TY - JOUR
AB - The accuracy of interdisciplinarity measurements is directly related to the quality of the underlying bibliographic data. Existing indicators of interdisciplinarity are not capable of reflecting the inaccuracies introduced by incorrect and incomplete records because correct and complete bibliographic data can rarely be obtained. This is the case for the Rao–Stirling index, which cannot handle references that are not categorized into disciplinary fields. We introduce a method that addresses this problem. It extends the Rao–Stirling index to acknowledge missing data by calculating its interval of uncertainty using computational optimization. The evaluation of our method indicates that the uncertainty interval is not only useful for estimating the inaccuracy of interdisciplinarity measurements, but it also delivers slightly more accurate aggregated interdisciplinarity measurements than the Rao–Stirling index.
AU - Calatrava Moreno, Maria
AU - Auzinger, Thomas
AU - Werthner, Hannes
ID - 1446
IS - 1
JF - Scientometrics
TI - On the uncertainty of interdisciplinarity measurements due to incomplete bibliographic data
VL - 107
ER -
TY - JOUR
AB - We develop a new and systematic method for proving entropic Ricci curvature lower bounds for Markov chains on discrete sets. Using different methods, such bounds have recently been obtained in several examples (e.g., 1-dimensional birth and death chains, product chains, Bernoulli–Laplace models, and random transposition models). However, a general method to obtain discrete Ricci bounds had been lacking. Our method covers all of the examples above. In addition we obtain new Ricci curvature bounds for zero-range processes on the complete graph. The method is inspired by recent work of Caputo, Dai Pra and Posta on discrete functional inequalities.
AU - Fathi, Max
AU - Maas, Jan
ID - 1448
IS - 3
JF - The Annals of Applied Probability
TI - Entropic Ricci curvature bounds for discrete interacting systems
VL - 26
ER -
TY - JOUR
AB - The actin cytoskeleton plays important roles in the formation and internalization of endocytic vesicles. In yeast, endocytic vesicles move towards early endosomes along actin cables, however, the molecular machinery regulating interaction between endocytic vesicles and actin cables is poorly understood. The Eps15-like protein Pan1p plays a key role in actin-mediated endocytosis and is negatively regulated by Ark1 and Prk1 kinases. Here we show that pan1 mutated to prevent phosphorylation at all 18 threonines, pan1-18TA, displayed almost the same endocytic defect as ark1Δ prk1Δ cells, and contained abnormal actin concentrations including several endocytic compartments. Early endosomes were highly localized in the actin concentrations and displayed movement along actin cables. The dephosphorylated form of Pan1p also caused stable associations between endocytic vesicles and actin cables, and between endocytic vesicles and endosomes. Thus Pan1 phosphorylation is part of a novel mechanism that regulates endocytic compartment interactions with each other and with actin cables.
AU - Toshima, Junko
AU - Furuya, Eri
AU - Nagano, Makoto
AU - Kanno, Chisa
AU - Sakamoto, Yuta
AU - Ebihara, Masashi
AU - Siekhaus, Daria E
AU - Toshima, Jiro
ID - 1475
IS - February 2016
JF - eLife
TI - Yeast Eps15-like endocytic protein Pan1p regulates the interaction between endocytic vesicles, endosomes and the actin cytoskeleton
VL - 5
ER -
TY - JOUR
AB - The dynamic assembly and disassembly of actin filaments is essential for the formation and transport of vesicles during endocytosis. In yeast, two types of actin structures, namely cortical patches and cytoplasmic cables, play a direct role in endocytosis, but how their interaction is regulated remains unclear. Here, we show that Srv2/CAP, an evolutionarily conserved actin regulator, is required for efficient endocytosis owing to its role in the formation of the actin patches that aid initial vesicle invagination and of the actin cables that these move along. Deletion of the SRV2 gene resulted in the appearance of aberrant fragmented actin cables that frequently moved past actin patches, the sites of endocytosis. We find that the C-terminal CARP domain of Srv2p is vitally important for the proper assembly of actin patches and cables; we also demonstrate that the N-terminal helical folded domain of Srv2 is required for its localization to actin patches, specifically to the ADP-actin rich region through an interaction with cofilin. These results demonstrate the in vivo roles of Srv2p in the regulation of the actin cytoskeleton during clathrin-mediated endocytosis
AU - Toshima, Junko
AU - Horikomi, Chika
AU - Okada, Asuka
AU - Hatori, Makiko
AU - Nagano, Makoto
AU - Masuda, Atsushi
AU - Yamamoto, Wataru
AU - Siekhaus, Daria E
AU - Toshima, Jiro
ID - 1476
IS - 2
JF - Journal of Cell Science
TI - Srv2/CAP is required for polarized actin cable assembly and patch internalization during clathrin-mediated endocytosis
VL - 129
ER -
TY - JOUR
AB - We consider partially observable Markov decision processes (POMDPs) with ω-regular conditions specified as parity objectives. The class of ω-regular languages provides a robust specification language to express properties in verification, and parity objectives are canonical forms to express them. The qualitative analysis problem given a POMDP and a parity objective asks whether there is a strategy to ensure that the objective is satisfied with probability 1 (resp. positive probability). While the qualitative analysis problems are undecidable even for special cases of parity objectives, we establish decidability (with optimal complexity) for POMDPs with all parity objectives under finite-memory strategies. We establish optimal (exponential) memory bounds and EXPTIME-completeness of the qualitative analysis problems under finite-memory strategies for POMDPs with parity objectives. We also present a practical approach, where we design heuristics to deal with the exponential complexity, and have applied our implementation on a number of POMDP examples.
