TY - JOUR
AB - Coordinated conformational transitions in oligomeric enzymatic complexes modulate function in response to substrates and play a crucial role in enzyme inhibition and activation. Caseinolytic protease (ClpP) is a tetradecameric complex, which has emerged as a drug target against multiple pathogenic bacteria. Activation of different ClpPs by inhibitors has been independently reported from drug development efforts, but no rationale for inhibitor-induced activation has been hitherto proposed. Using an integrated approach that includes x-ray crystallography, solid- and solution-state nuclear magnetic resonance, molecular dynamics simulations, and isothermal titration calorimetry, we show that the proteasome inhibitor bortezomib binds to the ClpP active-site serine, mimicking a peptide substrate, and induces a concerted allosteric activation of the complex. The bortezomib-activated conformation also exhibits a higher affinity for its cognate unfoldase ClpX. We propose a universal allosteric mechanism, where substrate binding to a single subunit locks ClpP into an active conformation optimized for chaperone association and protein processive degradation.
AU - Felix, Jan
AU - Weinhäupl, Katharina
AU - Chipot, Christophe
AU - Dehez, François
AU - Hessel, Audrey
AU - Gauto, Diego F.
AU - Morlot, Cecile
AU - Abian, Olga
AU - Gutsche, Irina
AU - Velazquez-Campoy, Adrian
AU - Schanda, Paul
AU - Fraga, Hugo
ID - 8406
IS - 9
JF - Science Advances
SN - 2375-2548
TI - Mechanism of the allosteric activation of the ClpP protease machinery by substrates and active-site inhibitors
VL - 5
ER -
TY - JOUR
AU - Schanda, Paul
ID - 8407
JF - Journal of Magnetic Resonance
KW - Nuclear and High Energy Physics
KW - Biophysics
KW - Biochemistry
KW - Condensed Matter Physics
SN - 1090-7807
TI - Relaxing with liquids and solids – A perspective on biomolecular dynamics
VL - 306
ER -
TY - JOUR
AB - Aromatic residues are located at structurally important sites of many proteins. Probing their interactions and dynamics can provide important functional insight but is challenging in large proteins. Here, we introduce approaches to characterize dynamics of phenylalanine residues using 1H-detected fast magic-angle spinning (MAS) NMR combined with a tailored isotope-labeling scheme. Our approach yields isolated two-spin systems that are ideally suited for artefact-free dynamics measurements, and allows probing motions effectively without molecular-weight limitations. The application to the TET2 enzyme assembly of ~0.5 MDa size, the currently largest protein assigned by MAS NMR, provides insights into motions occurring on a wide range of time scales (ps-ms). We quantitatively probe ring flip motions, and show the temperature dependence by MAS NMR measurements down to 100 K. Interestingly, favorable line widths are observed down to 100 K, with potential implications for DNP NMR. Furthermore, we report the first 13C R1ρ MAS NMR relaxation-dispersion measurements and detect structural excursions occurring on a microsecond time scale in the entry pore to the catalytic chamber and at a trimer interface that was proposed as exit pore. We show that the labeling scheme with deuteration at ca. 50 kHz MAS provides superior resolution compared to 100 kHz MAS experiments with protonated, uniformly 13C-labeled samples.
AU - Gauto, Diego F.
AU - Macek, Pavel
AU - Barducci, Alessandro
AU - Fraga, Hugo
AU - Hessel, Audrey
AU - Terauchi, Tsutomu
AU - Gajan, David
AU - Miyanoiri, Yohei
AU - Boisbouvier, Jerome
AU - Lichtenecker, Roman
AU - Kainosho, Masatsune
AU - Schanda, Paul
ID - 8408
IS - 28
JF - Journal of the American Chemical Society
KW - Colloid and Surface Chemistry
KW - Biochemistry
KW - General Chemistry
KW - Catalysis
SN - 0002-7863
TI - Aromatic ring dynamics, thermal activation, and transient conformations of a 468 kDa enzyme by specific 1H–13C labeling and fast magic-angle spinning NMR
VL - 141
ER -
TY - JOUR
AB - The bacterial cell wall is composed of the peptidoglycan (PG), a large polymer that maintains the integrity of the bacterial cell. Due to its multi-gigadalton size, heterogeneity, and dynamics, atomic-resolution studies are inherently complex. Solid-state NMR is an important technique to gain insight into its structure, dynamics and interactions. Here, we explore the possibilities to study the PG with ultra-fast (100 kHz) magic-angle spinning NMR. We demonstrate that highly resolved spectra can be obtained, and show strategies to obtain site-specific resonance assignments and distance information. We also explore the use of proton-proton correlation experiments, thus opening the way for NMR studies of intact cell walls without the need for isotope labeling.
AU - Bougault, Catherine
AU - Ayala, Isabel
AU - Vollmer, Waldemar
AU - Simorre, Jean-Pierre
AU - Schanda, Paul
ID - 8409
IS - 1
JF - Journal of Structural Biology
KW - Structural Biology
SN - 1047-8477
TI - Studying intact bacterial peptidoglycan by proton-detected NMR spectroscopy at 100 kHz MAS frequency
VL - 206
ER -
TY - JOUR
AU - Schanda, Paul
AU - Chekmenev, Eduard Y.
ID - 8410
IS - 2
JF - ChemPhysChem
SN - 1439-4235
TI - NMR for Biological Systems
VL - 20
ER -
TY - JOUR
AB - Studying protein dynamics on microsecond‐to‐millisecond (μs‐ms) time scales can provide important insight into protein function. In magic‐angle‐spinning (MAS) NMR, μs dynamics can be visualized by R1p rotating‐frame relaxation dispersion experiments in different regimes of radio‐frequency field strengths: at low RF field strength, isotropic‐chemical‐shift fluctuation leads to “Bloch‐McConnell‐type” relaxation dispersion, while when the RF field approaches rotary resonance conditions bond angle fluctuations manifest as increased R1p rate constants (“Near‐Rotary‐Resonance Relaxation Dispersion”, NERRD). Here we explore the joint analysis of both regimes to gain comprehensive insight into motion in terms of geometric amplitudes, chemical‐shift changes, populations and exchange kinetics. We use a numerical simulation procedure to illustrate these effects and the potential of extracting exchange parameters, and apply the methodology to the study of a previously described conformational exchange process in microcrystalline ubiquitin.
AU - Marion, Dominique
AU - Gauto, Diego F.
AU - Ayala, Isabel
AU - Giandoreggio-Barranco, Karine
AU - Schanda, Paul
ID - 8411
IS - 2
JF - ChemPhysChem
KW - Physical and Theoretical Chemistry
KW - Atomic and Molecular Physics
KW - and Optics
SN - 1439-4235
TI - Microsecond protein dynamics from combined Bloch-McConnell and Near-Rotary-Resonance R1p relaxation-dispersion MAS NMR
VL - 20
ER -
TY - JOUR
AB - Microsecond to millisecond timescale backbone dynamics of the amyloid core residues in Y145Stop human prion protein (PrP) fibrils were investigated by using 15N rotating frame (R1ρ) relaxation dispersion solid‐state nuclear magnetic resonance spectroscopy over a wide range of spin‐lock fields. Numerical simulations enabled the experimental relaxation dispersion profiles for most of the fibril core residues to be modelled by using a two‐state exchange process with a common exchange rate of 1000 s−1, corresponding to protein backbone motion on the timescale of 1 ms, and an excited‐state population of 2 %. We also found that the relaxation dispersion profiles for several amino acids positioned near the edges of the most structured regions of the amyloid core were better modelled by assuming somewhat higher excited‐state populations (∼5–15 %) and faster exchange rate constants, corresponding to protein backbone motions on the timescale of ∼100–300 μs. The slow backbone dynamics of the core residues were evaluated in the context of the structural model of human Y145Stop PrP amyloid.
AU - Shannon, Matthew D.
AU - Theint, Theint
AU - Mukhopadhyay, Dwaipayan
AU - Surewicz, Krystyna
AU - Surewicz, Witold K.
AU - Marion, Dominique
AU - Schanda, Paul
AU - Jaroniec, Christopher P.
ID - 8412
IS - 2
JF - ChemPhysChem
KW - Physical and Theoretical Chemistry
KW - Atomic and Molecular Physics
KW - and Optics
SN - 1439-4235
TI - Conformational dynamics in the core of human Y145Stop prion protein amyloid probed by relaxation dispersion NMR
VL - 20
ER -
TY - JOUR
AB - NMR relaxation dispersion methods provide a holistic way to observe microsecond time-scale protein backbone motion both in solution and in the solid state. Different nuclei (1H and 15N) and different relaxation dispersion techniques (Bloch–McConnell and near-rotary-resonance) give complementary information about the amplitudes and time scales of the conformational dynamics and provide comprehensive insights into the mechanistic details of the structural rearrangements. In this paper, we exemplify the benefits of the combination of various solution- and solid-state relaxation dispersion methods on a microcrystalline protein (α-spectrin SH3 domain), for which we are able to identify and model the functionally relevant conformational rearrangements around the ligand recognition loop occurring on multiple microsecond time scales. The observed loop motions suggest that the SH3 domain exists in a binding-competent conformation in dynamic equilibrium with a sterically impaired ground-state conformation both in solution and in crystalline form. This inherent plasticity between the interconverting macrostates is compatible with a conformational-preselection model and provides new insights into the recognition mechanisms of SH3 domains.
AU - Rovó, Petra
AU - Smith, Colin A.
AU - Gauto, Diego
AU - de Groot, Bert L.
AU - Schanda, Paul
AU - Linser, Rasmus
ID - 8413
IS - 2
JF - Journal of the American Chemical Society
KW - Colloid and Surface Chemistry
KW - Biochemistry
KW - General Chemistry
KW - Catalysis
SN - 0002-7863
TI - Mechanistic insights into microsecond time-scale motion of solid proteins using complementary 15N and 1H relaxation dispersion techniques
VL - 141
ER -
TY - JOUR
AB - We consider billiards obtained by removing three strictly convex obstacles satisfying the non-eclipse condition on the plane. The restriction of the dynamics to the set of non-escaping orbits is conjugated to a subshift on three symbols that provides a natural labeling of all periodic orbits. We study the following inverse problem: does the Marked Length Spectrum (i.e., the set of lengths of periodic orbits together with their labeling), determine the geometry of the billiard table? We show that from the Marked Length Spectrum it is possible to recover the curvature at periodic points of period two, as well as the Lyapunov exponent of each periodic orbit.
AU - Bálint, Péter
AU - De Simoi, Jacopo
AU - Kaloshin, Vadim
AU - Leguil, Martin
ID - 8415
IS - 3
JF - Communications in Mathematical Physics
KW - Mathematical Physics
KW - Statistical and Nonlinear Physics
SN - 0010-3616
TI - Marked length spectrum, homoclinic orbits and the geometry of open dispersing billiards
VL - 374
ER -
TY - JOUR
AB - In this paper, we show that any smooth one-parameter deformations of a strictly convex integrable billiard table Ω0 preserving the integrability near the boundary have to be tangent to a finite dimensional space passing through Ω0.
AU - Huang, Guan
AU - Kaloshin, Vadim
ID - 8416
IS - 2
JF - Moscow Mathematical Journal
SN - 1609-4514
TI - On the finite dimensionality of integrable deformations of strictly convex integrable billiard tables
VL - 19
ER -
TY - JOUR
AB - For the Restricted Circular Planar 3 Body Problem, we show that there exists an open set U in phase space of fixed measure, where the set of initial points which lead to collision is O(μ120) dense as μ→0.
AU - Guardia, Marcel
AU - Kaloshin, Vadim
AU - Zhang, Jianlu
ID - 8418
IS - 2
JF - Archive for Rational Mechanics and Analysis
KW - Mechanical Engineering
KW - Mathematics (miscellaneous)
KW - Analysis
SN - 0003-9527
TI - Asymptotic density of collision orbits in the Restricted Circular Planar 3 Body Problem
VL - 233
ER -
TY - CONF
AB - This report presents the results of a friendly competition for formal verification of continuous and hybrid systems with linear continuous dynamics. The friendly competition took place as part of the workshop Applied Verification for Continuous and Hybrid Systems (ARCH) in 2019. In its third edition, seven tools have been applied to solve six different benchmark problems in the category for linear continuous dynamics (in alphabetical order): CORA, CORA/SX, HyDRA, Hylaa, JuliaReach, SpaceEx, and XSpeed. This report is a snapshot of the current landscape of tools and the types of benchmarks they are particularly suited for. Due to the diversity of problems, we are not ranking tools, yet the presented results provide one of the most complete assessments of tools for the safety verification of continuous and hybrid systems with linear continuous dynamics up to this date.
AU - Althoff, Matthias
AU - Bak, Stanley
AU - Forets, Marcelo
AU - Frehse, Goran
AU - Kochdumper, Niklas
AU - Ray, Rajarshi
AU - Schilling, Christian
AU - Schupp, Stefan
ID - 8570
T2 - EPiC Series in Computing
TI - ARCH-COMP19 Category Report: Continuous and hybrid systems with linear continuous dynamics
VL - 61
ER -
TY - JOUR
AB - In this paper, we introduce a quantum version of the wonderful compactification of a group as a certain noncommutative projective scheme. Our approach stems from the fact that the wonderful compactification encodes the asymptotics of matrix coefficients, and from its realization as a GIT quotient of the Vinberg semigroup. In order to define the wonderful compactification for a quantum group, we adopt a generalized formalism of Proj categories in the spirit of Artin and Zhang. Key to our construction is a quantum version of the Vinberg semigroup, which we define as a q-deformation of a certain Rees algebra, compatible with a standard Poisson structure. Furthermore, we discuss quantum analogues of the stratification of the wonderful compactification by orbits for a certain group action, and provide explicit computations in the case of SL2.
