TY - JOUR
AB - We introduce a modification of the classic notion of intrinsic volume using persistence moments of height functions. Evaluating the modified first intrinsic volume on digital approximations of a compact body with smoothly embedded boundary in Rn, we prove convergence to the first intrinsic volume of the body as the resolution of the approximation improves. We have weaker results for the other modified intrinsic volumes, proving they converge to the corresponding intrinsic volumes of the n-dimensional unit ball.
AU - Edelsbrunner, Herbert
AU - Pausinger, Florian
ID - 1662
JF - Advances in Mathematics
TI - Approximation and convergence of the intrinsic volume
VL - 287
ER -
TY - JOUR
AB - We introduce a scheme for preparation, manipulation, and read out of Majorana zero modes in semiconducting wires with mesoscopic superconducting islands. Our approach synthesizes recent advances in materials growth with tools commonly used in quantum-dot experiments, including gate control of tunnel barriers and Coulomb effects, charge sensing, and charge pumping. We outline a sequence of milestones interpolating between zero-mode detection and quantum computing that includes (1) detection of fusion rules for non-Abelian anyons using either proximal charge sensors or pumped current, (2) validation of a prototype topological qubit, and (3) demonstration of non-Abelian statistics by braiding in a branched geometry. The first two milestones require only a single wire with two islands, and additionally enable sensitive measurements of the system\'s excitation gap, quasiparticle poisoning rates, residual Majorana zero-mode splittings, and topological-qubit coherence times. These pre-braiding experiments can be adapted to other manipulation and read out schemes as well.
AU - Aasen, David
AU - Hell, Michael
AU - Mishmash, Ryan
AU - Higginbotham, Andrew P
AU - Danon, Jeroen
AU - Leijnse, Martin
AU - Jespersen, Thomas
AU - Folk, Joshua
AU - Marcs, Charles
AU - Flensberg, Karsten
AU - Alicea, Jason
ID - 100
IS - 3
JF - Physical Review X
TI - Milestones toward Majorana-based quantum computing
VL - 6
ER -
TY - JOUR
AB - Feedback loops in biological networks, among others, enable differentiation and cell cycle progression, and increase robustness in signal transduction. In natural networks, feedback loops are often complex and intertwined, making it challenging to identify which loops are mainly responsible for an observed behavior. However, minimal synthetic replicas could allow for such identification. Here, we engineered a synthetic permease-inducer-repressor system in Saccharomyces cerevisiae to analyze if a transport-mediated positive feedback loop could be a core mechanism for the switch-like behavior in the regulation of metabolic gene networks such as the S. cerevisiae GAL system or the Escherichia coli lac operon. We characterized the synthetic circuit using deterministic and stochastic mathematical models. Similar to its natural counterparts, our synthetic system shows bistable and hysteretic behavior, and the inducer concentration range for bistability as well as the switching rates between the two stable states depend on the repressor concentration. Our results indicate that a generic permease–inducer–repressor circuit with a single feedback loop is sufficient to explain the experimentally observed bistable behavior of the natural systems. We anticipate that the approach of reimplementing natural systems with orthogonal parts to identify crucial network components is applicable to other natural systems such as signaling pathways.