AU - Chatterjee, Krishnendu
AU - Chmelik, Martin
AU - Tracol, Mathieu
ID - 1477
IS - 5
JF - Journal of Computer and System Sciences
TI - What is decidable about partially observable Markov decision processes with ω-regular objectives
VL - 82
ER -
TY - JOUR
AB - We consider the Tonks-Girardeau gas subject to a random external potential. If the disorder is such that the underlying one-particle Hamiltonian displays localization (which is known to be generically the case), we show that there is exponential decay of correlations in the many-body eigenstates. Moreover, there is no Bose-Einstein condensation and no superfluidity, even at zero temperature.
AU - Seiringer, Robert
AU - Warzel, Simone
ID - 1478
IS - 3
JF - New Journal of Physics
TI - Decay of correlations and absence of superfluidity in the disordered Tonks-Girardeau gas
VL - 18
ER -
TY - JOUR
AB - Most entropy notions H(.) like Shannon or min-entropy satisfy a chain rule stating that for random variables X,Z, and A we have H(X|Z,A)≥H(X|Z)−|A|. That is, by conditioning on A the entropy of X can decrease by at most the bitlength |A| of A. Such chain rules are known to hold for some computational entropy notions like Yao’s and unpredictability-entropy. For HILL entropy, the computational analogue of min-entropy, the chain rule is of special interest and has found many applications, including leakage-resilient cryptography, deterministic encryption, and memory delegation. These applications rely on restricted special cases of the chain rule. Whether the chain rule for conditional HILL entropy holds in general was an open problem for which we give a strong negative answer: we construct joint distributions (X,Z,A), where A is a distribution over a single bit, such that the HILL entropy H HILL (X|Z) is large but H HILL (X|Z,A) is basically zero.
Our counterexample just makes the minimal assumption that NP⊈P/poly. Under the stronger assumption that injective one-way function exist, we can make all the distributions efficiently samplable.
Finally, we show that some more sophisticated cryptographic objects like lossy functions can be used to sample a distribution constituting a counterexample to the chain rule making only a single invocation to the underlying object.
AU - Krenn, Stephan
AU - Pietrzak, Krzysztof Z
AU - Wadia, Akshay
AU - Wichs, Daniel
ID - 1479
IS - 3
JF - Computational Complexity
TI - A counterexample to the chain rule for conditional HILL entropy
VL - 25
ER -
TY - JOUR
AB - Exponential varieties arise from exponential families in statistics. These real algebraic varieties have strong positivity and convexity properties, familiar from toric varieties and their moment maps. Among them are varieties of inverses of symmetric matrices satisfying linear constraints. This class includes Gaussian graphical models. We develop a general theory of exponential varieties. These are derived from hyperbolic polynomials and their integral representations. We compare the multidegrees and ML degrees of the gradient map for hyperbolic polynomials.
AU - Michałek, Mateusz
AU - Sturmfels, Bernd
AU - Uhler, Caroline
AU - Zwiernik, Piotr
ID - 1480
IS - 1
JF - Proceedings of the London Mathematical Society
TI - Exponential varieties
VL - 112
ER -
TY - JOUR
AB - Plants have the ability to continously generate new organs by maintaining populations of stem cells throught their lives. The shoot apical meristem (SAM) provides a stable environment for the maintenance of stem cells. All cells inside the SAM divide, yet boundaries and patterns are maintained. Experimental evidence indicates that patterning is independent of cell lineage, thus a dynamic self-regulatory mechanism is required. A pivotal role in the organization of the SAM is played by the WUSCHEL gene (WUS). An important question in this regard is that how WUS expression is positioned in the SAM via a cell-lineage independent signaling mechanism. In this study we demonstrate via mathematical modeling that a combination of an inhibitor of the Cytokinin (CK) receptor, Arabidopsis histidine kinase 4 (AHK4) and two morphogens originating from the top cell layer, can plausibly account for the cell lineage-independent centering of WUS expression within SAM. Furthermore, our laser ablation and microsurgical experiments support the hypothesis that patterning in SAM occurs at the level of CK reception and signaling. The model suggests that the interplay between CK signaling, WUS/CLV feedback loop and boundary signals can account for positioning of the WUS expression, and provides directions for further experimental investigation.
AU - Adibi, Milad
AU - Yoshida, Saiko
AU - Weijers, Dolf
AU - Fleck, Christian
ID - 1482
IS - 2
JF - PLoS One
TI - Centering the organizing center in the Arabidopsis thaliana shoot apical meristem by a combination of cytokinin signaling and self-organization
VL - 11
ER -
TY - JOUR
AU - Chen, Xu
AU - Wu, Shuang
AU - Liu, Zengyu
AU - Friml, Jiřĺ
ID - 1484
IS - 6
JF - Trends in Cell Biology
TI - Environmental and endogenous control of cortical microtubule orientation
VL - 26
ER -
TY - JOUR
AB - In this article the notion of metabolic turnover is revisited in the light of recent results of out-of-equilibrium thermodynamics. By means of Monte Carlo methods we perform an exact sampling of the enzymatic fluxes in a genome scale metabolic network of E. Coli in stationary growth conditions from which we infer the metabolites turnover times. However the latter are inferred from net fluxes, and we argue that this approximation is not valid for enzymes working nearby thermodynamic equilibrium. We recalculate turnover times from total fluxes by performing an energy balance analysis of the network and recurring to the fluctuation theorem. We find in many cases values one of order of magnitude lower, implying a faster picture of intermediate metabolism.