AU - Ganev, Iordan V
ID - 5
IS - 3
JF - Journal of the London Mathematical Society
TI - The wonderful compactification for quantum groups
VL - 99
ER -
TY - JOUR
AB - The order-k Voronoi tessellation of a locally finite set 𝑋⊆ℝ𝑛 decomposes ℝ𝑛 into convex domains whose points have the same k nearest neighbors in X. Assuming X is a stationary Poisson point process, we give explicit formulas for the expected number and total area of faces of a given dimension per unit volume of space. We also develop a relaxed version of discrete Morse theory and generalize by counting only faces, for which the k nearest points in X are within a given distance threshold.
AU - Edelsbrunner, Herbert
AU - Nikitenko, Anton
ID - 5678
IS - 4
JF - Discrete and Computational Geometry
SN - 01795376
TI - Poisson–Delaunay Mosaics of Order k
VL - 62
ER -
TY - JOUR
AB - Pollinators display a remarkable diversity of foraging strategies with flowering plants, from primarily mutualistic interactions to cheating through nectar robbery. Despite numerous studies on the effect of nectar robbing on components of plant fitness, its contribution to reproductive isolation is unclear. We experimentally tested the impact of different pollinator strategies in a natural hybrid zone between two subspecies of Antirrhinum majus with alternate flower colour guides. On either side of a steep cline in flower colour between Antirrhinum majus pseudomajus (magenta) and A. m. striatum (yellow), we quantified the behaviour of all floral visitors at different time points during the flowering season. Using long-run camera surveys, we quantify the impact of nectar robbing on the number of flowers visited per inflorescence and the flower probing time. We further experimentally tested the effect of nectar robbing on female reproductive success by manipulating the intensity of robbing. While robbing increased over time the number of legitimate visitors tended to decrease concomitantly. We found that the number of flowers pollinated on a focal inflorescence decreased with the number of prior robbing events. However, in the manipulative experiment, fruit set and fruit volume did not vary significantly between low robbing and control treatments. Our findings challenge the idea that robbers have a negative impact on plant fitness through female function. This study also adds to our understanding of the components of pollinator-mediated reproductive isolation and the maintenance of Antirrhinum hybrid zones.
AU - Andalo, Christophe
AU - Burrus, Monique
AU - Paute, Sandrine
AU - Lauzeral, Christine
AU - Field, David
ID - 5680
IS - 1
JF - Botany Letters
SN - 23818107
TI - Prevalence of legitimate pollinators and nectar robbers and the consequences for fruit set in an Antirrhinum majus hybrid zone
VL - 166
ER -
TY - JOUR
AB - Tissue morphogenesis is driven by mechanical forces that elicit changes in cell size, shape and motion. The extent by which forces deform tissues critically depends on the rheological properties of the recipient tissue. Yet, whether and how dynamic changes in tissue rheology affect tissue morphogenesis and how they are regulated within the developing organism remain unclear. Here, we show that blastoderm spreading at the onset of zebrafish morphogenesis relies on a rapid, pronounced and spatially patterned tissue fluidization. Blastoderm fluidization is temporally controlled by mitotic cell rounding-dependent cell–cell contact disassembly during the last rounds of cell cleavages. Moreover, fluidization is spatially restricted to the central blastoderm by local activation of non-canonical Wnt signalling within the blastoderm margin, increasing cell cohesion and thereby counteracting the effect of mitotic rounding on contact disassembly. Overall, our results identify a fluidity transition mediated by loss of cell cohesion as a critical regulator of embryo morphogenesis.
AU - Petridou, Nicoletta
AU - Grigolon, Silvia
AU - Salbreux, Guillaume
AU - Hannezo, Edouard B
AU - Heisenberg, Carl-Philipp J
ID - 5789
JF - Nature Cell Biology
SN - 14657392
TI - Fluidization-mediated tissue spreading by mitotic cell rounding and non-canonical Wnt signalling
VL - 21
ER -
TY - JOUR
AB - The partial representation extension problem is a recently introduced generalization of the recognition problem. A circle graph is an intersection graph of chords of a circle. We study the partial representation extension problem for circle graphs, where the input consists of a graph G and a partial representation R′ giving some predrawn chords that represent an induced subgraph of G. The question is whether one can extend R′ to a representation R of the entire graph G, that is, whether one can draw the remaining chords into a partially predrawn representation to obtain a representation of G. Our main result is an O(n3) time algorithm for partial representation extension of circle graphs, where n is the number of vertices. To show this, we describe the structure of all representations of a circle graph using split decomposition. This can be of independent interest.
AU - Chaplick, Steven
AU - Fulek, Radoslav
AU - Klavík, Pavel
ID - 5790
IS - 4
JF - Journal of Graph Theory
SN - 03649024
TI - Extending partial representations of circle graphs
VL - 91
ER -
TY - CHAP
AB - The transcription coactivator, Yes-associated protein (YAP), which is a nuclear effector of the Hippo signaling pathway, has been shown to be a mechano-transducer. By using mutant fish and human 3D spheroids, we have recently demonstrated that YAP is also a mechano-effector. YAP functions in three-dimensional (3D) morphogenesis of organ and global body shape by controlling actomyosin-mediated tissue tension. In this chapter, we present a platform that links the findings in fish embryos with human cells. The protocols for analyzing tissue tension-mediated global body shape/organ morphogenesis in vivo and ex vivo using medaka fish embryos and in vitro using human cell spheroids represent useful tools for unraveling the molecular mechanisms by which YAP functions in regulating global body/organ morphogenesis.
AU - Asaoka, Yoichi
AU - Morita, Hitoshi
AU - Furumoto, Hiroko
AU - Heisenberg, Carl-Philipp J
AU - Furutani-Seiki, Makoto
ED - Hergovich, Alexander
ID - 5793
SN - 978-1-4939-8909-6
T2 - The hippo pathway
TI - Studying YAP-mediated 3D morphogenesis using fish embryos and human spheroids
VL - 1893
ER -
TY - JOUR
AB - We theoretically study the shapes of lipid vesicles confined to a spherical cavity, elaborating a framework based on the so-called limiting shapes constructed from geometrically simple structural elements such as double-membrane walls and edges. Partly inspired by numerical results, the proposed non-compartmentalized and compartmentalized limiting shapes are arranged in the bilayer-couple phase diagram which is then compared to its free-vesicle counterpart. We also compute the area-difference-elasticity phase diagram of the limiting shapes and we use it to interpret shape transitions experimentally observed in vesicles confined within another vesicle. The limiting-shape framework may be generalized to theoretically investigate the structure of certain cell organelles such as the mitochondrion.
AU - Kavcic, Bor
AU - Sakashita, A.
AU - Noguchi, H.
AU - Ziherl, P.
ID - 5817
IS - 4
JF - Soft Matter
SN - 1744-683X
TI - Limiting shapes of confined lipid vesicles
VL - 15
ER -
TY - JOUR
AB - Hippocampus is needed for both spatial working and reference memories. Here, using a radial eight-arm maze, we examined how the combined demand on these memories influenced CA1 place cell assemblies while reference memories were partially updated. This was contrasted with control tasks requiring only working memory or the update of reference memory. Reference memory update led to the reward-directed place field shifts at newly rewarded arms and to the gradual strengthening of firing in passes between newly rewarded arms but not between those passes that included a familiar-rewarded arm. At the maze center, transient network synchronization periods preferentially replayed trajectories of the next chosen arm in reference memory tasks but the previously visited arm in the working memory task. Hence, reference memory demand was uniquely associated with a gradual, goal novelty-related reorganization of place cell assemblies and with trajectory replay that reflected the animal's decision of which arm to visit next.
AU - Xu, Haibing
AU - Baracskay, Peter
AU - O'Neill, Joseph
AU - Csicsvari, Jozsef L
ID - 5828
IS - 1
JF - Neuron
SN - 10974199
TI - Assembly responses of hippocampal CA1 place cells predict learned behavior in goal-directed spatial tasks on the radial eight-arm maze
VL - 101
ER -
TY - JOUR
AB - We give a bound on the ground-state energy of a system of N non-interacting fermions in a three-dimensional cubic box interacting with an impurity particle via point interactions. We show that the change in energy compared to the system in the absence of the impurity is bounded in terms of the gas density and the scattering length of the interaction, independently of N. Our bound holds as long as the ratio of the mass of the impurity to the one of the gas particles is larger than a critical value m∗ ∗≈ 0.36 , which is the same regime for which we recently showed stability of the system.
AU - Moser, Thomas
AU - Seiringer, Robert
ID - 5856
IS - 4
JF - Annales Henri Poincare
SN - 14240637
TI - Energy contribution of a point-interacting impurity in a Fermi gas
VL - 20
ER -
TY - JOUR
AB - A thrackle is a graph drawn in the plane so that every pair of its edges meet exactly once: either at a common end vertex or in a proper crossing. We prove that any thrackle of n vertices has at most 1.3984n edges. Quasi-thrackles are defined similarly, except that every pair of edges that do not share a vertex are allowed to cross an odd number of times. It is also shown that the maximum number of edges of a quasi-thrackle on n vertices is [Formula presented](n−1), and that this bound is best possible for infinitely many values of n.
AU - Fulek, Radoslav
AU - Pach, János
ID - 5857
IS - 4
JF - Discrete Applied Mathematics
SN - 0166218X
TI - Thrackles: An improved upper bound
VL - 259
ER -
TY - JOUR
AB - We consider the motion of a droplet bouncing on a vibrating bath of the same fluid in the presence of a central potential. We formulate a rotation symmetry-reduced description of this system, which allows for the straightforward application of dynamical systems theory tools. As an illustration of the utility of the symmetry reduction, we apply it to a model of the pilot-wave system with a central harmonic force. We begin our analysis by identifying local bifurcations and the onset of chaos. We then describe the emergence of chaotic regions and their merging bifurcations, which lead to the formation of a global attractor. In this final regime, the droplet’s angular momentum spontaneously changes its sign as observed in the experiments of Perrard et al.
AU - Budanur, Nazmi B
AU - Fleury, Marc
ID - 5878
IS - 1
JF - Chaos: An Interdisciplinary Journal of Nonlinear Science
SN - 1054-1500
TI - State space geometry of the chaotic pilot-wave hydrodynamics
VL - 29
ER -
TY - JOUR
AB - Problems involving quantum impurities, in which one or a few particles are interacting with a macroscopic environment, represent a pervasive paradigm, spanning across atomic, molecular, and condensed-matter physics. In this paper we introduce new variational approaches to quantum impurities and apply them to the Fröhlich polaron–a quasiparticle formed out of an electron (or other point-like impurity) in a polar medium, and to the angulon–a quasiparticle formed out of a rotating molecule in a bosonic bath. We benchmark these approaches against established theories, evaluating their accuracy as a function of the impurity-bath coupling.
AU - Li, Xiang
AU - Bighin, Giacomo
AU - Yakaboylu, Enderalp
AU - Lemeshko, Mikhail
ID - 5886
JF - Molecular Physics
SN - 00268976
TI - Variational approaches to quantum impurities: from the Fröhlich polaron to the angulon
ER -
TY - JOUR
AB - Cryptographic security is usually defined as a guarantee that holds except when a bad event with negligible probability occurs, and nothing is guaranteed in that bad case. However, in settings where such failure can happen with substantial probability, one needs to provide guarantees even for the bad case. A typical example is where a (possibly weak) password is used instead of a secure cryptographic key to protect a session, the bad event being that the adversary correctly guesses the password. In a situation with multiple such sessions, a per-session guarantee is desired: any session for which the password has not been guessed remains secure, independently of whether other sessions have been compromised. A new formalism for stating such gracefully degrading security guarantees is introduced and applied to analyze the examples of password-based message authentication and password-based encryption. While a natural per-message guarantee is achieved for authentication, the situation of password-based encryption is more delicate: a per-session confidentiality guarantee only holds against attackers for which the distribution of password-guessing effort over the sessions is known in advance. In contrast, for more general attackers without such a restriction, a strong, composable notion of security cannot be achieved.
AU - Demay, Gregory
AU - Gazi, Peter
AU - Maurer, Ueli
AU - Tackmann, Bjorn
ID - 5887
IS - 1
JF - Journal of Computer Security
SN - 0926227X
TI - Per-session security: Password-based cryptography revisited
VL - 27
ER -
TY - JOUR
AB - We introduce a simple, exactly solvable strong-randomness renormalization group (RG) model for the many-body localization (MBL) transition in one dimension. Our approach relies on a family of RG flows parametrized by the asymmetry between thermal and localized phases. We identify the physical MBL transition in the limit of maximal asymmetry, reflecting the instability of MBL against rare thermal inclusions. We find a critical point that is localized with power-law distributed thermal inclusions. The typical size of critical inclusions remains finite at the transition, while the average size is logarithmically diverging. We propose a two-parameter scaling theory for the many-body localization transition that falls into the Kosterlitz-Thouless universality class, with the MBL phase corresponding to a stable line of fixed points with multifractal behavior.
AU - Goremykina, Anna
AU - Vasseur, Romain
AU - Serbyn, Maksym
ID - 5906
IS - 4
JF - Physical Review Letters
SN - 0031-9007
TI - Analytically solvable renormalization group for the many-body localization transition
VL - 122
ER -
TY - JOUR
AB - Microalgae of the genus Chlorella vulgaris are candidates for the production of lipids for biofuel production. Besides that, Chlorella vulgaris is marketed as protein and vitamin rich food additive. Its potential as a novel expression system for recombinant proteins inspired us to study its asparagine-linked oligosaccharides (N-glycans) by mass spectrometry, chromatography and gas chromatography. Oligomannosidic N-glycans with up to nine mannoses were the structures found in culture collection strains as well as several commercial products. These glycans co-eluted with plant N-glycans in the highly shape selective porous graphitic carbon chromatography. Thus, Chlorella vulgaris generates oligomannosidic N-glycans of the structural type known from land plants and animals. In fact, Man5 (Man5GlcNAc2) served as substrate for GlcNAc-transferase I and a trace of an endogenous structure with terminal GlcNAc was seen. The unusual more linear Man5 structure recently found on glycoproteins of Chlamydomonas reinhardtii occurred - if at all - in traces only. Notably, a majority of the oligomannosidic glycans was multiply O-methylated with 3-O-methyl and 3,6-di-O-methyl mannoses at the non-reducing termini. This modification has so far been neither found on plant nor vertebrate N-glycans. It’s possible immunogenicity raises concerns as to the use of C. vulgaris for production of pharmaceutical glycoproteins.