AU - Gnügge, Robert
AU - Dharmarajan, Lekshmi
AU - Lang, Moritz
AU - Stelling, Jörg
ID - 1008
IS - 10
JF - ACS Synthetic Biology
TI - An orthogonal permease–inducer–repressor feedback loop shows bistability
VL - 5
ER -
TY - JOUR
AB - Majorana zero modes are quasiparticle excitations in condensed matter systems that have been proposed as building blocks of fault-tolerant quantum computers. They are expected to exhibit non-Abelian particle statistics, in contrast to the usual statistics of fermions and bosons, enabling quantum operations to be performed by braiding isolated modes around one another. Quantum braiding operations are topologically protected insofar as these modes are pinned near zero energy, with the departure from zero expected to be exponentially small as the modes become spatially separated. Following theoretical proposals, several experiments have identified signatures of Majorana modes in nanowires with proximity-induced superconductivity and atomic chains, with small amounts of mode splitting potentially explained by hybridization of Majorana modes. Here, we use Coulomb-blockade spectroscopy in an InAs nanowire segment with epitaxial aluminium, which forms a proximity-induced superconducting Coulomb island (a â ∼ Majorana islandâ (tm)) that is isolated from normal-metal leads by tunnel barriers, to measure the splitting of near-zero-energy Majorana modes. We observe exponential suppression of energy splitting with increasing wire length. For short devices of a few hundred nanometres, sub-gap state energies oscillate as the magnetic field is varied, as is expected for hybridized Majorana modes. Splitting decreases by a factor of about ten for each half a micrometre of increased wire length. For devices longer than about one micrometre, transport in strong magnetic fields occurs through a zero-energy state that is energetically isolated from a continuum, yielding uniformly spaced Coulomb-blockade conductance peaks, consistent with teleportation via Majorana modes. Our results help to explain the trivial-to-topological transition in finite systems and to quantify the scaling of topological protection with end-mode separation.
AU - Albrecht, S M
AU - Higginbotham, Andrew P
AU - Jespersen, Thomas
AU - Madsen, Morten
AU - Kuemmeth, Ferdinand
AU - Nygård, Jesper
AU - Krogstrup, Peter
AU - Marcus, Charles
ID - 101
IS - 7593
JF - Nature
TI - Exponential protection of zero modes in Majorana islands
VL - 531
ER -
TY - JOUR
AB - Recent experiments have produced mounting evidence of Majorana zero modes in nanowire-superconductor hybrids. Signatures of an expected topological phase transition accompanying the onset of these modes nevertheless remain elusive. We investigate a fundamental question concerning this issue: Do well-formed Majorana modes necessarily entail a sharp phase transition in these setups? Assuming reasonable parameters, we argue that finite-size effects can dramatically smooth this putative transition into a crossover, even in systems large enough to support well-localized Majorana modes. We propose overcoming such finite-size effects by examining the behavior of low-lying excited states through tunneling spectroscopy. In particular, the excited-state energies exhibit characteristic field and density dependence, and scaling with system size, that expose an approaching topological phase transition. We suggest several experiments for extracting the predicted behavior. As a useful byproduct, the protocols also allow one to measure the wire's spin-orbit coupling directly in its superconducting environment.
AU - Mishmash, Ryan
AU - Aasen, David
AU - Higginbotham, Andrew P
AU - Alicea, Jason
ID - 102
IS - 24
JF - Physical Review B
TI - Approaching a topological phase transition in Majorana nanowires
VL - 93
ER -
TY - JOUR
AB - Far-field super-resolution fluorescence microscopy discerns fluorophores residing closer than the diffraction barrier by briefly transferring them in different (typically ON and OFF) states before detection. In coordinate-targeted super-resolution variants, such as stimulated emission depletion (STED) microscopy, this state difference is created by the intensity minima and maxima of an optical pattern, causing all fluorophores to assume the off state, for instance, except at the minima. Although strong spatial confinement of the on state enables high resolution, it also subjects the fluorophores to excess intensities and state cycles at the maxima. Here, we address these issues by driving the fluorophores into a second off state that is inert to the excess light. By using reversibly switchable fluorescent proteins as labels, our approach reduces bleaching and enhances resolution and contrast in live-cell STED microscopy. Using two or more transitions to off states is a useful strategy for augmenting the power of coordinate-targeted super-resolution microscopy.
AU - Danzl, Johann G
AU - Sidenstein, Sven
AU - Gregor, Carola
AU - Urban, Nicolai
AU - Ilgen, Peter
AU - Jakobs, Stefan
AU - Hell, Stefan
ID - 1057
IS - 2
JF - Nature Photonics
TI - Coordinate-targeted fluorescence nanoscopy with multiple off states
VL - 10
ER -
TY - JOUR
AB - A range of bright and photostable rhodamines and carbopyronines with absorption maxima in the range of λ=500-630 nm were prepared, and enabled the specific labeling of cytoskeletal filaments using HaloTag technology followed by staining with 1 μm solutions of the dye-ligand conjugates. The synthesis, photophysical parameters, fluorogenic behavior, and structure-property relationships of the new dyes are discussed. Light microscopy with stimulated emission depletion (STED) provided one- and two-color images of living cells with an optical resolution of 40-60 nm.