AU - De Martino, Daniele
ID - 1485
IS - 1
JF - Physical Biology
TI - Genome-scale estimate of the metabolic turnover of E. Coli from the energy balance analysis
VL - 13
ER -
TY - JOUR
AB - We review recent results concerning the mathematical properties of the Bardeen-Cooper-Schrieffer (BCS) functional of superconductivity, which were obtained in a series of papers, partly in collaboration with R. Frank, E. Hamza, S. Naboko, and J. P. Solovej. Our discussion includes, in particular, an investigation of the critical temperature for a general class of interaction potentials, as well as a study of its dependence on external fields. We shall explain how the Ginzburg-Landau model can be derived from the BCS theory in a suitable parameter regime.
AU - Hainzl, Christian
AU - Seiringer, Robert
ID - 1486
IS - 2
JF - Journal of Mathematical Physics
TI - The Bardeen–Cooper–Schrieffer functional of superconductivity and its mathematical properties
VL - 57
ER -
TY - JOUR
AB - Rhythms with time scales of multiple cycles per second permeate the mammalian brain, yet neuroscientists are not certain of their functional roles. One leading idea is that coherent oscillation between two brain regions facilitates the exchange of information between them. In rats, the hippocampus and the vibrissal sensorimotor system both are characterized by rhythmic oscillation in the theta range, 5–12 Hz. Previous work has been divided as to whether the two rhythms are independent or coherent. To resolve this question, we acquired three measures from rats—whisker motion, hippocampal local field potential (LFP), and barrel cortex unit firing—during a whisker-mediated texture discrimination task and during control conditions (not engaged in a whisker-mediated memory task). Compared to control conditions, the theta band of hippocampal LFP showed a marked increase in power as the rats approached and then palpated the texture. Phase synchronization between whisking and hippocampal LFP increased by almost 50% during approach and texture palpation. In addition, a greater proportion of barrel cortex neurons showed firing that was phase-locked to hippocampal theta while rats were engaged in the discrimination task. Consistent with a behavioral consequence of phase synchronization, the rats identified the texture more rapidly and with lower error likelihood on trials in which there was an increase in theta-whisking coherence at the moment of texture palpation. These results suggest that coherence between the whisking rhythm, barrel cortex firing, and hippocampal LFP is augmented selectively during epochs in which the rat collects sensory information and that such coherence enhances the efficiency of integration of stimulus information into memory and decision-making centers.
AU - Grion, Natalia
AU - Akrami, Athena
AU - Zuo, Yangfang
AU - Stella, Federico
AU - Diamond, Mathew
ID - 1487
IS - 2
JF - PLoS Biology
TI - Coherence between rat sensorimotor system and hippocampus is enhanced during tactile discrimination
VL - 14
ER -
TY - JOUR
AB - We prove optimal local law, bulk universality and non-trivial decay for the off-diagonal elements of the resolvent for a class of translation invariant Gaussian random matrix ensembles with correlated entries.
AU - Ajanki, Oskari H
AU - Erdös, László
AU - Krüger, Torben H
ID - 1489
IS - 2
JF - Journal of Statistical Physics
TI - Local spectral statistics of Gaussian matrices with correlated entries
VL - 163
ER -
TY - JOUR
AB - To induce adaptive immunity, dendritic cells (DCs) migrate through afferent lymphatic vessels (LVs) to draining lymph nodes (dLNs). This process occurs in several consecutive steps. Upon entry into lymphatic capillaries, DCs first actively crawl into downstream collecting vessels. From there, they are next passively and rapidly transported to the dLN by lymph flow. Here, we describe a role for the chemokine CCL21 in intralymphatic DC crawling. Performing time-lapse imaging in murine skin, we found that blockade of CCL21-but not the absence of lymph flow-completely abolished DC migration from capillaries toward collecting vessels and reduced the ability of intralymphatic DCs to emigrate from skin. Moreover, we found that in vitro low laminar flow established a CCL21 gradient along lymphatic endothelial monolayers, thereby inducing downstream-directed DC migration. These findings reveal a role for intralymphatic CCL21 in promoting DC trafficking to dLNs, through the formation of a flow-induced gradient.
AU - Russo, Erica
AU - Teijeira, Alvaro
AU - Vaahtomeri, Kari
AU - Willrodt, Ann
AU - Bloch, Joël
AU - Nitschké, Maximilian
AU - Santambrogio, Laura
AU - Kerjaschki, Dontscho
AU - Sixt, Michael K
AU - Halin, Cornelia
ID - 1490
IS - 7
JF - Cell Reports
TI - Intralymphatic CCL21 promotes tissue egress of dendritic cells through afferent lymphatic vessels
VL - 14
ER -
TY - JOUR
AB - We study the ground state of a trapped Bose gas, starting from the full many-body Schrödinger Hamiltonian, and derive the non-linear Schrödinger energy functional in the limit of a large particle number, when the interaction potential converges slowly to a Dirac delta function. Our method is based on quantitative estimates on the discrepancy between the full many-body energy and its mean-field approximation using Hartree states. These are proved using finite dimensional localization and a quantitative version of the quantum de Finetti theorem. Our approach covers the case of attractive interactions in the regime of stability. In particular, our main new result is a derivation of the 2D attractive non-linear Schrödinger ground state.