AU - Mócsai, Réka
AU - Figl, Rudolf
AU - Troschl, Clemens
AU - Strasser, Richard
AU - Svehla, Elisabeth
AU - Windwarder, Markus
AU - Thader, Andreas
AU - Altmann, Friedrich
ID - 5907
IS - 1
JF - Scientific Reports
TI - N-glycans of the microalga Chlorella vulgaris are of the oligomannosidic type but highly methylated
VL - 9
ER -
TY - JOUR
AB - The interorganelle communication mediated by membrane contact sites (MCSs) is an evolutionary hallmark of eukaryotic cells. MCS connections enable the nonvesicular exchange of information between organelles and allow them to coordinate responses to changing cellular environments. In plants, the importance of MCS components in the responses to environmental stress has been widely established, but the molecular mechanisms regulating interorganelle connectivity during stress still remain opaque. In this report, we use the model plant Arabidopsis thaliana to show that ionic stress increases endoplasmic reticulum (ER)–plasma membrane (PM) connectivity by promoting the cortical expansion of synaptotagmin 1 (SYT1)-enriched ER–PM contact sites (S-EPCSs). We define differential roles for the cortical cytoskeleton in the regulation of S-EPCS dynamics and ER–PM connectivity, and we identify the accumulation of phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] at the PM as a molecular signal associated with the ER–PM connectivity changes. Our study highlights the functional conservation of EPCS components and PM phosphoinositides as modulators of ER–PM connectivity in eukaryotes, and uncovers unique aspects of the spatiotemporal regulation of ER–PM connectivity in plants.
AU - Lee, Eunkyoung
AU - Vanneste, Steffen
AU - Pérez-Sancho, Jessica
AU - Benitez-Fuente, Francisco
AU - Strelau, Matthew
AU - Macho, Alberto P.
AU - Botella, Miguel A.
AU - Friml, Jiří
AU - Rosado, Abel
ID - 5908
IS - 4
JF - Proceedings of the National Academy of Sciences of the United States of America
TI - Ionic stress enhances ER–PM connectivity via phosphoinositide-associated SYT1 contact site expansion in Arabidopsis
VL - 116
ER -
TY - JOUR
AB - Empirical data suggest that inversions in many species contain genes important for intraspecific divergence and speciation, yet mechanisms of evolution remain unclear. While genes inside an inversion are tightly linked, inversions are not static but evolve separately from the rest of the genome by new mutations, recombination within arrangements, and gene flux between arrangements. Inversion polymorphisms are maintained by different processes, for example, divergent or balancing selection, or a mix of multiple processes. Moreover, the relative roles of selection, drift, mutation, and recombination will change over the lifetime of an inversion and within its area of distribution. We believe inversions are central to the evolution of many species, but we need many more data and new models to understand the complex mechanisms involved.
AU - Faria, Rui
AU - Johannesson, Kerstin
AU - Butlin, Roger K.
AU - Westram, Anja M
ID - 5911
IS - 3
JF - Trends in Ecology and Evolution
SN - 01695347
TI - Evolving inversions
VL - 34
ER -
TY - JOUR
AB - The hairpin instability of a jet in a crossflow (JICF) for a low jet-to-crossflow velocity ratio is investigated experimentally for a velocity ratio range of R ∈ (0.14, 0.75) and crossflow Reynolds numbers ReD ∈ (260, 640). From spectral analysis we characterize the Strouhal number and amplitude of the hairpin instability as a function of R and ReD. We demonstrate that the dynamics of the hairpins is well described by the Landau model, and, hence, that the instability occurs through Hopf bifurcation, similarly to other hydrodynamical oscillators such as wake behind different bluff bodies. Using the Landau model, we determine the precise threshold values of hairpin shedding. We also study the spatial dependence of this hydrodynamical instability, which shows a global behaviour.
AU - Klotz, Lukasz
AU - Gumowski, Konrad
AU - Wesfreid, José Eduardo
ID - 5943
JF - Journal of Fluid Mechanics
TI - Experiments on a jet in a crossflow in the low-velocity-ratio regime
VL - 863
ER -
TY - JOUR
AB - Understanding the thermodynamics of the duplication process is a fundamental step towards a comprehensive physical theory of biological systems. However, the immense complexity of real cells obscures the fundamental tensions between energy gradients and entropic contributions that underlie duplication. The study of synthetic, feasible systems reproducing part of the key ingredients of living entities but overcoming major sources of biological complexity is of great relevance to deepen the comprehension of the fundamental thermodynamic processes underlying life and its prevalence. In this paper an abstract—yet realistic—synthetic system made of small synthetic protocell aggregates is studied in detail. A fundamental relation between free energy and entropic gradients is derived for a general, non-equilibrium scenario, setting the thermodynamic conditions for the occurrence and prevalence of duplication phenomena. This relation sets explicitly how the energy gradients invested in creating and maintaining structural—and eventually, functional—elements of the system must always compensate the entropic gradients, whose contributions come from changes in the translational, configurational, and macrostate entropies, as well as from dissipation due to irreversible transitions. Work/energy relations are also derived, defining lower bounds on the energy required for the duplication event to take place. A specific example including real ternary emulsions is provided in order to grasp the orders of magnitude involved in the problem. It is found that the minimal work invested over the system to trigger a duplication event is around ~ 10−13J , which results, in the case of duplication of all the vesicles contained in a liter of emulsion, in an amount of energy around ~ 1kJ . Without aiming to describe a truly biological process of duplication, this theoretical contribution seeks to explicitly define and identify the key actors that participate in it.
AU - Corominas-Murtra, Bernat
ID - 5944
IS - 1
JF - Life
TI - Thermodynamics of duplication thresholds in synthetic protocell systems
VL - 9
ER -
TY - JOUR
AB - In developing organisms, spatially prescribed cell identities are thought to be determined by the expression levels of multiple genes. Quantitative tests of this idea, however, require a theoretical framework capable of exposing the rules and precision of cell specification over developmental time. We use the gap gene network in the early fly embryo as an example to show how expression levels of the four gap genes can be jointly decoded into an optimal specification of position with 1% accuracy. The decoder correctly predicts, with no free parameters, the dynamics of pair-rule expression patterns at different developmental time points and in various mutant backgrounds. Precise cellular identities are thus available at the earliest stages of development, contrasting the prevailing view of positional information being slowly refined across successive layers of the patterning network. Our results suggest that developmental enhancers closely approximate a mathematically optimal decoding strategy.
AU - Petkova, Mariela D.
AU - Tkacik, Gasper
AU - Bialek, William
AU - Wieschaus, Eric F.
AU - Gregor, Thomas
ID - 5945
IS - 4
JF - Cell
TI - Optimal decoding of cellular identities in a genetic network
VL - 176
ER -
TY - CONF
AB - Graph algorithms applied in many applications, including social networks, communication networks, VLSI design, graphics, and several others, require dynamic modifications - addition and removal of vertices and/or edges - in the graph. This paper presents a novel concurrent non-blocking algorithm to implement a dynamic unbounded directed graph in a shared-memory machine. The addition and removal operations of vertices and edges are lock-free. For a finite sized graph, the lookup operations are wait-free. Most significant component of the presented algorithm is the reachability query in a concurrent graph. The reachability queries in our algorithm are obstruction-free and thus impose minimal additional synchronization cost over other operations. We prove that each of the data structure operations are linearizable. We extensively evaluate a sample C/C++ implementation of the algorithm through a number of micro-benchmarks. The experimental results show that the proposed algorithm scales well with the number of threads and on an average provides 5 to 7x performance improvement over a concurrent graph implementation using coarse-grained locking.
AU - Chatterjee, Bapi
AU - Peri, Sathya
AU - Sa, Muktikanta
AU - Singhal, Nandini
ID - 5947
SN - 978-1-4503-6094-4
T2 - ACM International Conference Proceeding Series
TI - A simple and practical concurrent non-blocking unbounded graph with linearizable reachability queries
ER -
TY - CONF
AB - We study the termination problem for nondeterministic probabilistic programs. We consider the bounded termination problem that asks whether the supremum of the expected termination time over all schedulers is bounded. First, we show that ranking supermartingales (RSMs) are both sound and complete for proving bounded termination over nondeterministic probabilistic programs. For nondeterministic probabilistic programs a previous result claimed that RSMs are not complete for bounded termination, whereas our result corrects the previous flaw and establishes completeness with a rigorous proof. Second, we present the first sound approach to establish lower bounds on expected termination time through RSMs.
AU - Fu, Hongfei
AU - Chatterjee, Krishnendu
ID - 5948
T2 - International Conference on Verification, Model Checking, and Abstract Interpretation
TI - Termination of nondeterministic probabilistic programs
VL - 11388
ER -
TY - JOUR
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 (with 𝑂(𝑛8) being a crude bound on the run-time) 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 - 5986
IS - 4
JF - Discrete & Computational Geometry
SN - 0179-5376
TI - A proof of the orbit conjecture for flipping edge-labelled triangulations
VL - 61
ER -
TY - JOUR
AB - Speed of sound waves in gases and liquids are governed by the compressibility of the medium. There exists another type of non-dispersive wave where the wave speed depends on stress instead of elasticity of the medium. A well-known example is the Alfven wave, which propagates through plasma permeated by a magnetic field with the speed determined by magnetic tension. An elastic analogue of Alfven waves has been predicted in a flow of dilute polymer solution where the elastic stress of the stretching polymers determines the elastic wave speed. Here we present quantitative evidence of elastic Alfven waves in elastic turbulence of a viscoelastic creeping flow between two obstacles in channel flow. The key finding in the experimental proof is a nonlinear dependence of the elastic wave speed cel on the Weissenberg number Wi, which deviates from predictions based on a model of linear polymer elasticity.
AU - Varshney, Atul
AU - Steinberg, Victor
ID - 6014
JF - Nature Communications
SN - 2041-1723
TI - Elastic alfven waves in elastic turbulence
VL - 10
ER -
TY - JOUR
AB - The evolution of new species is made easier when traits under divergent ecological selection are also mating cues. Such ecological mating cues are now considered more common than previously thought, but we still know little about the genetic changes underlying their evolution or more generally about the genetic basis for assortative mating behaviors. Both tight physical linkage and the existence of large-effect preference loci will strengthen genetic associations between behavioral and ecological barriers, promoting the evolution of assortative mating. The warning patterns of Heliconius melpomene and H. cydno are under disruptive selection due to increased predation of nonmimetic hybrids and are used during mate recognition. We carried out a genome-wide quantitative trait locus (QTL) analysis of preference behaviors between these species and showed that divergent male preference has a simple genetic basis. We identify three QTLs that together explain a large proportion (approximately 60%) of the difference in preference behavior observed between the parental species. One of these QTLs is just 1.2 (0-4.8) centiMorgans (cM) from the major color pattern gene optix, and, individually, all three have a large effect on the preference phenotype. Genomic divergence between H. cydno and H. melpomene is high but broadly heterogenous, and admixture is reduced at the preference-optix color pattern locus but not the other preference QTLs. The simple genetic architecture we reveal will facilitate the evolution and maintenance of new species despite ongoing gene flow by coupling behavioral and ecological aspects of reproductive isolation.
AU - Merrill, Richard M.
AU - Rastas, Pasi
AU - Martin, Simon H.
AU - Melo Hurtado, Maria C
AU - Barker, Sarah
AU - Davey, John
AU - Mcmillan, W. Owen
AU - Jiggins, Chris D.
ID - 6022
IS - 2
JF - PLoS Biology
TI - Genetic dissection of assortative mating behavior
VL - 17
ER -
TY - JOUR
AB - Multicellular development requires coordinated cell polarization relative to body axes, and translation to oriented cell division 1–3 . In plants, it is unknown how cell polarities are connected to organismal axes and translated to division. Here, we identify Arabidopsis SOSEKI proteins that integrate apical–basal and radial organismal axes to localize to polar cell edges. Localization does not depend on tissue context, requires cell wall integrity and is defined by a transferrable, protein-specific motif. A Domain of Unknown Function in SOSEKI proteins resembles the DIX oligomerization domain in the animal Dishevelled polarity regulator. The DIX-like domain self-interacts and is required for edge localization and for influencing division orientation, together with a second domain that defines the polar membrane domain. Our work shows that SOSEKI proteins locally interpret global polarity cues and can influence cell division orientation. Furthermore, this work reveals that, despite fundamental differences, cell polarity mechanisms in plants and animals converge on a similar protein domain.
AU - Yoshida, Saiko
AU - Van Der Schuren, Alja
AU - Van Dop, Maritza
AU - Van Galen, Luc
AU - Saiga, Shunsuke
AU - Adibi, Milad
AU - Möller, Barbara
AU - Ten Hove, Colette A.
AU - Marhavy, Peter
AU - Smith, Richard
AU - Friml, Jiří
AU - Weijers, Dolf
ID - 6023
IS - 2
JF - Nature Plants
TI - A SOSEKI-based coordinate system interprets global polarity cues in arabidopsis
VL - 5
ER -
TY - JOUR
AB - Non-canonical Wnt signaling plays a central role for coordinated cell polarization and directed migration in metazoan development. While spatiotemporally restricted activation of non-canonical Wnt-signaling drives cell polarization in epithelial tissues, it remains unclear whether such instructive activity is also critical for directed mesenchymal cell migration. Here, we developed a light-activated version of the non-canonical Wnt receptor Frizzled 7 (Fz7) to analyze how restricted activation of non-canonical Wnt signaling affects directed anterior axial mesendoderm (prechordal plate, ppl) cell migration within the zebrafish gastrula. We found that Fz7 signaling is required for ppl cell protrusion formation and migration and that spatiotemporally restricted ectopic activation is capable of redirecting their migration. Finally, we show that uniform activation of Fz7 signaling in ppl cells fully rescues defective directed cell migration in fz7 mutant embryos. Together, our findings reveal that in contrast to the situation in epithelial cells, non-canonical Wnt signaling functions permissively rather than instructively in directed mesenchymal cell migration during gastrulation.