AU - Butkevich, Alexey
AU - Mitronova, Gyuzel
AU - Sidenstein, Sven
AU - Klocke, Jessica
AU - Kamin, Dirk
AU - Meineke, Dirk
AU - D'Este, Elisa
AU - Kraemer, Philip
AU - Danzl, Johann G
AU - Belov, Vladimir
AU - Hell, Stefan
ID - 1059
IS - 10
JF - Angewandte Chemie - International Edition
TI - Fluorescent rhodamines and fluorogenic carbopyronines for super-resolution STED microscopy in living cells
VL - 55
ER -
TY - JOUR
AB - Superresolution fluorescence microscopy of multiple fluorophores still requires development. Here we present simultaneous three-colour stimulated emission depletion (STED) nanoscopy relying on a single STED beam at 620 nm. Toggling the STED beam between two or more power levels ("multilevelSTEDv) optimizes resolution and contrast in all colour channels, which are intrinsically co-aligned and well separated. Three-colour recording is demonstrated by imaging the nanoscale cytoskeletal organization in cultured hippocampal neurons. The down to ∼35 nm resolution identified periodic actin/betaII spectrin lattices along dendrites and spines; however, at presynaptic and postsynaptic sites, these patterns were found to be absent. Both our multicolour scheme and the 620 nm STED line should be attractive for routine STED microscopy applications.
AU - Sidenstein, Sven
AU - D'Este, Elisa
AU - Böhm, Marvin
AU - Danzl, Johann G
AU - Belov, Vladimir
AU - Hell, Stefan
ID - 1060
JF - Scientific Reports
TI - Multicolour multilevel STED nanoscopy of actin/spectrin organization at synapses
VL - 6
ER -
TY - CONF
AB - Games on graphs provide the appropriate framework to study several central problems in computer science, such as verification and synthesis of reactive systems. One of the most basic objectives for games on graphs is the liveness (or Büchi) objective that given a target set of vertices requires that some vertex in the target set is visited infinitely often. We study generalized Büchi objectives (i.e., conjunction of liveness objectives), and implications between two generalized Büchi objectives (known as GR(1) objectives), that arise in numerous applications in computer-aided verification. We present improved algorithms and conditional super-linear lower bounds based on widely believed assumptions about the complexity of (A1) combinatorial Boolean matrix multiplication and (A2) CNF-SAT. We consider graph games with n vertices, m edges, and generalized Büchi objectives with k conjunctions. First, we present an algorithm with running time O(k*n^2), improving the previously known O(k*n*m) and O(k^2*n^2) worst-case bounds. Our algorithm is optimal for dense graphs under (A1). Second, we show that the basic algorithm for the problem is optimal for sparse graphs when the target sets have constant size under (A2). Finally, we consider GR(1) objectives, with k_1 conjunctions in the antecedent and k_2 conjunctions in the consequent, and present an O(k_1 k_2 n^{2.5})-time algorithm, improving the previously known O(k_1*k_2*n*m)-time algorithm for m > n^{1.5}.
AU - Chatterjee, Krishnendu
AU - Dvorák, Wolfgang
AU - Henzinger, Monika
AU - Loitzenbauer, Veronika
ID - 1068
TI - Conditionally optimal algorithms for generalized Büchi Games
VL - 58
ER -
TY - CONF
AB - The Continuous Skolem Problem asks whether a real-valued function satisfying a linear differen-
tial equation has a zero in a given interval of real numbers. This is a fundamental reachability
problem for continuous linear dynamical systems, such as linear hybrid automata and continuous-
time Markov chains. Decidability of the problem is currently open – indeed decidability is open
even for the sub-problem in which a zero is sought in a bounded interval. In this paper we show
decidability of the bounded problem subject to Schanuel’s Conjecture, a unifying conjecture in
transcendental number theory. We furthermore analyse the unbounded problem in terms of the
frequencies of the differential equation, that is, the imaginary parts of the characteristic roots.