AU - Lewin, Mathieu
AU - Nam, Phan
AU - Rougerie, Nicolas
ID - 1491
IS - 9
JF - Transactions of the American Mathematical Society
TI - The mean-field approximation and the non-linear Schrödinger functional for trapped Bose gases
VL - 368
ER -
TY - JOUR
AB - To sustain a lifelong ability to initiate organs, plants retain pools of undifferentiated cells with a preserved prolif eration capacity. The root pericycle represents a unique tissue with conditional meristematic activity, and its tight control determines initiation of lateral organs. Here we show that the meristematic activity of the pericycle is constrained by the interaction with the adjacent endodermis. Release of these restraints by elimination of endo dermal cells by single-cell ablation triggers the pericycle to re-enter the cell cycle. We found that endodermis removal substitutes for the phytohormone auxin-dependent initiation of the pericycle meristematic activity. However, auxin is indispensable to steer the cell division plane orientation of new organ-defining divisions. We propose a dual, spatiotemporally distinct role for auxin during lateral root initiation. In the endodermis, auxin releases constraints arising from cell-to-cell interactions that compromise the pericycle meristematic activity, whereas, in the pericycle, auxin defines the orientation of the cell division plane to initiate lateral roots.
AU - Marhavy, Peter
AU - Montesinos López, Juan C
AU - Abuzeineh, Anas
AU - Van Damme, Daniël
AU - Vermeer, Joop
AU - Duclercq, Jérôme
AU - Rakusova, Hana
AU - Marhavá, Petra
AU - Friml, Jirí
AU - Geldner, Niko
AU - Benková, Eva
ID - 1492
IS - 4
JF - Genes and Development
TI - Targeted cell elimination reveals an auxin-guided biphasic mode of lateral root initiation
VL - 30
ER -
TY - JOUR
AB - We introduce a new method for deriving the time-dependent Hartree or Hartree-Fock equations as an effective mean-field dynamics from the microscopic Schrödinger equation for fermionic many-particle systems in quantum mechanics. The method is an adaption of the method used in Pickl (Lett. Math. Phys. 97 (2) 151–164 2011) for bosonic systems to fermionic systems. It is based on a Gronwall type estimate for a suitable measure of distance between the microscopic solution and an antisymmetrized product state. We use this method to treat a new mean-field limit for fermions with long-range interactions in a large volume. Some of our results hold for singular attractive or repulsive interactions. We can also treat Coulomb interaction assuming either a mild singularity cutoff or certain regularity conditions on the solutions to the Hartree(-Fock) equations. In the considered limit, the kinetic and interaction energy are of the same order, while the average force is subleading. For some interactions, we prove that the Hartree(-Fock) dynamics is a more accurate approximation than a simpler dynamics that one would expect from the subleading force. With our method we also treat the mean-field limit coupled to a semiclassical limit, which was discussed in the literature before, and we recover some of the previous results. All results hold for initial data close (but not necessarily equal) to antisymmetrized product states and we always provide explicit rates of convergence.
AU - Petrat, Sören P
AU - Pickl, Peter
ID - 1493
IS - 1
JF - Mathematical Physics, Analysis and Geometry
TI - A new method and a new scaling for deriving fermionic mean-field dynamics
VL - 19
ER -
TY - JOUR
AB - Turbulence is one of the most frequently encountered non-equilibrium phenomena in nature, yet characterizing the transition that gives rise to turbulence in basic shear flows has remained an elusive task. Although, in recent studies, critical points marking the onset of sustained turbulence have been determined for several such flows, the physical nature of the transition could not be fully explained. In extensive experimental and computational studies we show for the example of Couette flow that the onset of turbulence is a second-order phase transition and falls into the directed percolation universality class. Consequently, the complex laminar–turbulent patterns distinctive for the onset of turbulence in shear flows result from short-range interactions of turbulent domains and are characterized by universal critical exponents. More generally, our study demonstrates that even high-dimensional systems far from equilibrium such as turbulence exhibit universality at onset and that here the collective dynamics obeys simple rules.
AU - Lemoult, Grégoire M
AU - Shi, Liang
AU - Avila, Kerstin
AU - Jalikop, Shreyas V
AU - Avila, Marc
AU - Hof, Björn
ID - 1494
IS - 3
JF - Nature Physics
TI - Directed percolation phase transition to sustained turbulence in Couette flow
VL - 12
ER -
TY - JOUR
AB - The two-photon 1s2 2s 2p 3P0 1s22s2 1S0 transition in berylliumlike ions is theoretically investigated within a fully relativistic framework and a second-order perturbation theory. We focus our analysis on how electron correlation, as well as the negative-energy spectrum, can affect the forbidden E1M1 decay rate. For this purpose, we include the electronic correlation via an effective local potential and within a single configuration-state model. Due to its experimental interest, evaluations of decay rates are performed for berylliumlike xenon and uranium. We find that the negative-energy contribution can be neglected at the present level of accuracy in the evaluation of the decay rate. On the other hand, if contributions of electronic correlation are not carefully taken into account, it may change the lifetime of the metastable state by up to 20%. By performing a full-relativistic jj-coupling calculation, we found a decrease of the decay rate by two orders of magnitude compared to non-relativistic LS-coupling calculations, for the selected heavy ions.