AU - Capek, Daniel
AU - Smutny, Michael
AU - Tichy, Alexandra Madelaine
AU - Morri, Maurizio
AU - Janovjak, Harald L
AU - Heisenberg, Carl-Philipp J
ID - 6025
JF - eLife
TI - Light-activated Frizzled7 reveals a permissive role of non-canonical wnt signaling in mesendoderm cell migration
VL - 8
ER -
TY - JOUR
AB - We give a construction allowing us to build local renormalized solutions to general quasilinear stochastic PDEs within the theory of regularity structures, thus greatly generalizing the recent results of [1, 5, 11]. Loosely speaking, our construction covers quasilinear variants of all classes of equations for which the general construction of [3, 4, 7] applies, including in particular one‐dimensional systems with KPZ‐type nonlinearities driven by space‐time white noise. In a less singular and more specific case, we furthermore show that the counterterms introduced by the renormalization procedure are given by local functionals of the solution. The main feature of our construction is that it allows exploitation of a number of existing results developed for the semilinear case, so that the number of additional arguments it requires is relatively small.
AU - Gerencser, Mate
AU - Hairer, Martin
ID - 6028
IS - 9
JF - Communications on Pure and Applied Mathematics
TI - A solution theory for quasilinear singular SPDEs
VL - 72
ER -
TY - JOUR
AB - Protein micropatterning has become an important tool for many biomedical applications as well as in academic research. Current techniques that allow to reduce the feature size of patterns below 1 μm are, however, often costly and require sophisticated equipment. We present here a straightforward and convenient method to generate highly condensed nanopatterns of proteins without the need for clean room facilities or expensive equipment. Our approach is based on nanocontact printing and allows for the fabrication of protein patterns with feature sizes of 80 nm and periodicities down to 140 nm. This was made possible by the use of the material X-poly(dimethylsiloxane) (X-PDMS) in a two-layer stamp layout for protein printing. In a proof of principle, different proteins at various scales were printed and the pattern quality was evaluated by atomic force microscopy (AFM) and super-resolution fluorescence microscopy.
AU - Lindner, Marco
AU - Tresztenyak, Aliz
AU - Fülöp, Gergö
AU - Jahr, Wiebke
AU - Prinz, Adrian
AU - Prinz, Iris
AU - Danzl, Johann G
AU - Schütz, Gerhard J.
AU - Sevcsik, Eva
ID - 6029
JF - Frontiers in Chemistry
TI - A fast and simple contact printing approach to generate 2D protein nanopatterns
VL - 6
ER -
TY - CONF
AB - We present JuliaReach, a toolbox for set-based reachability analysis of dynamical systems. JuliaReach consists of two main packages: Reachability, containing implementations of reachability algorithms for continuous and hybrid systems, and LazySets, a standalone library that implements state-of-the-art algorithms for calculus with convex sets. The library offers both concrete and lazy set representations, where the latter stands for the ability to delay set computations until they are needed. The choice of the programming language Julia and the accompanying documentation of our toolbox allow researchers to easily translate set-based algorithms from mathematics to software in a platform-independent way, while achieving runtime performance that is comparable to statically compiled languages. Combining lazy operations in high dimensions and explicit computations in low dimensions, JuliaReach can be applied to solve complex, large-scale problems.
AU - Bogomolov, Sergiy
AU - Forets, Marcelo
AU - Frehse, Goran
AU - Potomkin, Kostiantyn
AU - Schilling, Christian
ID - 6035
KW - reachability analysis
KW - hybrid systems
KW - lazy computation
SN - 9781450362825
T2 - Proceedings of the 22nd International Conference on Hybrid Systems: Computation and Control
TI - JuliaReach: A toolbox for set-based reachability
VL - 22
ER -
TY - CONF
AB - Static program analyzers are increasingly effective in checking correctness properties of programs and reporting any errors found, often in the form of error traces. However, developers still spend a significant amount of time on debugging. This involves processing long error traces in an effort to localize a bug to a relatively small part of the program and to identify its cause. In this paper, we present a technique for automated fault localization that, given a program and an error trace, efficiently narrows down the cause of the error to a few statements. These statements are then ranked in terms of their suspiciousness. Our technique relies only on the semantics of the given program and does not require any test cases or user guidance. In experiments on a set of C benchmarks, we show that our technique is effective in quickly isolating the cause of error while out-performing other state-of-the-art fault-localization techniques.
AU - Christakis, Maria
AU - Heizmann, Matthias
AU - Mansur, Muhammad Numair
AU - Schilling, Christian
AU - Wüstholz, Valentin
ID - 6042
T2 - 25th International Conference on Tools and Algorithms for the Construction and Analysis of Systems
TI - Semantic fault localization and suspiciousness ranking
VL - 11427
ER -
TY - JOUR
AB - Sudden stress often triggers diverse, temporally structured gene expression responses in microbes, but it is largely unknown how variable in time such responses are and if genes respond in the same temporal order in every single cell. Here, we quantified timing variability of individual promoters responding to sublethal antibiotic stress using fluorescent reporters, microfluidics, and time‐lapse microscopy. We identified lower and upper bounds that put definite constraints on timing variability, which varies strongly among promoters and conditions. Timing variability can be interpreted using results from statistical kinetics, which enable us to estimate the number of rate‐limiting molecular steps underlying different responses. We found that just a few critical steps control some responses while others rely on dozens of steps. To probe connections between different stress responses, we then tracked the temporal order and response time correlations of promoter pairs in individual cells. Our results support that, when bacteria are exposed to the antibiotic nitrofurantoin, the ensuing oxidative stress and SOS responses are part of the same causal chain of molecular events. In contrast, under trimethoprim, the acid stress response and the SOS response are part of different chains of events running in parallel. Our approach reveals fundamental constraints on gene expression timing and provides new insights into the molecular events that underlie the timing of stress responses.
AU - Mitosch, Karin
AU - Rieckh, Georg
AU - Bollenbach, Mark Tobias
ID - 6046
IS - 2
JF - Molecular systems biology
TI - Temporal order and precision of complex stress responses in individual bacteria
VL - 15
ER -
TY - JOUR
AB - In this article it is shown that large systems with many interacting units endowing multiple phases display self-oscillations in the presence of linear feedback between the control and order parameters, where an Andronov–Hopf bifurcation takes over the phase transition. This is simply illustrated through the mean field Landau theory whose feedback dynamics turn out to be described by the Van der Pol equation and it is then validated for the fully connected Ising model following heat bath dynamics. Despite its simplicity, this theory accounts potentially for a rich range of phenomena: here it is applied to describe in a stylized way (i) excess demand-price cycles due to strong herding in a simple agent-based market model; (ii) congestion waves in queuing networks triggered by user feedback to delays in overloaded conditions; and (iii) metabolic network oscillations resulting from cell growth control in a bistable phenotypic landscape.
AU - De Martino, Daniele
ID - 6049
IS - 4
JF - Journal of Physics A: Mathematical and Theoretical
TI - Feedback-induced self-oscillations in large interacting systems subjected to phase transitions
VL - 52
ER -
TY - JOUR
AB - We answer a question of David Hilbert: given two circles it is not possible in general to construct their centers using only a straightedge. On the other hand, we give infinitely many families of pairs of circles for which such construction is possible.
AU - Akopyan, Arseniy
AU - Fedorov, Roman
ID - 6050
JF - Proceedings of the American Mathematical Society
TI - Two circles and only a straightedge
VL - 147
ER -
TY - JOUR
AB - Expansion microscopy is a relatively new approach to super-resolution imaging that uses expandable hydrogels to isotropically increase the physical distance between fluorophores in biological samples such as cell cultures or tissue slices. The classic gel recipe results in an expansion factor of ~4×, with a resolution of 60–80 nm. We have recently developed X10 microscopy, which uses a gel that achieves an expansion factor of ~10×, with a resolution of ~25 nm. Here, we provide a step-by-step protocol for X10 expansion microscopy. A typical experiment consists of seven sequential stages: (i) immunostaining, (ii) anchoring, (iii) polymerization, (iv) homogenization, (v) expansion, (vi) imaging, and (vii) validation. The protocol presented here includes recommendations for optimization, pitfalls and their solutions, and detailed guidelines that should increase reproducibility. Although our protocol focuses on X10 expansion microscopy, we detail which of these suggestions are also applicable to classic fourfold expansion microscopy. We exemplify our protocol using primary hippocampal neurons from rats, but our approach can be used with other primary cells or cultured cell lines of interest. This protocol will enable any researcher with basic experience in immunostainings and access to an epifluorescence microscope to perform super-resolution microscopy with X10. The procedure takes 3 d and requires ~5 h of actively handling the sample for labeling and expansion, and another ~3 h for imaging and analysis.
AU - Truckenbrodt, Sven M
AU - Sommer, Christoph M
AU - Rizzoli, Silvio O
AU - Danzl, Johann G
ID - 6052
IS - 3
JF - Nature Protocols
TI - A practical guide to optimization in X10 expansion microscopy
VL - 14
ER -
TY - JOUR
AB - Recent technical developments in the fields of quantum electromechanics and optomechanics have spawned nanoscale mechanical transducers with the sensitivity to measure mechanical displacements at the femtometre scale and the ability to convert electromagnetic signals at the single photon level. A key challenge in this field is obtaining strong coupling between motion and electromagnetic fields without adding additional decoherence. Here we present an electromechanical transducer that integrates a high-frequency (0.42 GHz) hypersonic phononic crystal with a superconducting microwave circuit. The use of a phononic bandgap crystal enables quantum-level transduction of hypersonic mechanical motion and concurrently eliminates decoherence caused by acoustic radiation. Devices with hypersonic mechanical frequencies provide a natural pathway for integration with Josephson junction quantum circuits, a leading quantum computing technology, and nanophotonic systems capable of optical networking and distributing quantum information.
AU - Kalaee, Mahmoud
AU - Mirhosseini, Mohammad
AU - Dieterle, Paul B.
AU - Peruzzo, Matilda
AU - Fink, Johannes M
AU - Painter, Oskar
ID - 6053
IS - 4
JF - Nature Nanotechnology
SN - 1748-3387
TI - Quantum electromechanics of a hypersonic crystal
VL - 14
ER -
TY - DATA
AU - Vicoso, Beatriz
ID - 6060
TI - Supplementary data for "Sex-biased gene expression and dosage compensation on the Artemia franciscana Z-chromosome" (Huylman, Toups et al., 2019).
ER -
TY - DATA
AB - Open the files in Jupyter Notebook (reccomended https://www.anaconda.com/distribution/#download-section with Python 3.7).
AU - Nardin, Michele
ID - 6062
TI - Supplementary Code and Data for the paper "The Entorhinal Cognitive Map is Attracted to Goals"
ER -
TY - JOUR
AB - Electron transport in two-dimensional conducting materials such as graphene, with dominant electron–electron interaction, exhibits unusual vortex flow that leads to a nonlocal current-field relation (negative resistance), distinct from the classical Ohm’s law. The transport behavior of these materials is best described by low Reynolds number hydrodynamics, where the constitutive pressure–speed relation is Stoke’s law. Here we report evidence of such vortices observed in a viscous flow of Newtonian fluid in a microfluidic device consisting of a rectangular cavity—analogous to the electronic system. We extend our experimental observations to elliptic cavities of different eccentricities, and validate them by numerically solving bi-harmonic equation obtained for the viscous flow with no-slip boundary conditions. We verify the existence of a predicted threshold at which vortices appear. Strikingly, we find that a two-dimensional theoretical model captures the essential features of three-dimensional Stokes flow in experiments.
AU - Mayzel, Jonathan
AU - Steinberg, Victor
AU - Varshney, Atul
ID - 6069
JF - Nature Communications
SN - 2041-1723
TI - Stokes flow analogous to viscous electron current in graphene
VL - 10
ER -
TY - THES
AB - Transcription factors, by binding to specific sequences on the DNA, control the precise spatio-temporal expression of genes inside a cell. However, this specificity is limited, leading to frequent incorrect binding of transcription factors that might have deleterious consequences on the cell. By constructing a biophysical model of TF-DNA binding in the context of gene regulation, I will first explore how regulatory constraints can strongly shape the distribution of a population in sequence space. Then, by directly linking this to a picture of multiple types of transcription factors performing their functions simultaneously inside the cell, I will explore the extent of regulatory crosstalk -- incorrect binding interactions between transcription factors and binding sites that lead to erroneous regulatory states -- and understand the constraints this places on the design of regulatory systems. I will then develop a generic theoretical framework to investigate the coevolution of multiple transcription factors and multiple binding sites, in the context of a gene regulatory network that performs a certain function. As a particular tractable version of this problem, I will consider the evolution of two transcription factors when they transmit upstream signals to downstream target genes. Specifically, I will describe the evolutionary steady states and the evolutionary pathways involved, along with their timescales, of a system that initially undergoes a transcription factor duplication event. To connect this important theoretical model to the prominent biological event of transcription factor duplication giving rise to paralogous families, I will then describe a bioinformatics analysis of C2H2 Zn-finger transcription factors, a major family in humans, and focus on the patterns of evolution that paralogs have undergone in their various protein domains in the recent past.
