - Jaggi, Martin
ID - 14205
T2 - Proceedings of the 20th International Conference on Artificial Intelligence and Statistics
TI - A unified optimization view on generalized matching pursuit and Frank-Wolfe
VL - 54
ER -
TY - THES
AB - Restriction-modification (RM) represents the simplest and possibly the most widespread mechanism of self/non-self discrimination in nature. In order to provide bacteria with immunity against bacteriophages and other parasitic genetic elements, RM systems rely on a balance between two enzymes: the restriction enzyme, which cleaves non-self DNA at specific restriction sites, and the modification enzyme, which tags the host’s DNA as self and thus protects it from cleavage. In this thesis, I use population and single-cell level experiments in combination with mathematical modeling to study different aspects of the interplay between RM systems, bacteria and bacteriophages. First, I analyze how mutations in phage restriction sites affect the probability of phage escape – an inherently stochastic process, during which phages accidently get modified instead of restricted. Next, I use single-cell experiments to show that RM systems can, with a low probability, attack the genome of their bacterial host and that this primitive form of autoimmunity leads to a tradeoff between the evolutionary cost and benefit of RM systems. Finally, I investigate the nature of interactions between bacteria, RM systems and temperate bacteriophages to find that, as a consequence of phage escape and its impact on population dynamics, RM systems can promote acquisition of symbiotic bacteriophages, rather than limit it. The results presented here uncover new fundamental biological properties of RM systems and highlight their importance in the ecology and evolution of bacteria, bacteriophages and their interactions.
AU - Pleska, Maros
ID - 202
SN - 2663-337X
TI - Biology of restriction-modification systems at the single-cell and population level
ER -
TY - THES
AB - The main objects considered in the present work are simplicial and CW-complexes with vertices forming a random point cloud. In particular, we consider a Poisson point process in R^n and study Delaunay and Voronoi complexes of the first and higher orders and weighted Delaunay complexes obtained as sections of Delaunay complexes, as well as the Čech complex. Further, we examine theDelaunay complex of a Poisson point process on the sphere S^n, as well as of a uniform point cloud, which is equivalent to the convex hull, providing a connection to the theory of random polytopes. Each of the complexes in question can be endowed with a radius function, which maps its cells to the radii of appropriately chosen circumspheres, called the radius of the cell. Applying and developing discrete Morse theory for these functions, joining it together with probabilistic and sometimes analytic machinery, and developing several integral geometric tools, we aim at getting the distributions of circumradii of typical cells. For all considered complexes, we are able to generalize and obtain up to constants the distribution of radii of typical intervals of all types. In low dimensions the constants can be computed explicitly, thus providing the explicit expressions for the expected numbers of cells. In particular, it allows to find the expected density of simplices of every dimension for a Poisson point process in R^4, whereas the result for R^3 was known already in 1970's.
AU - Nikitenko, Anton
ID - 6287
SN - 2663-337X
TI - Discrete Morse theory for random complexes
ER -
TY - THES
AB - Contagious diseases must transmit from infectious to susceptible hosts in order to reproduce. Whilst vectored pathogens can rely on intermediaries to find new hosts for them, many infectious pathogens require close contact or direct interaction between hosts for transmission. Hence, this means that conspecifics are often the main source of infection for most animals and so, in theory, animals should avoid conspecifics to reduce their risk of infection. Of course, in reality animals must interact with one another, as a bare minimum, to mate. However, being social provides many additional benefits and group living has become a taxonomically diverse and widespread trait. How then do social animals overcome the issue of increased disease? Over the last few decades, the social insects (ants, termites and some bees and wasps) have become a model system for studying disease in social animals. On paper, a social insect colony should be particularly susceptible to disease, given that they often contain thousands of potential hosts that are closely related and frequently interact, as well as exhibiting stable environmental conditions that encourage microbial growth. Yet, disease outbreaks appear to be rare and attempts to eradicate pest species using pathogens have failed time and again. Evolutionary biologists investigating this observation have discovered that the reduced disease susceptibility in social insects is, in part, due to collectively performed disease defences of the workers. These defences act like a “social immune system” for the colony, resulting in a per capita decrease in disease, termed social immunity. Our understanding of social immunity, and its importance in relation to the immunological defences of each insect, continues to grow, but there remain many open questions. In this thesis I have studied disease defence in garden ants. In the first data chapter, I use the invasive garden ant, Lasius neglectus, to investigate how colonies mitigate lethal infections and prevent them from spreading systemically. I find that ants have evolved ‘destructive disinfection’ – a behaviour that uses endogenously produced acidic poison to kill diseased brood and to prevent the pathogen from replicating. In the second experimental chapter, I continue to study the use of poison in invasive garden ant colonies, finding that it is sprayed prophylactically within the nest. However, this spraying has negative effects on developing pupae when they have had their cocoons artificially removed. Hence, I suggest that acidic nest sanitation may be maintaining larval cocoon spinning in this species. In the next experimental chapter, I investigated how colony founding black garden ant queens (Lasius niger) prevent disease when a co-foundress dies. I show that ant queens prophylactically perform undertaking behaviours, similar to those performed by the workers in mature nests. When a co-foundress was infected, these undertaking behaviours improved the survival of the healthy queen. In the final data chapter, I explored how immunocompetence (measured as antifungal activity) changes as incipient black garden ant colonies grow and mature, from the solitary queen phase to colonies with several hundred workers. Queen and worker antifungal activity varied throughout this time period, but despite social immunity, did not decrease as colonies matured. In addition to the above data chapters, this thesis includes two co-authored reviews. In the first, we examine the state of the art in the field of social immunity and how it might develop in the future. In the second, we identify several challenges and open questions in the study of disease defence in animals. We highlight how social insects offer a unique model to tackle some of these problems, as disease defence can be studied from the cell to the society.
AU - Pull, Christopher
ID - 819
SN - 2663-337X
TI - Disease defence in garden ants
ER -