We show that the unbounded problem can be reduced to the bounded problem if there is at most
one rationally linearly independent frequency, or if there are two rationally linearly independent
frequencies and all characteristic roots are simple. We complete the picture by showing that de-
cidability of the unbounded problem in the case of two (or more) rationally linearly independent
frequencies would entail a major new effectiveness result in Diophantine approximation, namely
computability of the Diophantine-approximation types of all real algebraic numbers.
AU - Chonev, Ventsislav K
AU - Ouaknine, Joël
AU - Worrell, James
ID - 1069
TI - On the skolem problem for continuous linear dynamical systems
VL - 55
ER -
TY - CONF
AB - We present a logic that extends CTL (Computation Tree Logic) with operators that express synchronization properties. A property is synchronized in a system if it holds in all paths of a certain length. The new logic is obtained by using the same path quantifiers and temporal operators as in CTL, but allowing a different order of the quantifiers. This small syntactic variation induces a logic that can express non-regular properties for which known extensions of MSO with equality of path length are undecidable. We show that our variant of CTL is decidable and that the model-checking problem is in Delta_3^P = P^{NP^NP}, and is DP-hard. We analogously consider quantifier exchange in extensions of CTL, and we present operators defined using basic operators of CTL* that express the occurrence of infinitely many synchronization points. We show that the model-checking problem remains in Delta_3^P. The distinguishing power of CTL and of our new logic coincide if the Next operator is allowed in the logics, thus the classical bisimulation quotient can be used for state-space reduction before model checking.
AU - Chatterjee, Krishnendu
AU - Doyen, Laurent
ID - 1070
TI - Computation tree logic for synchronization properties
VL - 55
ER -
TY - CONF
AB - We consider data-structures for answering reachability and distance queries on constant-treewidth graphs with n nodes, on the standard RAM computational model with wordsize W=Theta(log n). Our first contribution is a data-structure that after O(n) preprocessing time, allows (1) pair reachability queries in O(1) time; and (2) single-source reachability queries in O(n/log n) time. This is (asymptotically) optimal and is faster than DFS/BFS when answering more than a constant number of single-source queries. The data-structure uses at all times O(n) space. Our second contribution is a space-time tradeoff data-structure for distance queries. For any epsilon in [1/2,1], we provide a data-structure with polynomial preprocessing time that allows pair queries in O(n^{1-\epsilon} alpha(n)) time, where alpha is the inverse of the Ackermann function, and at all times uses O(n^epsilon) space. The input graph G is not considered in the space complexity.
AU - Chatterjee, Krishnendu
AU - Ibsen-Jensen, Rasmus
AU - Pavlogiannis, Andreas
ID - 1071
TI - Optimal reachability and a space time tradeoff for distance queries in constant treewidth graphs
VL - 57
ER -
TY - JOUR
AB - The asymmetric localization of proteins in the plasma membrane domains of eukaryotic cells is a fundamental manifestation of cell polarity that is central to multicellular organization and developmental patterning. In plants, the mechanisms underlying the polar localization of cargo proteins are still largely unknown and appear to be fundamentally distinct from those operating in mammals. Here, we present a systematic, quantitative comparative analysis of the polar delivery and subcellular localization of proteins that characterize distinct polar plasma membrane domains in plant cells. The combination of microscopic analyses and computational modeling revealed a mechanistic framework common to diverse polar cargos and underlying the establishment and maintenance of apical, basal, and lateral polar domains in plant cells. This mechanism depends on the polar secretion, constitutive endocytic recycling, and restricted lateral diffusion of cargos within the plasma membrane. Moreover, our observations suggest that polar cargo distribution involves the individual protein potential to form clusters within the plasma membrane and interact with the extracellular matrix. Our observations provide insights into the shared cellular mechanisms of polar cargo delivery and polarity maintenance in plant cells.