AU - Prizak, Roshan
ID - 6071
TI - Coevolution of transcription factors and their binding sites in sequence space
ER -
TY - JOUR
AB - We study the problem of automatically detecting if a given multi-class classifier operates outside of its specifications (out-of-specs), i.e. on input data from a different distribution than what it was trained for. This is an important problem to solve on the road towards creating reliable computer vision systems for real-world applications, because the quality of a classifier’s predictions cannot be guaranteed if it operates out-of-specs. Previously proposed methods for out-of-specs detection make decisions on the level of single inputs. This, however, is insufficient to achieve low false positive rate and high false negative rates at the same time. In this work, we describe a new procedure named KS(conf), based on statistical reasoning. Its main component is a classical Kolmogorov–Smirnov test that is applied to the set of predicted confidence values for batches of samples. Working with batches instead of single samples allows increasing the true positive rate without negatively affecting the false positive rate, thereby overcoming a crucial limitation of single sample tests. We show by extensive experiments using a variety of convolutional network architectures and datasets that KS(conf) reliably detects out-of-specs situations even under conditions where other tests fail. It furthermore has a number of properties that make it an excellent candidate for practical deployment: it is easy to implement, adds almost no overhead to the system, works with any classifier that outputs confidence scores, and requires no a priori knowledge about how the data distribution could change.
AU - Sun, Rémy
AU - Lampert, Christoph
ID - 6944
JF - International Journal of Computer Vision
SN - 0920-5691
TI - KS(conf): A light-weight test if a multiclass classifier operates outside of its specifications
VL - 128
ER -
TY - JOUR
AB - We study few-body bound states of charged particles subject to attractive zero-range/short-range plus repulsive Coulomb interparticle forces. The characteristic length scales of the system at zero energy are set by the Coulomb length scale D and the Coulomb-modified effective range r eff. We study shallow bound states of charged particles with D >> r eff and show that these systems obey universal scaling laws different from neutral particles. An accurate description of these states requires both the Coulomb-modified scattering length and the effective range unless the Coulomb interaction is very weak (D -> ). Our findings are relevant for bound states whose spatial extent is significantly larger than the range of the attractive potential. These states enjoy universality – their character is independent of the shape of the short-range potential.
AU - Schmickler, C.H.
AU - Hammer, H.-W.
AU - Volosniev, Artem
ID - 6955
JF - Physics Letters B
SN - 0370-2693
TI - Universal physics of bound states of a few charged particles
VL - 798
ER -
TY - THES
AB - In many shear flows like pipe flow, plane Couette flow, plane Poiseuille flow, etc. turbulence emerges subcritically. Here, when subjected to strong enough perturbations, the flow becomes turbulent in spite of the laminar base flow being linearly stable. The nature of this instability has puzzled the scientific community for decades. At onset, turbulence appears in localized patches and flows are spatio-temporally intermittent. In pipe flow the localized turbulent structures are referred to as puffs and in planar flows like plane Couette and channel flow, patches arise in the form of localized oblique bands. In this thesis, we study the onset of turbulence in channel flow in direct numerical simulations from a dynamical system theory perspective, as well as by performing experiments in a large aspect ratio channel.
The aim of the experimental work is to determine the critical Reynolds number where turbulence first becomes sustained. Recently, the onset of turbulence has been described in analogy to absorbing state phase transition (i.e. directed percolation). In particular, it has been shown that the critical point can be estimated from the competition between spreading and decay processes. Here, by performing experiments, we identify the mechanisms underlying turbulence proliferation in channel flow and find the critical Reynolds number, above which turbulence becomes sustained. Above the critical point, the continuous growth at the tip of the stripes outweighs the stochastic shedding of turbulent patches at the tail and the stripes expand. For growing stripes, the probability to decay decreases while the probability of stripe splitting increases. Consequently, and unlike for the puffs in pipe flow, neither of these two processes is time-independent i.e. memoryless. Coupling between stripe expansion and creation of new stripes via splitting leads to a significantly lower critical point ($Re_c=670+/-10$) than most earlier studies suggest.
While the above approach sheds light on how turbulence first becomes sustained, it provides no insight into the origin of the stripes themselves. In the numerical part of the thesis we investigate how turbulent stripes form from invariant solutions of the Navier-Stokes equations. The origin of these turbulent stripes can be identified by applying concepts from the dynamical system theory. In doing so, we identify the exact coherent structures underlying stripes and their bifurcations and how they give rise to the turbulent attractor in phase space. We first report a family of localized nonlinear traveling wave solutions of the Navier-Stokes equations in channel flow. These solutions show structural similarities with turbulent stripes in experiments like obliqueness, quasi-streamwise streaks and vortices, etc. A parametric study of these traveling wave solution is performed, with parameters like Reynolds number, stripe tilt angle and domain size, including the stability of the solutions. These solutions emerge through saddle-node bifurcations and form a phase space skeleton for the turbulent stripes observed in the experiments. The lower branches of these TW solutions at different tilt angles undergo Hopf bifurcation and new solutions branches of relative periodic orbits emerge. These RPO solutions do not belong to the same family and therefore the routes to chaos for different angles are different.
In shear flows, turbulence at onset is transient in nature. Consequently,turbulence can not be tracked to lower Reynolds numbers, where the dynamics may simplify. Before this happens, turbulence becomes short-lived and laminarizes. In the last part of the thesis, we show that using numerical simulations we can continue turbulent stripes in channel flow past the 'relaminarization barrier' all the way to their origin. Here, turbulent stripe dynamics simplifies and the fluctuations are no longer stochastic and the stripe settles down to a relative periodic orbit. This relative periodic orbit originates from the aforementioned traveling wave solutions. Starting from the relative periodic orbit, a small increase in speed i.e. Reynolds number gives rise to chaos and the attractor dimension sharply increases in contrast to the classical transition scenario where the instabilities affect the flow globally and give rise to much more gradual route to turbulence.
AU - Paranjape, Chaitanya S
ID - 6957
KW - Instabilities
KW - Turbulence
KW - Nonlinear dynamics
TI - Onset of turbulence in plane Poiseuille flow
ER -
TY - JOUR
AB - We give fault-tolerant algorithms for establishing synchrony in distributed systems in which each of thennodes has its own clock. Our algorithms operate in a very strong fault model: we require self-stabilisation, i.e.,the initial state of the system may be arbitrary, and there can be up to f 0, where ‖.‖ is the unform norm.
A polynomial-time algorithm for recognizing weak embeddings has recently been found by Fulek and Kynčl. It reduces the problem to solving a system of linear equations over Z2. It runs in O(n2ω)≤ O(n4.75) time, where ω ∈ [2,2.373) is the matrix multiplication exponent and n is the number of vertices and edges of G. We improve the running time to O(n log n). Our algorithm is also conceptually simpler: We perform a sequence of local operations that gradually “untangles” the image ϕ(G) into an embedding ψ(G) or reports that ϕ is not a weak embedding. It combines local constraints on the orientation of subgraphs directly, thereby eliminating the need for solving large systems of linear equations.
AU - Akitaya, Hugo
AU - Fulek, Radoslav
AU - Tóth, Csaba
ID - 6982
IS - 4
JF - ACM Transactions on Algorithms
TI - Recognizing weak embeddings of graphs
VL - 15
ER -
TY - JOUR
AB - Malaria, a disease caused by parasites of the Plasmodium genus, begins when Plasmodium-infected mosquitoes inject malaria sporozoites while searching for blood. Sporozoites migrate from the skin via blood to the liver, infect hepatocytes, and form liver stages which in mice 48 h later escape into blood and cause clinical malaria. Vaccine-induced activated or memory CD8 T cells are capable of locating and eliminating all liver stages in 48 h, thus preventing the blood-stage disease. However, the rules of how CD8 T cells are able to locate all liver stages within a relatively short time period remains poorly understood. We recently reported formation of clusters consisting of variable numbers of activated CD8 T cells around Plasmodium yoelii (Py)-infected hepatocytes. Using a combination of experimental data and mathematical models we now provide additional insights into mechanisms of formation of these clusters. First, we show that a model in which cluster formation is driven exclusively by T-cell-extrinsic factors, such as variability in “attractiveness” of different liver stages, cannot explain distribution of cluster sizes in different experimental conditions. In contrast, the model in which cluster formation is driven by the positive feedback loop (i.e., larger clusters attract more CD8 T cells) can accurately explain the available data. Second, while both Py-specific CD8 T cells and T cells of irrelevant specificity (non-specific CD8 T cells) are attracted to the clusters, we found no evidence that non-specific CD8 T cells play a role in cluster formation. Third and finally, mathematical modeling suggested that formation of clusters occurs rapidly, within few hours after adoptive transfer of CD8 T cells, thus illustrating high efficiency of CD8 T cells in locating their targets in complex peripheral organs, such as the liver. Taken together, our analysis provides novel insights into and attempts to discriminate between alternative mechanisms driving the formation of clusters of antigen-specific CD8 T cells in the liver.
AU - Kelemen, Réka K
AU - Rajakaruna, H
AU - Cockburn, IA
AU - Ganusov, VV
ID - 6983
JF - Frontiers in Immunology
SN - 1664-3224
TI - Clustering of activated CD8 T cells around Malaria-infected hepatocytes is rapid and is driven by antigen-specific cells
VL - 10
ER -
TY - CONF
AB - In this paper, we introduce a novel method to interpret recurrent neural networks (RNNs), particularly long short-term memory networks (LSTMs) at the cellular level. We propose a systematic pipeline for interpreting individual hidden state dynamics within the network using response characterization methods. The ranked contribution of individual cells to the network's output is computed by analyzing a set of interpretable metrics of their decoupled step and sinusoidal responses. As a result, our method is able to uniquely identify neurons with insightful dynamics, quantify relationships between dynamical properties and test accuracy through ablation analysis, and interpret the impact of network capacity on a network's dynamical distribution. Finally, we demonstrate the generalizability and scalability of our method by evaluating a series of different benchmark sequential datasets.
AU - Hasani, Ramin
AU - Amini, Alexander
AU - Lechner, Mathias
AU - Naser, Felix
AU - Grosu, Radu
AU - Rus, Daniela
ID - 6985
SN - 9781728119854
T2 - Proceedings of the International Joint Conference on Neural Networks
TI - Response characterization for auditing cell dynamics in long short-term memory networks
ER -
TY - JOUR
AB - Li-Nadler proposed a conjecture about traces of Hecke categories, which implies the semistable part of the Betti geometric Langlands conjecture of Ben-Zvi-Nadler in genus 1. We prove a Weyl group analogue of this conjecture. Our theorem holds in the natural generality of reflection groups in Euclidean or hyperbolic space. As a corollary, we give an expression of the centralizer of a finite order element in a reflection group using homotopy theory.
AU - Li, Penghui
ID - 6986
IS - 11
JF - Proceedings of the American Mathematical Society
SN - 0002-9939
TI - A colimit of traces of reflection groups
VL - 147
ER -
TY - CHAP
AB - Cells are arranged into species-specific patterns during early embryogenesis. Such cell division patterns are important since they often reflect the distribution of localized cortical factors from eggs/fertilized eggs to specific cells as well as the emergence of organismal form. However, it has proven difficult to reveal the mechanisms that underlie the emergence of cell positioning patterns that underlie embryonic shape, likely because a systems-level approach is required that integrates cell biological, genetic, developmental, and mechanical parameters. The choice of organism to address such questions is also important. Because ascidians display the most extreme form of invariant cleavage pattern among the metazoans, we have been analyzing the cell biological mechanisms that underpin three aspects of cell division (unequal cell division (UCD), oriented cell division (OCD), and asynchronous cell cycles) which affect the overall shape of the blastula-stage ascidian embryo composed of 64 cells. In ascidians, UCD creates two small cells at the 16-cell stage that in turn undergo two further successive rounds of UCD. Starting at the 16-cell stage, the cell cycle becomes asynchronous, whereby the vegetal half divides before the animal half, thus creating 24-, 32-, 44-, and then 64-cell stages. Perturbing either UCD or the alternate cell division rhythm perturbs cell position. We propose that dynamic cell shape changes propagate throughout the embryo via cell-cell contacts to create the ascidian-specific invariant cleavage pattern.
AU - McDougall, Alex
AU - Chenevert, Janet
AU - Godard, Benoit G
AU - Dumollard, Remi
ED - Tworzydlo, Waclaw
ED - Bilinski, Szczepan M.
ID - 6987
SN - 0080-1844
T2 - Evo-Devo: Non-model species in cell and developmental biology
TI - Emergence of embryo shape during cleavage divisions
VL - 68
ER -
TY - JOUR
AB - Platelets are central players in thrombosis and hemostasis but are increasingly recognized as key components of the immune system. They shape ensuing immune responses by recruiting leukocytes, and support the development of adaptive immunity. Recent data shed new light on the complex role of platelets in immunity. Here, we summarize experimental and clinical data on the role of platelets in host defense against bacteria. Platelets bind, contain, and kill bacteria directly; however, platelet proinflammatory effector functions and cross-talk with the coagulation system, can also result in damage to the host (e.g., acute lung injury and sepsis). Novel clinical insights support this dichotomy: platelet inhibition/thrombocytopenia can be either harmful or protective, depending on pathophysiological context. Clinical studies are currently addressing this aspect in greater depth.
AU - Nicolai, Leo
AU - Gärtner, Florian R
AU - Massberg, Steffen
ID - 6988
IS - 10
JF - Trends in Immunology
SN - 1471-4906
TI - Platelets in host defense: Experimental and clinical insights
VL - 40
ER -
TY - CONF
AB - When can a polyomino piece of paper be folded into a unit cube? Prior work studied tree-like polyominoes, but polyominoes with holes remain an intriguing open problem. We present sufficient conditions for a polyomino with hole(s) to fold into a cube, and conditions under which cube folding is impossible. In particular, we show that all but five special simple holes guarantee foldability.