AU - Amaro, Pedro
AU - Fratini, Filippo
AU - Safari, Laleh
AU - Machado, Jorge
AU - Guerra, Mauro
AU - Indelicato, Paul
AU - Santos, José
ID - 1496
IS - 3
JF - Physical Review A - Atomic, Molecular, and Optical Physics
TI - Relativistic evaluation of the two-photon decay of the metastable 1s22s2p3P0 state in berylliumlike ions with an effective-potential model
VL - 93
ER -
TY - JOUR
AB - The inference of demographic history from genome data is hindered by a lack of efficient computational approaches. In particular, it has proved difficult to exploit the information contained in the distribution of genealogies across the genome. We have previously shown that the generating function (GF) of genealogies can be used to analytically compute likelihoods of demographic models from configurations of mutations in short sequence blocks (Lohse et al. 2011). Although the GF has a simple, recursive form, the size of such likelihood calculations explodes quickly with the number of individuals and applications of this framework have so far been mainly limited to small samples (pairs and triplets) for which the GF can be written by hand. Here we investigate several strategies for exploiting the inherent symmetries of the coalescent. In particular, we show that the GF of genealogies can be decomposed into a set of equivalence classes that allows likelihood calculations from nontrivial samples. Using this strategy, we automated blockwise likelihood calculations for a general set of demographic scenarios in Mathematica. These histories may involve population size changes, continuous migration, discrete divergence, and admixture between multiple populations. To give a concrete example, we calculate the likelihood for a model of isolation with migration (IM), assuming two diploid samples without phase and outgroup information. We demonstrate the new inference scheme with an analysis of two individual butterfly genomes from the sister species Heliconius melpomene rosina and H. cydno.
AU - Lohse, Konrad
AU - Chmelik, Martin
AU - Martin, Simon
AU - Barton, Nicholas H
ID - 1518
IS - 2
JF - Genetics
TI - Efficient strategies for calculating blockwise likelihoods under the coalescent
VL - 202
ER -
TY - JOUR
AB - Complex I (NADH:ubiquinone oxidoreductase) plays a central role in cellular energy production, coupling electron transfer between NADH and quinone to proton translocation. It is the largest protein assembly of respiratory chains and one of the most elaborate redox membrane proteins known. Bacterial enzyme is about half the size of mitochondrial and thus provides its important "minimal" model. Dysfunction of mitochondrial complex I is implicated in many human neurodegenerative diseases. The L-shaped complex consists of a hydrophilic arm, where electron transfer occurs, and a membrane arm, where proton translocation takes place. We have solved the crystal structures of the hydrophilic domain of complex I from Thermus thermophilus, the membrane domain from Escherichia coli and recently of the intact, entire complex I from T. thermophilus (536. kDa, 16 subunits, 9 iron-sulphur clusters, 64 transmembrane helices). The 95. Å long electron transfer pathway through the enzyme proceeds from the primary electron acceptor flavin mononucleotide through seven conserved Fe-S clusters to the unusual elongated quinone-binding site at the interface with the membrane domain. Four putative proton translocation channels are found in the membrane domain, all linked by the central flexible axis containing charged residues. The redox energy of electron transfer is coupled to proton translocation by the as yet undefined mechanism proposed to involve long-range conformational changes. This article is part of a Special Issue entitled Respiratory complex I, edited by Volker Zickermann and Ulrich Brandt.
AU - Berrisford, John
AU - Baradaran, Rozbeh
AU - Sazanov, Leonid A
ID - 1521
IS - 7
JF - Biochimica et Biophysica Acta - Bioenergetics
TI - Structure of bacterial respiratory complex I
VL - 1857
ER -
TY - JOUR
AB - We classify smooth Brunnian (i.e., unknotted on both components) embeddings (S2 × S1) ⊔ S3 → ℝ6. Any Brunnian embedding (S2 × S1) ⊔ S3 → ℝ6 is isotopic to an explicitly constructed embedding fk,m,n for some integers k, m, n such that m ≡ n (mod 2). Two embeddings fk,m,n and fk′ ,m′,n′ are isotopic if and only if k = k′, m ≡ m′ (mod 2k) and n ≡ n′ (mod 2k). We use Haefliger’s classification of embeddings S3 ⊔ S3 → ℝ6 in our proof. The relation between the embeddings (S2 × S1) ⊔ S3 → ℝ6 and S3 ⊔ S3 → ℝ6 is not trivial, however. For example, we show that there exist embeddings f: (S2 ×S1) ⊔ S3 → ℝ6 and g, g′ : S3 ⊔ S3 → ℝ6 such that the componentwise embedded connected sum f # g is isotopic to f # g′ but g is not isotopic to g′.
AU - Avvakumov, Serhii
ID - 1522
IS - 1
JF - Moscow Mathematical Journal
TI - The classification of certain linked 3-manifolds in 6-space
VL - 16
ER -
TY - JOUR
AB - For random graphs, the containment problem considers the probability that a binomial random graph G(n, p) contains a given graph as a substructure. When asking for the graph as a topological minor, i.e., for a copy of a subdivision of the given graph, it is well known that the (sharp) threshold is at p = 1/n. We consider a natural analogue of this question for higher-dimensional random complexes Xk(n, p), first studied by Cohen, Costa, Farber and Kappeler for k = 2. Improving previous results, we show that p = Θ(1/ √n) is the (coarse) threshold for containing a subdivision of any fixed complete 2-complex. For higher dimensions k > 2, we get that p = O(n−1/k) is an upper bound for the threshold probability of containing a subdivision of a fixed k-dimensional complex.