AU - Łangowski, Łukasz
AU - Wabnik, Krzysztof T
AU - Li, Hongjiang
AU - Vanneste, Steffen
AU - Naramoto, Satoshi
AU - Tanaka, Hirokazu
AU - Friml, Jirí
ID - 1081
JF - Cell Discovery
TI - Cellular mechanisms for cargo delivery and polarity maintenance at different polar domains in plant cells
VL - 2
ER -
TY - CONF
AB - In many applications, it is desirable to extract only the relevant aspects of data. A principled way to do this is the information bottleneck (IB) method, where one seeks a code that maximises information about a relevance variable, Y, while constraining the information encoded about the original data, X. Unfortunately however, the IB method is computationally demanding when data are high-dimensional and/or non-gaussian. Here we propose an approximate variational scheme for maximising a lower bound on the IB objective, analogous to variational EM. Using this method, we derive an IB algorithm to recover features that are both relevant and sparse. Finally, we demonstrate how kernelised versions of the algorithm can be used to address a broad range of problems with non-linear relation between X and Y.
AU - Chalk, Matthew J
AU - Marre, Olivier
AU - Tkacik, Gasper
ID - 1082
TI - Relevant sparse codes with variational information bottleneck
VL - 29
ER -
TY - JOUR
AB - Cholecystokinin-expressing interneurons (CCK-INs) mediate behavior state-dependent inhibition in cortical circuits and themselves receive strong GABAergic input. However, it remains unclear to what extent GABABreceptors (GABABRs) contribute to their inhibitory control. Using immunoelectron microscopy, we found that CCK-INs in the rat hippocampus possessed high levels of dendritic GABABRs and KCTD12 auxiliary proteins, whereas postsynaptic effector Kir3 channels were present at lower levels. Consistently, whole-cell recordings revealed slow GABABR-mediated inhibitory postsynaptic currents (IPSCs) in most CCK-INs. In spite of the higher surface density of GABABRs in CCK-INs than in CA1 principal cells, the amplitudes of IPSCs were comparable, suggesting that the expression of Kir3 channels is the limiting factor for the GABABR currents in these INs. Morphological analysis showed that CCK-INs were diverse, comprising perisomatic-targeting basket cells (BCs), as well as dendrite-targeting (DT) interneurons, including a previously undescribed DT type. GABABR-mediated IPSCs in CCK-INs were large in BCs, but small in DT subtypes. In response to prolonged activation, GABABR-mediated currents displayed strong desensitization, which was absent in KCTD12-deficient mice. This study highlights that GABABRs differentially control CCK-IN subtypes, and the kinetics and desensitization of GABABR-mediated currents are modulated by KCTD12 proteins.
AU - Booker, Sam
AU - Althof, Daniel
AU - Gross, Anna
AU - Loreth, Desiree
AU - Müller, Johanna
AU - Unger, Andreas
AU - Fakler, Bernd
AU - Varro, Andrea
AU - Watanabe, Masahiko
AU - Gassmann, Martin
AU - Bettler, Bernhard
AU - Shigemoto, Ryuichi
AU - Vida, Imre
AU - Kulik, Ákos
ID - 1083
IS - 3
JF - Cerebral Cortex
TI - KCTD12 auxiliary proteins modulate kinetics of GABAB receptor-mediated inhibition in Cholecystokinin-containing interneurons
VL - 27
ER -
TY - JOUR
AB - Cell geometry is tightly coupled to gene expression patterns within the tissue microenvironment. This perspective synthesizes evidence that the 3D organization of chromosomes is a critical intermediate for geometric control of genomic programs. Using a combination of experiments and modeling we outline approaches to decipher the mechano-genomic code that governs cellular homeostasis and reprogramming.