AU - Aichholzer, Oswin
AU - Akitaya, Hugo A
AU - Cheung, Kenneth C
AU - Demaine, Erik D
AU - Demaine, Martin L
AU - Fekete, Sandor P
AU - Kleist, Linda
AU - Kostitsyna, Irina
AU - Löffler, Maarten
AU - Masárová, Zuzana
AU - Mundilova, Klara
AU - Schmidt, Christiane
ID - 6989
T2 - Proceedings of the 31st Canadian Conference on Computational Geometry
TI - Folding polyominoes with holes into a cube
ER -
TY - JOUR
AB - Plasmodesmata (PD) are plant-specific membrane-lined channels that create cytoplasmic and membrane continuities between adjacent cells, thereby facilitating cell–cell communication and virus movement. Plant cells have evolved diverse mechanisms to regulate PD plasticity in response to numerous environmental stimuli. In particular, during defense against plant pathogens, the defense hormone, salicylic acid (SA), plays a crucial role in the regulation of PD permeability in a callose-dependent manner. Here, we uncover a mechanism by which plants restrict the spreading of virus and PD cargoes using SA signaling by increasing lipid order and closure of PD. We showed that exogenous SA application triggered the compartmentalization of lipid raft nanodomains through a modulation of the lipid raft-regulatory protein, Remorin (REM). Genetic studies, superresolution imaging, and transmission electron microscopy observation together demonstrated that Arabidopsis REM1.2 and REM1.3 are crucial for plasma membrane nanodomain assembly to control PD aperture and functionality. In addition, we also found that a 14-3-3 epsilon protein modulates REM clustering and membrane nanodomain compartmentalization through its direct interaction with REM proteins. This study unveils a molecular mechanism by which the key plant defense hormone, SA, triggers membrane lipid nanodomain reorganization, thereby regulating PD closure to impede virus spreading.
AU - Huang, D
AU - Sun, Y
AU - Ma, Z
AU - Ke, M
AU - Cui, Y
AU - Chen, Z
AU - Chen, C
AU - Ji, C
AU - Tran, TM
AU - Yang, L
AU - Lam, SM
AU - Han, Y
AU - Shu, G
AU - Friml, Jiří
AU - Miao, Y
AU - Jiang, L
AU - Chen, X
ID - 6999
IS - 42
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
TI - Salicylic acid-mediated plasmodesmal closure via Remorin-dependent lipid organization
VL - 116
ER -
TY - JOUR
AB - The main contributions of this paper are the proposition and the convergence analysis of a class of inertial projection-type algorithm for solving variational inequality problems in real Hilbert spaces where the underline operator is monotone and uniformly continuous. We carry out a unified analysis of the proposed method under very mild assumptions. In particular, weak convergence of the generated sequence is established and nonasymptotic O(1 / n) rate of convergence is established, where n denotes the iteration counter. We also present some experimental results to illustrate the profits gained by introducing the inertial extrapolation steps.
AU - Shehu, Yekini
AU - Iyiola, Olaniyi S.
AU - Li, Xiao-Huan
AU - Dong, Qiao-Li
ID - 7000
IS - 4
JF - Computational and Applied Mathematics
SN - 2238-3603
TI - Convergence analysis of projection method for variational inequalities
VL - 38
ER -
TY - JOUR
AB - Multiple Importance Sampling (MIS) is a key technique for achieving robustness of Monte Carlo estimators in computer graphics and other fields. We derive optimal weighting functions for MIS that provably minimize the variance of an MIS estimator, given a set of sampling techniques. We show that the resulting variance reduction over the balance heuristic can be higher than predicted by the variance bounds derived by Veach and Guibas, who assumed only non-negative weights in their proof. We theoretically analyze the variance of the optimal MIS weights and show the relation to the variance of the balance heuristic. Furthermore, we establish a connection between the new weighting functions and control variates as previously applied to mixture sampling. We apply the new optimal weights to integration problems in light transport and show that they allow for new design considerations when choosing the appropriate sampling techniques for a given integration problem.
AU - Kondapaneni, Ivo
AU - Vevoda, Petr
AU - Grittmann, Pascal
AU - Skrivan, Tomas
AU - Slusallek, Philipp
AU - Křivánek, Jaroslav
ID - 7002
IS - 4
JF - ACM Transactions on Graphics
SN - 0730-0301
TI - Optimal multiple importance sampling
VL - 38
ER -
TY - JOUR
AB - Activity-dependent bulk endocytosis generates synaptic vesicles (SVs) during intense neuronal activity via a two-step process. First, bulk endosomes are formed direct from the plasma membrane from which SVs are then generated. SV generation from bulk endosomes requires the efflux of previously accumulated calcium and activation of the protein phosphatase calcineurin. However, it is still unknown how calcineurin mediates SV generation. We addressed this question using a series of acute interventions that decoupled the generation of SVs from bulk endosomes in rat primary neuronal culture. This was achieved by either disruption of protein–protein interactions via delivery of competitive peptides, or inhibition of enzyme activity by known inhibitors. SV generation was monitored using either a morphological horseradish peroxidase assay or an optical assay that monitors the replenishment of the reserve SV pool. We found that SV generation was inhibited by, (i) peptides that disrupt calcineurin interactions, (ii) an inhibitor of dynamin I GTPase activity and (iii) peptides that disrupt the phosphorylation-dependent dynamin I–syndapin I interaction. Peptides that disrupted syndapin I interactions with eps15 homology domain-containing proteins had no effect. This revealed that (i) calcineurin must be localized at bulk endosomes to mediate its effect, (ii) dynamin I GTPase activity is essential for SV fission and (iii) the calcineurin-dependent interaction between dynamin I and syndapin I is essential for SV generation. We therefore propose that a calcineurin-dependent dephosphorylation cascade that requires both dynamin I GTPase and syndapin I lipid-deforming activity is essential for SV generation from bulk endosomes.
AU - Cheung, Giselle T
AU - Cousin, Michael A.
ID - 7005
IS - 5
JF - Journal of Neurochemistry
SN - 0022-3042
TI - Synaptic vesicle generation from activity‐dependent bulk endosomes requires a dephosphorylation‐dependent dynamin–syndapin interaction
VL - 151
ER -
TY - JOUR
AB - We consider the primitive relay channel, where the source sends a message to the relay and to the destination, and the relay helps the communication by transmitting an additional message to the destination via a separate channel. Two well-known coding techniques have been introduced for this setting: decode-and-forward and compress-and-forward. In decode-and-forward, the relay completely decodes the message and sends some information to the destination; in compress-and-forward, the relay does not decode, and it sends a compressed version of the received signal to the destination using Wyner–Ziv coding. In this paper, we present a novel coding paradigm that provides an improved achievable rate for the primitive relay channel. The idea is to combine compress-and-forward and decode-and-forward via a chaining construction. We transmit over pairs of blocks: in the first block, we use compress-and-forward; and, in the second block, we use decode-and-forward. More specifically, in the first block, the relay does not decode, it compresses the received signal via Wyner–Ziv, and it sends only part of the compression to the destination. In the second block, the relay completely decodes the message, it sends some information to the destination, and it also sends the remaining part of the compression coming from the first block. By doing so, we are able to strictly outperform both compress-and-forward and decode-and-forward. Note that the proposed coding scheme can be implemented with polar codes. As such, it has the typical attractive properties of polar coding schemes, namely, quasi-linear encoding and decoding complexity, and error probability that decays at super-polynomial speed. As a running example, we take into account the special case of the erasure relay channel, and we provide a comparison between the rates achievable by our proposed scheme and the existing upper and lower bounds.
AU - Mondelli, Marco
AU - Hassani, S. Hamed
AU - Urbanke, Rüdiger
ID - 7007
IS - 10
JF - Algorithms
SN - 1999-4893
TI - A new coding paradigm for the primitive relay channel
VL - 12
ER -
TY - JOUR
AB - Cell migration is essential for physiological processes as diverse as development, immune defence and wound healing. It is also a hallmark of cancer malignancy. Thousands of publications have elucidated detailed molecular and biophysical mechanisms of cultured cells migrating on flat, 2D substrates of glass and plastic. However, much less is known about how cells successfully navigate the complex 3D environments of living tissues. In these more complex, native environments, cells use multiple modes of migration, including mesenchymal, amoeboid, lobopodial and collective, and these are governed by the local extracellular microenvironment, specific modalities of Rho GTPase signalling and non- muscle myosin contractility. Migration through 3D environments is challenging because it requires the cell to squeeze through complex or dense extracellular structures. Doing so requires specific cellular adaptations to mechanical features of the extracellular matrix (ECM) or its remodelling. In addition, besides navigating through diverse ECM environments and overcoming extracellular barriers, cells often interact with neighbouring cells and tissues through physical and signalling interactions. Accordingly, cells need to call on an impressively wide diversity of mechanisms to meet these challenges. This Review examines how cells use both classical and novel mechanisms of locomotion as they traverse challenging 3D matrices and cellular environments. It focuses on principles rather than details of migratory mechanisms and draws comparisons between 1D, 2D and 3D migration.
AU - Yamada, KM
AU - Sixt, Michael K
ID - 7009
IS - 12
JF - Nature Reviews Molecular Cell Biology
SN - 1471-0072
TI - Mechanisms of 3D cell migration
VL - 20
ER -
TY - CONF
AB - Numerous biophysical questions require the quantification of short-range interactions between (functionalized) surfaces and synthetic or biological objects such as cells. Here, we present an original, custom built setup for reflection interference contrast microscopy that can assess distances between a substrate and a flowing object at high speed with nanometric accuracy. We demonstrate its use to decipher the complex biochemical and mechanical interplay regulating blood cell homing at the vessel wall in the microcirculation using an in vitro approach. We show that in the absence of specific biochemical interactions, flowing cells are repelled from the soft layer lining the vessel wall, contributing to red blood cell repulsion in vivo. In contrast, this so-called glycocalyx stabilizes rolling of cells under flow in the presence of a specific receptor naturally present on activated leucocytes and a number of cancer cell lines.
AU - Davies, Heather S.
AU - Baranova, Natalia S.
AU - El Amri, Nouha
AU - Coche-Guérente, Liliane
AU - Verdier, Claude
AU - Bureau, Lionel
AU - Richter, Ralf P.
AU - Débarre, Delphine
ID - 7010
SN - 1605-7422
T2 - Advances in Microscopic Imaging II
TI - Blood cell-vessel wall interactions probed by reflection interference contrast microscopy
VL - 11076
ER -
TY - JOUR
AB - Chains of superconducting circuit devices provide a natural platform for studies of synthetic bosonic quantum matter. Motivated by the recent experimental progress in realizing disordered and interacting chains of superconducting transmon devices, we study the bosonic many-body localization phase transition using the methods of exact diagonalization as well as matrix product state dynamics. We estimate the location of transition separating the ergodic and the many-body localized phases as a function of the disorder strength and the many-body on-site interaction strength. The main difference between the bosonic model realized by superconducting circuits and similar fermionic model is that the effect of the on-site interaction is stronger due to the possibility of multiple excitations occupying the same site. The phase transition is found to be robust upon including longer-range hopping and interaction terms present in the experiments. Furthermore, we calculate experimentally relevant local observables and show that their temporal fluctuations can be used to distinguish between the dynamics of Anderson insulator, many-body localization, and delocalized phases. While we consider unitary dynamics, neglecting the effects of dissipation, decoherence, and measurement back action, the timescales on which the dynamics is unitary are sufficient for observation of characteristic dynamics in the many-body localized phase. Moreover, the experimentally available disorder strength and interactions allow for tuning the many-body localization phase transition, thus making the arrays of superconducting circuit devices a promising platform for exploring localization physics and phase transition.
AU - Orell, Tuure
AU - Michailidis, Alexios
AU - Serbyn, Maksym
AU - Silveri, Matti
ID - 7013
IS - 13
JF - Physical Review B
SN - 2469-9950
TI - Probing the many-body localization phase transition with superconducting circuits
VL - 100
ER -
TY - JOUR
AB - We modify the "floating crystal" trial state for the classical homogeneous electron gas (also known as jellium), in order to suppress the boundary charge fluctuations that are known to lead to a macroscopic increase of the energy. The argument is to melt a thin layer of the crystal close to the boundary and consequently replace it by an incompressible fluid. With the aid of this trial state we show that three different definitions of the ground-state energy of jellium coincide. In the first point of view the electrons are placed in a neutralizing uniform background. In the second definition there is no background but the electrons are submitted to the constraint that their density is constant, as is appropriate in density functional theory. Finally, in the third system each electron interacts with a periodic image of itself; that is, periodic boundary conditions are imposed on the interaction potential.
AU - Lewin, Mathieu
AU - Lieb, Elliott H.
AU - Seiringer, Robert
ID - 7015
IS - 3
JF - Physical Review B
SN - 2469-9950
TI - Floating Wigner crystal with no boundary charge fluctuations
VL - 100
ER -
TY - DATA
AB - Organisms cope with change by employing transcriptional regulators. However, when faced with rare environments, the evolution of transcriptional regulators and their promoters may be too slow. We ask whether the intrinsic instability of gene duplication and amplification provides a generic alternative to canonical gene regulation. By real-time monitoring of gene copy number mutations in E. coli, we show that gene duplications and amplifications enable adaptation to fluctuating environments by rapidly generating copy number, and hence expression level, polymorphism. This ‘amplification-mediated gene expression tuning’ occurs on timescales similar to canonical gene regulation and can deal with rapid environmental changes. Mathematical modeling shows that amplifications also tune gene expression in stochastic environments where transcription factor-based schemes are hard to evolve or maintain. The fleeting nature of gene amplifications gives rise to a generic population-level mechanism that relies on genetic heterogeneity to rapidly tune expression of any gene, without leaving any genomic signature.
AU - Tomanek, Isabella
ID - 7016
KW - Escherichia coli
KW - gene amplification
KW - galactose
KW - DOG
KW - experimental evolution
KW - Illumina sequence data
KW - FACS data
KW - microfluidics data
TI - Data for the paper "Gene amplification as a form of population-level gene expression regulation"
ER -
TY - JOUR
AB - Effective design of combination therapies requires understanding the changes in cell physiology that result from drug interactions. Here, we show that the genome-wide transcriptional response to combinations of two drugs, measured at a rigorously controlled growth rate, can predict higher-order antagonism with a third drug in Saccharomyces cerevisiae. Using isogrowth profiling, over 90% of the variation in cellular response can be decomposed into three principal components (PCs) that have clear biological interpretations. We demonstrate that the third PC captures emergent transcriptional programs that are dependent on both drugs and can predict antagonism with a third drug targeting the emergent pathway. We further show that emergent gene expression patterns are most pronounced at a drug ratio where the drug interaction is strongest, providing a guideline for future measurements. Our results provide a readily applicable recipe for uncovering emergent responses in other systems and for higher-order drug combinations. A record of this paper’s transparent peer review process is included in the Supplemental Information.