AU - Gundert, Anna
AU - Wagner, Uli
ID - 1523
IS - 4
JF - Proceedings of the American Mathematical Society
TI - On topological minors in random simplicial complexes
VL - 144
ER -
TY - CONF
AB - When designing genetic circuits, the typical primitives used in major existing modelling formalisms are gene interaction graphs, where edges between genes denote either an activation or inhibition relation. However, when designing experiments, it is important to be precise about the low-level mechanistic details as to how each such relation is implemented. The rule-based modelling language Kappa allows to unambiguously specify mechanistic details such as DNA binding sites, dimerisation of transcription factors, or co-operative interactions. Such a detailed description comes with complexity and computationally costly executions. We propose a general method for automatically transforming a rule-based program, by eliminating intermediate species and adjusting the rate constants accordingly. To the best of our knowledge, we show the first automated reduction of rule-based models based on equilibrium approximations.
Our algorithm is an adaptation of an existing algorithm, which was designed for reducing reaction-based programs; our version of the algorithm scans the rule-based Kappa model in search for those interaction patterns known to be amenable to equilibrium approximations (e.g. Michaelis-Menten scheme). Additional checks are then performed in order to verify if the reduction is meaningful in the context of the full model. The reduced model is efficiently obtained by static inspection over the rule-set. The tool is tested on a detailed rule-based model of a λ-phage switch, which lists 92 rules and 13 agents. The reduced model has 11 rules and 5 agents, and provides a dramatic reduction in simulation time of several orders of magnitude.
AU - Beica, Andreea
AU - Guet, Calin C
AU - Petrov, Tatjana
ID - 1524
TI - Efficient reduction of kappa models by static inspection of the rule-set
VL - 9271
ER -
TY - CONF
AB - We present the first study of robustness of systems that are both timed as well as reactive (I/O). We study the behavior of such timed I/O systems in the presence of uncertain inputs and formalize their robustness using the analytic notion of Lipschitz continuity: a timed I/O system is K-(Lipschitz) robust if the perturbation in its output is at most K times the perturbation in its input. We quantify input and output perturbation using similarity functions over timed words such as the timed version of the Manhattan distance and the Skorokhod distance. We consider two models of timed I/O systems — timed transducers and asynchronous sequential circuits. We show that K-robustness of timed transducers can be decided in polynomial space under certain conditions. For asynchronous sequential circuits, we reduce K-robustness w.r.t. timed Manhattan distances to K-robustness of discrete letter-to-letter transducers and show PSpace-completeness of the problem.
AU - Henzinger, Thomas A
AU - Otop, Jan
AU - Samanta, Roopsha
ID - 1526
TI - Lipschitz robustness of timed I/O systems
VL - 9583
ER -
TY - JOUR
AB - We consider partially observable Markov decision processes (POMDPs) with a set of target states and an integer cost associated with every transition. The optimization objective we study asks to minimize the expected total cost of reaching a state in the target set, while ensuring that the target set is reached almost surely (with probability 1). We show that for integer costs approximating the optimal cost is undecidable. For positive costs, our results are as follows: (i) we establish matching lower and upper bounds for the optimal cost, both double exponential in the POMDP state space size; (ii) we show that the problem of approximating the optimal cost is decidable and present approximation algorithms developing on the existing algorithms for POMDPs with finite-horizon objectives. While the worst-case running time of our algorithm is double exponential, we also present efficient stopping criteria for the algorithm and show experimentally that it performs well in many examples of interest.
AU - Chatterjee, Krishnendu
AU - Chmelik, Martin
AU - Gupta, Raghav
AU - Kanodia, Ayush
ID - 1529
JF - Artificial Intelligence
TI - Optimal cost almost-sure reachability in POMDPs
VL - 234
ER -
TY - JOUR
AB - We provide general conditions for which bosonic quadratic Hamiltonians on Fock spaces can be diagonalized by Bogoliubov transformations. Our results cover the case when quantum systems have infinite degrees of freedom and the associated one-body kinetic and paring operators are unbounded. Our sufficient conditions are optimal in the sense that they become necessary when the relevant one-body operators commute.
AU - Nam, Phan
AU - Napiórkowski, Marcin M
AU - Solovej, Jan
ID - 1545
IS - 11
JF - Journal of Functional Analysis
TI - Diagonalization of bosonic quadratic Hamiltonians by Bogoliubov transformations
VL - 270
ER -
TY - JOUR
AB - Antibiotic resistance carries a fitness cost that must be overcome in order for resistance to persist over the long term. Compensatory mutations that recover the functional defects associated with resistance mutations have been argued to play a key role in overcoming the cost of resistance, but compensatory mutations are expected to be rare relative to generally beneficial mutations that increase fitness, irrespective of antibiotic resistance. Given this asymmetry, population genetics theory predicts that populations should adapt by compensatory mutations when the cost of resistance is large, whereas generally beneficial mutations should drive adaptation when the cost of resistance is small. We tested this prediction by determining the genomic mechanisms underpinning adaptation to antibiotic-free conditions in populations of the pathogenic bacterium Pseudomonas aeruginosa that carry costly antibiotic resistance mutations. Whole-genome sequencing revealed that populations founded by high-cost rifampicin-resistant mutants adapted via compensatory mutations in three genes of the RNA polymerase core enzyme, whereas populations founded by low-cost mutants adapted by generally beneficial mutations, predominantly in the quorum-sensing transcriptional regulator gene lasR. Even though the importance of compensatory evolution in maintaining resistance has been widely recognized, our study shows that the roles of general adaptation in maintaining resistance should not be underestimated and highlights the need to understand how selection at other sites in the genome influences the dynamics of resistance alleles in clinical settings.