AU - Uhler, Caroline
AU - Shivashankar, G V
ID - 1088
IS - 4
JF - BioArchitecture
TI - Geometric control and modeling of genome reprogramming
VL - 6
ER -
TY - CONF
AB - While weighted automata provide a natural framework to express quantitative properties, many basic properties like average response time cannot be expressed with weighted automata. Nested weighted automata extend weighted automata and consist of a master automaton and a set of slave automata that are invoked by the master automaton. Nested weighted automata are strictly more expressive than weighted automata (e.g., average response time can be expressed with nested weighted automata), but the basic decision questions have higher complexity (e.g., for deterministic automata, the emptiness question for nested weighted automata is PSPACE-hard, whereas the corresponding complexity for weighted automata is PTIME). We consider a natural subclass of nested weighted automata where at any point at most a bounded number k of slave automata can be active. We focus on automata whose master value function is the limit average. We show that these nested weighted automata with bounded width are strictly more expressive than weighted automata (e.g., average response time with no overlapping requests can be expressed with bound k=1, but not with non-nested weighted automata). We show that the complexity of the basic decision problems (i.e., emptiness and universality) for the subclass with k constant matches the complexity for weighted automata. Moreover, when k is part of the input given in unary we establish PSPACE-completeness.
AU - Chatterjee, Krishnendu
AU - Henzinger, Thomas A
AU - Otop, Jan
ID - 1090
TI - Nested weighted limit-average automata of bounded width
VL - 58
ER -
TY - CONF
AB - We introduce a general class of distances (metrics) between Markov chains, which are based on linear behaviour. This class encompasses distances given topologically (such as the total variation distance or trace distance) as well as by temporal logics or automata. We investigate which of the distances can be approximated by observing the systems, i.e. by black-box testing or simulation, and we provide both negative and positive results.
AU - Daca, Przemyslaw
AU - Henzinger, Thomas A
AU - Kretinsky, Jan
AU - Petrov, Tatjana
ID - 1093
TI - Linear distances between Markov chains
VL - 59
ER -
TY - CHAP
AB - Immunogold labeling of freeze-fracture replicas has recently been used for high-resolution visualization of protein localization in electron microscopy. This method has higher labeling efficiency than conventional immunogold methods for membrane molecules allowing precise quantitative measurements. However, one of the limitations of freeze-fracture replica immunolabeling is difficulty in keeping structural orientation and identifying labeled profiles in complex tissues like brain. The difficulty is partly due to fragmentation of freeze-fracture replica preparations during labeling procedures and limited morphological clues on the replica surface. To overcome these issues, we introduce here a grid-glued replica method combined with SEM observation. This method allows histological staining before dissolving the tissue and easy handling of replicas during immunogold labeling, and keeps the whole replica surface intact without fragmentation. The procedure described here is also useful for matched double-replica analysis allowing further identification of labeled profiles in corresponding P-face and E-face.
AU - Harada, Harumi
AU - Shigemoto, Ryuichi
ID - 1094
T2 - High-Resolution Imaging of Cellular Proteins
TI - Immunogold protein localization on grid-glued freeze-fracture replicas
VL - 1474
ER -
TY - CONF
AB - The semantics of concurrent data structures is usually given by a sequential specification and a consistency condition. Linearizability is the most popular consistency condition due to its simplicity and general applicability. Nevertheless, for applications that do not require all guarantees offered by linearizability, recent research has focused on improving performance and scalability of concurrent data structures by relaxing their semantics. In this paper, we present local linearizability, a relaxed consistency condition that is applicable to container-type concurrent data structures like pools, queues, and stacks. While linearizability requires that the effect of each operation is observed by all threads at the same time, local linearizability only requires that for each thread T, the effects of its local insertion operations and the effects of those removal operations that remove values inserted by T are observed by all threads at the same time. We investigate theoretical and practical properties of local linearizability and its relationship to many existing consistency conditions. We present a generic implementation method for locally linearizable data structures that uses existing linearizable data structures as building blocks. Our implementations show performance and scalability improvements over the original building blocks and outperform the fastest existing container-type implementations.
AU - Haas, Andreas
AU - Henzinger, Thomas A
AU - Holzer, Andreas
AU - Kirsch, Christoph
AU - Lippautz, Michael
AU - Payer, Hannes
AU - Sezgin, Ali
AU - Sokolova, Ana
AU - Veith, Helmut
ID - 1095
T2 - Leibniz International Proceedings in Informatics
TI - Local linearizability for concurrent container-type data structures
VL - 59
ER -