AU - Lukacisin, Martin
AU - Bollenbach, Tobias
ID - 7026
IS - 5
JF - Cell Systems
SN - 2405-4712
TI - Emergent gene expression responses to drug combinations predict higher-order drug interactions
VL - 9
ER -
TY - CONF
AB - Optical frequency combs (OFCs) are light sources whose spectra consists of equally spaced frequency lines in the optical domain [1]. They have great potential for improving high-capacity data transfer, all-optical atomic clocks, spectroscopy, and high-precision measurements [2].
AU - Rueda Sanchez, Alfredo R
AU - Sedlmeir, Florian
AU - Leuchs, Gerd
AU - Kuamri, Madhuri
AU - Schwefel, Harald G. L.
ID - 7032
SN - 9781728104690
T2 - 2019 Conference on Lasers and Electro-Optics Europe & European Quantum Electronics Conference
TI - Electro-optic frequency comb generation in lithium niobate whispering gallery mode resonators
ER -
TY - JOUR
AB - We find a graph of genus 5 and its drawing on the orientable surface of genus 4 with every pair of independent edges crossing an even number of times. This shows that the strong Hanani–Tutte theorem cannot be extended to the orientable surface of genus 4. As a base step in the construction we use a counterexample to an extension of the unified Hanani–Tutte theorem on the torus.
AU - Fulek, Radoslav
AU - Kynčl, Jan
ID - 7034
IS - 6
JF - Combinatorica
SN - 0209-9683
TI - Counterexample to an extension of the Hanani-Tutte theorem on the surface of genus 4
VL - 39
ER -
TY - CONF
AB - The aim of this short note is to expound one particular issue that was discussed during the talk [10] given at the symposium ”Researches on isometries as preserver problems and related topics” at Kyoto RIMS. That is, the role of Dirac masses by describing the isometry group of various metric spaces of probability measures. This article is of survey character, and it does not contain any essentially new results.From an isometric point of view, in some cases, metric spaces of measures are similar to C(K)-type function spaces. Similarity means here that their isometries are driven by some nice transformations of the underlying space. Of course, it depends on the particular choice of the metric how nice these transformations should be. Sometimes, as we will see, being a homeomorphism is enough to generate an isometry. But sometimes we need more: the transformation must preserve the underlying distance as well. Statements claiming that isometries in questions are necessarily induced by homeomorphisms are called Banach-Stone-type results, while results asserting that the underlying transformation is necessarily an isometry are termed as isometric rigidity results.As Dirac masses can be considered as building bricks of the set of all Borel measures, a natural question arises:Is it enough to understand how an isometry acts on the set of Dirac masses? Does this action extend uniquely to all measures?In what follows, we will thoroughly investigate this question.
AU - Geher, Gyorgy Pal
AU - Titkos, Tamas
AU - Virosztek, Daniel
ID - 7035
T2 - Kyoto RIMS Kôkyûroku
TI - Dirac masses and isometric rigidity
VL - 2125
ER -
TY - JOUR
AB - A recent class of topological nodal-line semimetals with the general formula MSiX (M = Zr, Hf and X = S, Se, Te) has attracted much experimental and theoretical interest due to their properties, particularly their large magnetoresistances and high carrier mobilities. The plateletlike nature of the MSiX crystals and their extremely low residual resistivities make measurements of the resistivity along the [001] direction extremely challenging. To accomplish such measurements, microstructures of single crystals were prepared using focused ion beam techniques. Microstructures prepared in this manner have very well-defined geometries and maintain their high crystal quality, verified by the observations of quantum oscillations. We present magnetoresistance and quantum oscillation data for currents applied along both [001] and [100] in ZrSiS and ZrSiSe, which are consistent with the nontrivial topology of the Dirac line-node, as determined by a measured π Berry phase. Surprisingly, we find that, despite the three dimensional nature of both the Fermi surfaces of ZrSiS and ZrSiSe, both the resistivity anisotropy under applied magnetic fields and the in-plane angular dependent magnetoresistance differ considerably between the two compounds. Finally, we discuss the role microstructuring can play in the study of these materials and our ability to make these microstructures free-standing.
AU - Shirer, Kent R.
AU - Modic, Kimberly A
AU - Zimmerling, Tino
AU - Bachmann, Maja D.
AU - König, Markus
AU - Moll, Philip J. W.
AU - Schoop, Leslie
AU - Mackenzie, Andrew P.
ID - 7055
IS - 10
JF - APL Materials
SN - 2166-532X
TI - Out-of-plane transport in ZrSiS and ZrSiSe microstructures
VL - 7
ER -
TY - JOUR
AB - In the Ca1−x La x FeAs2 (1 1 2) family of pnictide superconductors, we have investigated a highly overdoped composition (x = 0.56), prepared by a high-pressure, high-temperature synthesis. Magnetic measurements show an antiferromagnetic transition at T N = 120 K, well above the one at lower doping (0.15 < x < 0.27).
Below the onset of long-range magnetic order at T N, the electrical resistivity is strongly reduced and is dominated by electron–electron interactions, as evident from its temperature dependence. The Seebeck coefficient shows a clear metallic behavior as in narrow band conductors. The temperature dependence of the Hall coefficient and the violation of Kohler's rule agree with the multiband character of the material. No superconductivity was observed down to 1.8 K. The success of the high-pressure synthesis encourages further investigations of the so far only partially explored phase diagram in this family of Iron-based high temperature superconductors.
AU - Martino, Edoardo
AU - Bachmann, Maja D
AU - Rossi, Lidia
AU - Modic, Kimberly A
AU - Zivkovic, Ivica
AU - Rønnow, Henrik M
AU - Moll, Philip J W
AU - Akrap, Ana
AU - Forró, László
AU - Katrych, Sergiy
ID - 7056
IS - 48
JF - Journal of Physics: Condensed Matter
SN - 0953-8984
TI - Persistent antiferromagnetic order in heavily overdoped Ca1−x La x FeAs2
VL - 31
ER -
TY - JOUR
AB - We present a high magnetic field study of NbP—a member of the monopnictide Weyl semimetal (WSM) family. While the monoarsenides (NbAs and TaAs) have topologically distinct left and right-handed Weyl fermi surfaces, NbP is argued to be “topologically trivial” due to the fact that all pairs of Weyl nodes are encompassed by a single Fermi surface. We use torque magnetometry to measure the magnetic response of NbP up to 60 tesla and uncover a Berry paramagnetic response, characteristic of the topological Weyl nodes, across the entire field range. At the quantum limit B* (≈32 T), τ/B experiences a change in slope when the chemical potential enters the last Landau level. Our calculations confirm that this magnetic response arises from band topology of the Weyl pocket, even though the Fermi surface encompasses both Weyl nodes at zero magnetic field. We also find that the magnetic field pulls the chemical potential to the chiral n = 0 Landau level in the quantum limit, providing a disorder-free way of accessing chiral Weyl fermions in systems that are “not quite” WSMs in zero magnetic field.
AU - Modic, Kimberly A
AU - Meng, Tobias
AU - Ronning, Filip
AU - Bauer, Eric D.
AU - Moll, Philip J. W.
AU - Ramshaw, B. J.
ID - 7057
IS - 1
JF - Scientific Reports
SN - 2045-2322
TI - Thermodynamic signatures of Weyl fermions in NbP
VL - 9
ER -
TY - JOUR
AB - Although crystals of strongly correlated metals exhibit a diverse set of electronic ground states, few approaches exist for spatially modulating their properties. In this study, we demonstrate disorder-free control, on the micrometer scale, over the superconducting state in samples of the heavy-fermion superconductor CeIrIn5. We pattern crystals by focused ion beam milling to tailor the boundary conditions for the elastic deformation upon thermal contraction during cooling. The resulting nonuniform strain fields induce complex patterns of superconductivity, owing to the strong dependence of the transition temperature on the strength and direction of strain. These results showcase a generic approach to manipulating electronic order on micrometer length scales in strongly correlated matter without compromising the cleanliness, stoichiometry, or mean free path.
AU - Bachmann, Maja D.
AU - Ferguson, G. M.
AU - Theuss, Florian
AU - Meng, Tobias
AU - Putzke, Carsten
AU - Helm, Toni
AU - Shirer, K. R.
AU - Li, You-Sheng
AU - Modic, Kimberly A
AU - Nicklas, Michael
AU - König, Markus
AU - Low, D.
AU - Ghosh, Sayak
AU - Mackenzie, Andrew P.
AU - Arnold, Frank
AU - Hassinger, Elena
AU - McDonald, Ross D.
AU - Winter, Laurel E.
AU - Bauer, Eric D.
AU - Ronning, Filip
AU - Ramshaw, B. J.
AU - Nowack, Katja C.
AU - Moll, Philip J. W.
ID - 7082
IS - 6462
JF - Science
SN - 0036-8075
TI - Spatial control of heavy-fermion superconductivity in CeIrIn5
VL - 366
ER -
TY - JOUR
AB - In graph theory, as well as in 3-manifold topology, there exist several width-type parameters to describe how "simple" or "thin" a given graph or 3-manifold is. These parameters, such as pathwidth or treewidth for graphs, or the concept of thin position for 3-manifolds, play an important role when studying algorithmic problems; in particular, there is a variety of problems in computational 3-manifold topology - some of them known to be computationally hard in general - that become solvable in polynomial time as soon as the dual graph of the input triangulation has bounded treewidth.
In view of these algorithmic results, it is natural to ask whether every 3-manifold admits a triangulation of bounded treewidth. We show that this is not the case, i.e., that there exists an infinite family of closed 3-manifolds not admitting triangulations of bounded pathwidth or treewidth (the latter implies the former, but we present two separate proofs).
We derive these results from work of Agol, of Scharlemann and Thompson, and of Scharlemann, Schultens and Saito by exhibiting explicit connections between the topology of a 3-manifold M on the one hand and width-type parameters of the dual graphs of triangulations of M on the other hand, answering a question that had been raised repeatedly by researchers in computational 3-manifold topology. In particular, we show that if a closed, orientable, irreducible, non-Haken 3-manifold M has a triangulation of treewidth (resp. pathwidth) k then the Heegaard genus of M is at most 18(k+1) (resp. 4(3k+1)).
AU - Huszár, Kristóf
AU - Spreer, Jonathan
AU - Wagner, Uli
ID - 7093
IS - 2
JF - Journal of Computational Geometry
SN - 1920-180X
TI - On the treewidth of triangulated 3-manifolds
VL - 10
ER -
TY - JOUR
AB - BAX, a member of the BCL2 gene family, controls the committed step of the intrinsic apoptotic program. Mitochondrial fragmentation is a commonly observed feature of apoptosis, which occurs through the process of mitochondrial fission. BAX has consistently been associated with mitochondrial fission, yet how BAX participates in the process of mitochondrial fragmentation during apoptosis remains to be tested. Time-lapse imaging of BAX recruitment and mitochondrial fragmentation demonstrates that rapid mitochondrial fragmentation during apoptosis occurs after the complete recruitment of BAX to the mitochondrial outer membrane (MOM). The requirement of a fully functioning BAX protein for the fission process was demonstrated further in BAX/BAK-deficient HCT116 cells expressing a P168A mutant of BAX. The mutant performed fusion to restore the mitochondrial network. but was not demonstrably recruited to the MOM after apoptosis induction. Under these conditions, mitochondrial fragmentation was blocked. Additionally, we show that loss of the fission protein, dynamin-like protein 1 (DRP1), does not temporally affect the initiation time or rate of BAX recruitment, but does reduce the final level of BAX recruited to the MOM during the late phase of BAX recruitment. These correlative observations suggest a model where late-stage BAX oligomers play a functional part of the mitochondrial fragmentation machinery in apoptotic cells.
AU - Maes, Margaret E
AU - Grosser, J. A.
AU - Fehrman, R. L.
AU - Schlamp, C. L.
AU - Nickells, R. W.
ID - 7095
JF - Scientific Reports
TI - Completion of BAX recruitment correlates with mitochondrial fission during apoptosis
VL - 9
ER -
TY - JOUR
AB - Early endosomes, also called sorting endosomes, are known to mature into late endosomesvia the Rab5-mediated endolysosomal trafficking pathway. Thus, early endosome existence isthought to be maintained by the continual fusion of transport vesicles from the plasmamembrane and thetrans-Golgi network (TGN). Here we show instead that endocytosis isdispensable and post-Golgi vesicle transport is crucial for the formation of endosomes andthe subsequent endolysosomal traffic regulated by yeast Rab5 Vps21p. Fittingly, all threeproteins required for endosomal nucleotide exchange on Vps21p arefirst recruited to theTGN before transport to the endosome, namely the GEF Vps9p and the epsin-relatedadaptors Ent3/5p. The TGN recruitment of these components is distinctly controlled, withVps9p appearing to require the Arf1p GTPase, and the Rab11s, Ypt31p/32p. These resultsprovide a different view of endosome formation and identify the TGN as a critical location forregulating progress through the endolysosomal trafficking pathway.
AU - Nagano, Makoto
AU - Toshima, Junko Y.