AU - Qi, Qin
AU - Toll Riera, Macarena
AU - Heilbron, Karl
AU - Preston, Gail
AU - Maclean, R Craig
ID - 1552
IS - 1822
JF - Proceedings of the Royal Society of London Series B Biological Sciences
TI - The genomic basis of adaptation to the fitness cost of rifampicin resistance in Pseudomonas aeruginosa
VL - 283
ER -
TY - JOUR
AB - A modular approach to constructing cryptographic protocols leads to simple designs but often inefficient instantiations. On the other hand, ad hoc constructions may yield efficient protocols at the cost of losing conceptual simplicity. We suggest a new design paradigm, structure-preserving cryptography, that provides a way to construct modular protocols with reasonable efficiency while retaining conceptual simplicity. A cryptographic scheme over a bilinear group is called structure-preserving if its public inputs and outputs consist of elements from the bilinear groups and their consistency can be verified by evaluating pairing-product equations. As structure-preserving schemes smoothly interoperate with each other, they are useful as building blocks in modular design of cryptographic applications. This paper introduces structure-preserving commitment and signature schemes over bilinear groups with several desirable properties. The commitment schemes include homomorphic, trapdoor and length-reducing commitments to group elements, and the structure-preserving signature schemes are the first ones that yield constant-size signatures on multiple group elements. A structure-preserving signature scheme is called automorphic if the public keys lie in the message space, which cannot be achieved by compressing inputs via a cryptographic hash function, as this would destroy the mathematical structure we are trying to preserve. Automorphic signatures can be used for building certification chains underlying privacy-preserving protocols. Among a vast number of applications of structure-preserving protocols, we present an efficient round-optimal blind-signature scheme and a group signature scheme with an efficient and concurrently secure protocol for enrolling new members.
AU - Abe, Masayuki
AU - Fuchsbauer, Georg
AU - Groth, Jens
AU - Haralambiev, Kristiyan
AU - Ohkubo, Miyako
ID - 1592
IS - 2
JF - Journal of Cryptology
TI - Structure preserving signatures and commitments to group elements
VL - 29
ER -
TY - JOUR
AB - Chemokines are the main guidance cues directing leukocyte migration. Opposed to early assumptions, chemokines do not necessarily act as soluble cues but are often immobilized within tissues, e.g., dendritic cell migration toward lymphatic vessels is guided by a haptotactic gradient of the chemokine CCL21. Controlled assay systems to quantitatively study haptotaxis in vitro are still missing. In this chapter, we describe an in vitro haptotaxis assay optimized for the unique properties of dendritic cells. The chemokine CCL21 is immobilized in a bioactive state, using laser-assisted protein adsorption by photobleaching. The cells follow this immobilized CCL21 gradient in a haptotaxis chamber, which provides three dimensionally confined migration conditions.
AU - Schwarz, Jan
AU - Sixt, Michael K
ID - 1597
JF - Methods in Enzymology
TI - Quantitative analysis of dendritic cell haptotaxis
VL - 570
ER -
TY - JOUR
AB - The addition of polysialic acid to N- and/or O-linked glycans, referred to as polysialylation, is a rare posttranslational modification that is mainly known to control the developmental plasticity of the nervous system. Here we show that CCR7, the central chemokine receptor controlling immune cell trafficking to secondary lymphatic organs, carries polysialic acid. This modification is essential for the recognition of the CCR7 ligand CCL21. As a consequence, dendritic cell trafficking is abrogated in polysialyltransferase-deficient mice, manifesting as disturbed lymph node homeostasis and unresponsiveness to inflammatory stimuli. Structure-function analysis of chemokine-receptor interactions reveals that CCL21 adopts an autoinhibited conformation, which is released upon interaction with polysialic acid. Thus, we describe a glycosylation-mediated immune cell trafficking disorder and its mechanistic basis.
AU - Kiermaier, Eva
AU - Moussion, Christine
AU - Veldkamp, Christopher
AU - Gerardy Schahn, Rita
AU - De Vries, Ingrid
AU - Williams, Larry
AU - Chaffee, Gary
AU - Phillips, Andrew
AU - Freiberger, Friedrich
AU - Imre, Richard
AU - Taleski, Deni
AU - Payne, Richard
AU - Braun, Asolina
AU - Förster, Reinhold
AU - Mechtler, Karl
AU - Mühlenhoff, Martina
AU - Volkman, Brian
AU - Sixt, Michael K
ID - 1599
IS - 6269
JF - Science
TI - Polysialylation controls dendritic cell trafficking by regulating chemokine recognition
VL - 351
ER -
TY - JOUR
AB - We show that the Anderson model has a transition from localization to delocalization at exactly 2 dimensional growth rate on antitrees with normalized edge weights which are certain discrete graphs. The kinetic part has a one-dimensional structure allowing a description through transfer matrices which involve some Schur complement. For such operators we introduce the notion of having one propagating channel and extend theorems from the theory of one-dimensional Jacobi operators that relate the behavior of transfer matrices with the spectrum. These theorems are then applied to the considered model. In essence, in a certain energy region the kinetic part averages the random potentials along shells and the transfer matrices behave similar as for a one-dimensional operator with random potential of decaying variance. At d dimensional growth for d>2 this effective decay is strong enough to obtain absolutely continuous spectrum, whereas for some uniform d dimensional growth with d<2 one has pure point spectrum in this energy region. At exactly uniform 2 dimensional growth also some singular continuous spectrum appears, at least at small disorder. As a corollary we also obtain a change from singular spectrum (d≤2) to absolutely continuous spectrum (d≥3) for random operators of the type rΔdr+λ on ℤd, where r is an orthogonal radial projection, Δd the discrete adjacency operator (Laplacian) on ℤd and λ a random potential.