AU - Siekhaus, Daria E
AU - Toshima, Jiro
ID - 7097
IS - 1
JF - Communications Biology
SN - 2399-3642
TI - Rab5-mediated endosome formation is regulated at the trans-Golgi network
VL - 2
ER -
TY - JOUR
AU - Kasugai, Yu
AU - Vogel, Elisabeth
AU - Hörtnagl, Heide
AU - Schönherr, Sabine
AU - Paradiso, Enrica
AU - Hauschild, Markus
AU - Göbel, Georg
AU - Milenkovic, Ivan
AU - Peterschmitt, Yvan
AU - Tasan, Ramon
AU - Sperk, Günther
AU - Shigemoto, Ryuichi
AU - Sieghart, Werner
AU - Singewald, Nicolas
AU - Lüthi, Andreas
AU - Ferraguti, Francesco
ID - 7099
IS - 4
JF - Neuron
SN - 0896-6273
TI - Structural and functional remodeling of amygdala GABAergic synapses in associative fear learning
VL - 104
ER -
TY - JOUR
AB - We present microscopic derivations of the defocusing two-dimensional cubic nonlinear Schrödinger equation and the Gross–Pitaevskii equation starting froman interacting N-particle system of bosons. We consider the interaction potential to be given either by Wβ(x)=N−1+2βW(Nβx), for any β>0, or to be given by VN(x)=e2NV(eNx), for some spherical symmetric, nonnegative and compactly supported W,V∈L∞(R2,R). In both cases we prove the convergence of the reduced density corresponding to the exact time evolution to the projector onto the solution of the corresponding nonlinear Schrödinger equation in trace norm. For the latter potential VN we show that it is crucial to take the microscopic structure of the condensate into account in order to obtain the correct dynamics.
AU - Jeblick, Maximilian
AU - Leopold, Nikolai K
AU - Pickl, Peter
ID - 7100
IS - 1
JF - Communications in Mathematical Physics
SN - 0010-3616
TI - Derivation of the time dependent Gross–Pitaevskii equation in two dimensions
VL - 372
ER -
TY - JOUR
AB - Origin and functions of intermittent transitions among sleep stages, including short awakenings and arousals, constitute a challenge to the current homeostatic framework for sleep regulation, focusing on factors modulating sleep over large time scales. Here we propose that the complex micro-architecture characterizing the sleep-wake cycle results from an underlying non-equilibrium critical dynamics, bridging collective behaviors across spatio-temporal scales. We investigate θ and δ wave dynamics in control rats and in rats with lesions of sleep-promoting neurons in the parafacial zone. We demonstrate that intermittent bursts in θ and δ rhythms exhibit a complex temporal organization, with long-range power-law correlations and a robust duality of power law (θ-bursts, active phase) and exponential-like (δ-bursts, quiescent phase) duration distributions, typical features of non-equilibrium systems self-organizing at criticality. Crucially, such temporal organization relates to anti-correlated coupling between θ- and δ-bursts, and is independent of the dominant physiologic state and lesions, a solid indication of a basic principle in sleep dynamics.
AU - Wang, Jilin W. J. L.
AU - Lombardi, Fabrizio
AU - Zhang, Xiyun
AU - Anaclet, Christelle
AU - Ivanov, Plamen Ch.
ID - 7103
IS - 11
JF - PLOS Computational Biology
SN - 1553-7358
TI - Non-equilibrium critical dynamics of bursts in θ and δ rhythms as fundamental characteristic of sleep and wake micro-architecture
VL - 15
ER -
TY - JOUR
AB - Cell migration is hypothesized to involve a cycle of behaviours beginning with leading edge extension. However, recent evidence suggests that the leading edge may be dispensable for migration, raising the question of what actually controls cell directionality. Here, we exploit the embryonic migration of Drosophila macrophages to bridge the different temporal scales of the behaviours controlling motility. This approach reveals that edge fluctuations during random motility are not persistent and are weakly correlated with motion. In contrast, flow of the actin network behind the leading edge is highly persistent. Quantification of actin flow structure during migration reveals a stable organization and asymmetry in the cell-wide flowfield that strongly correlates with cell directionality. This organization is regulated by a gradient of actin network compression and destruction, which is controlled by myosin contraction and cofilin-mediated disassembly. It is this stable actin-flow polarity, which integrates rapid fluctuations of the leading edge, that controls inherent cellular persistence.
AU - Yolland, Lawrence
AU - Burki, Mubarik
AU - Marcotti, Stefania
AU - Luchici, Andrei
AU - Kenny, Fiona N.
AU - Davis, John Robert
AU - Serna-Morales, Eduardo
AU - Müller, Jan
AU - Sixt, Michael K
AU - Davidson, Andrew
AU - Wood, Will
AU - Schumacher, Linus J.
AU - Endres, Robert G.
AU - Miodownik, Mark
AU - Stramer, Brian M.
ID - 7105
IS - 11
JF - Nature Cell Biology
SN - 1465-7392
TI - Persistent and polarized global actin flow is essential for directionality during cell migration
VL - 21
ER -
TY - JOUR
AB - PIN-FORMED (PIN) transporters mediate directional, intercellular movement of the phytohormone auxin in land plants. To elucidate the evolutionary origins of this developmentally crucial mechanism, we analysed the single PIN homologue of a simple green alga Klebsormidium flaccidum. KfPIN functions as a plasma membrane-localized auxin exporter in land plants and heterologous models. While its role in algae remains unclear, PIN-driven auxin export is probably an ancient and conserved trait within streptophytes.
AU - Skokan, Roman
AU - Medvecká, Eva
AU - Viaene, Tom
AU - Vosolsobě, Stanislav
AU - Zwiewka, Marta
AU - Müller, Karel
AU - Skůpa, Petr
AU - Karady, Michal
AU - Zhang, Yuzhou
AU - Janacek, Dorina P.
AU - Hammes, Ulrich Z.
AU - Ljung, Karin
AU - Nodzyński, Tomasz
AU - Petrášek, Jan
AU - Friml, Jiří
ID - 7106
IS - 11
JF - Nature Plants
SN - 2055-0278
TI - PIN-driven auxin transport emerged early in streptophyte evolution
VL - 5
ER -
TY - JOUR
AB - We prove that for every d ≥ 2, deciding if a pure, d-dimensional, simplicial complex is shellable is NP-hard, hence NP-complete. This resolves a question raised, e.g., by Danaraj and Klee in 1978. Our reduction also yields that for every d ≥ 2 and k ≥ 0, deciding if a pure, d-dimensional, simplicial complex is k-decomposable is NP-hard. For d ≥ 3, both problems remain NP-hard when restricted to contractible pure d-dimensional complexes. Another simple corollary of our result is that it is NP-hard to decide whether a given poset is CL-shellable.
AU - Goaoc, Xavier
AU - Patak, Pavel
AU - Patakova, Zuzana
AU - Tancer, Martin
AU - Wagner, Uli
ID - 7108
IS - 3
JF - Journal of the ACM
SN - 0004-5411
TI - Shellability is NP-complete
VL - 66
ER -
TY - JOUR
AB - We show how to construct temporal testers for the logic MITL, a prominent linear-time logic for real-time systems. A temporal tester is a transducer that inputs a signal holding the Boolean value of atomic propositions and outputs the truth value of a formula along time. Here we consider testers over continuous-time Boolean signals that use clock variables to enforce duration constraints, as in timed automata. We first rewrite the MITL formula into a “simple” formula using a limited set of temporal modalities. We then build testers for these specific modalities and show how to compose testers for simple formulae into complex ones. Temporal testers can be turned into acceptors, yielding a compositional translation from MITL to timed automata. This construction is much simpler than previously known and remains asymptotically optimal. It supports both past and future operators and can easily be extended.
AU - Ferrere, Thomas
AU - Maler, Oded
AU - Ničković, Dejan
AU - Pnueli, Amir
ID - 7109
IS - 3
JF - Journal of the ACM
SN - 0004-5411
TI - From real-time logic to timed automata
VL - 66
ER -
TY - JOUR
AB - We propose a novel generic shape optimization method for CAD models based on the eXtended Finite Element Method (XFEM). Our method works directly on the intersection between the model and a regular simulation grid, without the need to mesh or remesh, thus removing a bottleneck of classical shape optimization strategies. This is made possible by a novel hierarchical integration scheme that accurately integrates finite element quantities with sub-element precision. For optimization, we efficiently compute analytical shape derivatives of the entire framework, from model intersection to integration rule generation and XFEM simulation. Moreover, we describe a differentiable projection of shape parameters onto a constraint manifold spanned by user-specified shape preservation, consistency, and manufacturability constraints. We demonstrate the utility of our approach by optimizing mass distribution, strength-to-weight ratio, and inverse elastic shape design objectives directly on parameterized 3D CAD models.
AU - Hafner, Christian
AU - Schumacher, Christian
AU - Knoop, Espen
AU - Auzinger, Thomas
AU - Bickel, Bernd
AU - Bächer, Moritz
ID - 7117
IS - 6
JF - ACM Transactions on Graphics
SN - 0730-0301
TI - X-CAD: Optimizing CAD Models with Extended Finite Elements
VL - 38
ER -
TY - CONF
AB - Data-rich applications in machine-learning and control have motivated an intense research on large-scale optimization. Novel algorithms have been proposed and shown to have optimal convergence rates in terms of iteration counts. However, their practical performance is severely degraded by the cost of exchanging high-dimensional gradient vectors between computing nodes. Several gradient compression heuristics have recently been proposed to reduce communications, but few theoretical results exist that quantify how they impact algorithm convergence. This paper establishes and strengthens the convergence guarantees for gradient descent under a family of gradient compression techniques. For convex optimization problems, we derive admissible step sizes and quantify both the number of iterations and the number of bits that need to be exchanged to reach a target accuracy. Finally, we validate the performance of different gradient compression techniques in simulations. The numerical results highlight the properties of different gradient compression algorithms and confirm that fast convergence with limited information exchange is possible.
AU - Khirirat, Sarit
AU - Johansson, Mikael
AU - Alistarh, Dan-Adrian
ID - 7122
SN - 0743-1546
T2 - 2018 IEEE Conference on Decision and Control
TI - Gradient compression for communication-limited convex optimization
ER -
TY - JOUR
AB - Loss of functional cardiomyocytes is a major determinant of heart failure after myocardial infarction. Previous high throughput screening studies have identified a few microRNAs (miRNAs) that can induce cardiomyocyte proliferation and stimulate cardiac regeneration in mice. Here, we show that all of the most effective of these miRNAs activate nuclear localization of the master transcriptional cofactor Yes-associated protein (YAP) and induce expression of YAP-responsive genes. In particular, miR-199a-3p directly targets two mRNAs coding for proteins impinging on the Hippo pathway, the upstream YAP inhibitory kinase TAOK1, and the E3 ubiquitin ligase β-TrCP, which leads to YAP degradation. Several of the pro-proliferative miRNAs (including miR-199a-3p) also inhibit filamentous actin depolymerization by targeting Cofilin2, a process that by itself activates YAP nuclear translocation. Thus, activation of YAP and modulation of the actin cytoskeleton are major components of the pro-proliferative action of miR-199a-3p and other miRNAs that induce cardiomyocyte proliferation.
AU - Torrini, Consuelo
AU - Cubero, Ryan J
AU - Dirkx, Ellen
AU - Braga, Luca
AU - Ali, Hashim
AU - Prosdocimo, Giulia
AU - Gutierrez, Maria Ines
AU - Collesi, Chiara
AU - Licastro, Danilo
AU - Zentilin, Lorena
AU - Mano, Miguel
AU - Zacchigna, Serena
AU - Vendruscolo, Michele
AU - Marsili, Matteo
AU - Samal, Areejit
AU - Giacca, Mauro
ID - 7128
IS - 9
JF - Cell Reports
KW - cardiomyocyte
KW - cell cycle
KW - Cofilin2
KW - cytoskeleton
KW - Hippo
KW - microRNA
KW - regeneration
KW - YAP
SN - 2211-1247
TI - Common regulatory pathways mediate activity of microRNAs inducing cardiomyocyte proliferation
VL - 27
ER -
TY - JOUR
AB - We show that statistical criticality, i.e. the occurrence of power law frequency distributions, arises in samples that are maximally informative about the underlying generating process. In order to reach this conclusion, we first identify the frequency with which different outcomes occur in a sample, as the variable carrying useful information on the generative process. The entropy of the frequency, that we call relevance, provides an upper bound to the number of informative bits. This differs from the entropy of the data, that we take as a measure of resolution. Samples that maximise relevance at a given resolution—that we call maximally informative samples—exhibit statistical criticality. In particular, Zipf's law arises at the optimal trade-off between resolution (i.e. compression) and relevance. As a byproduct, we derive a bound of the maximal number of parameters that can be estimated from a dataset, in the absence of prior knowledge on the generative model.
Furthermore, we relate criticality to the statistical properties of the representation of the data generating process. We show that, as a consequence of the concentration property of the asymptotic equipartition property, representations that are maximally informative about the data generating process are characterised by an exponential distribution of energy levels. This arises from a principle of minimal entropy, that is conjugate of the maximum entropy principle in statistical mechanics. This explains why statistical criticality requires no parameter fine tuning in maximally informative samples.
AU - Cubero, Ryan J
AU - Jo, Junghyo
AU - Marsili, Matteo
AU - Roudi, Yasser
AU - Song, Juyong
ID - 7130
IS - 6
JF - Journal of Statistical Mechanics: Theory and Experiment
KW - optimization under uncertainty
KW - source coding
KW - large deviation
SN - 1742-5468
TI - Statistical criticality arises in most informative representations
VL - 2019
ER -
TY - CONF
AB - It is well established that the notion of min-entropy fails to satisfy the \emph{chain rule} of the form H(X,Y)=H(X|Y)+H(Y), known for Shannon Entropy. Such a property would help to analyze how min-entropy is split among smaller blocks. Problems of this kind arise for example when constructing extractors and dispersers.
We show that any sequence of variables exhibits a very strong strong block-source structure (conditional distributions of blocks are nearly flat) when we \emph{spoil few correlated bits}. This implies, conditioned on the spoiled bits, that \emph{splitting-recombination properties} hold. In particular, we have many nice properties that min-entropy doesn't obey in general, for example strong chain rules, "information can't hurt" inequalities, equivalences of average and worst-case conditional entropy definitions and others. Quantitatively, for any sequence X1,…,Xt of random variables over an alphabet X we prove that, when conditioned on m=t⋅O(loglog|X|+loglog(1/ϵ)+logt) bits of auxiliary information, all conditional distributions of the form Xi|X