AU - Sadel, Christian
ID - 1608
IS - 7
JF - Annales Henri Poincare
TI - Anderson transition at 2 dimensional growth rate on antitrees and spectral theory for operators with one propagating channel
VL - 17
ER -
TY - JOUR
AB - We prove that whenever A is a 3-conservative relational structure with only binary and unary relations,then the algebra of polymorphisms of A either has no Taylor operation (i.e.,CSP(A)is NP-complete),or it generates an SD(∧) variety (i.e.,CSP(A)has bounded width).
AU - Kazda, Alexandr
ID - 1612
IS - 1
JF - Algebra Universalis
TI - CSP for binary conservative relational structures
VL - 75
ER -
TY - JOUR
AB - In the last decade, induced pluripotent stem (iPS) cells have revolutionized the utility of human in vitro models of neurological disease. The iPS-derived and differentiated cells allow researchers to study the impact of a distinct cell type in health and disease as well as performing therapeutic drug screens on a human genetic background. In particular, clinical trials for Alzheimer's disease (AD) have been often failing. Two of the potential reasons are first, the species gap involved in proceeding from initial discoveries in rodent models to human studies, and second, an unsatisfying patient stratification, meaning subgrouping patients based on the disease severity due to the lack of phenotypic and genetic markers. iPS cells overcome this obstacles and will improve our understanding of disease subtypes in AD. They allow researchers conducting in depth characterization of neural cells from both familial and sporadic AD patients as well as preclinical screens on human cells.
In this review, we briefly outline the status quo of iPS cell research in neurological diseases along with the general advantages and pitfalls of these models. We summarize how genome-editing techniques such as CRISPR/Cas will allow researchers to reduce the problem of genomic variability inherent to human studies, followed by recent iPS cell studies relevant to AD. We then focus on current techniques for the differentiation of iPS cells into neural cell types that are relevant to AD research. Finally, we discuss how the generation of three-dimensional cell culture systems will be important for understanding AD phenotypes in a complex cellular milieu, and how both two- and three-dimensional iPS cell models can provide platforms for drug discovery and translational studies into the treatment of AD.
AU - Mungenast, Alison
AU - Siegert, Sandra
AU - Tsai, Li
ID - 1613
JF - Molecular and Cellular Neuroscience
TI - Modeling Alzheimer's disease with human induced pluripotent stem (iPS) cells
VL - 73
ER -
TY - JOUR
AB - The hippocampus plays a key role in learning and memory. Previous studies suggested that the main types of principal neurons, dentate gyrus granule cells (GCs), CA3 pyramidal neurons, and CA1 pyramidal neurons, differ in their activity pattern, with sparse firing in GCs and more frequent firing in CA3 and CA1 pyramidal neurons. It has been assumed but never shown that such different activity may be caused by differential synaptic excitation. To test this hypothesis, we performed high-resolution whole-cell patch-clamp recordings in anesthetized rats in vivo. In contrast to previous in vitro data, both CA3 and CA1 pyramidal neurons fired action potentials spontaneously, with a frequency of ∼3–6 Hz, whereas GCs were silent. Furthermore, both CA3 and CA1 cells primarily fired in bursts. To determine the underlying mechanisms, we quantitatively assessed the frequency of spontaneous excitatory synaptic input, the passive membrane properties, and the active membrane characteristics. Surprisingly, GCs showed comparable synaptic excitation to CA3 and CA1 cells and the highest ratio of excitation versus hyperpolarizing inhibition. Thus, differential synaptic excitation is not responsible for differences in firing. Moreover, the three types of hippocampal neurons markedly differed in their passive properties. While GCs showed the most negative membrane potential, CA3 pyramidal neurons had the highest input resistance and the slowest membrane time constant. The three types of neurons also differed in the active membrane characteristics. GCs showed the highest action potential threshold, but displayed the largest gain of the input-output curves. In conclusion, our results reveal that differential firing of the three main types of hippocampal principal neurons in vivo is not primarily caused by differences in the characteristics of the synaptic input, but by the distinct properties of synaptic integration and input-output transformation.
AU - Kowalski, Janina
AU - Gan, Jian
AU - Jonas, Peter M
AU - Pernia-Andrade, Alejandro
ID - 1616
IS - 5
JF - Hippocampus
TI - Intrinsic membrane properties determine hippocampal differential firing pattern in vivo in anesthetized rats
VL - 26
ER -
TY - JOUR
AB - We study the discrepancy of jittered sampling sets: such a set P⊂ [0,1]d is generated for fixed m∈ℕ by partitioning [0,1]d into md axis aligned cubes of equal measure and placing a random point inside each of the N=md cubes. We prove that, for N sufficiently large, 1/10 d/N1/2+1/2d ≤EDN∗(P)≤ √d(log N) 1/2/N1/2+1/2d, where the upper bound with an unspecified constant Cd was proven earlier by Beck. Our proof makes crucial use of the sharp Dvoretzky-Kiefer-Wolfowitz inequality and a suitably taylored Bernstein inequality; we have reasons to believe that the upper bound has the sharp scaling in N. Additional heuristics suggest that jittered sampling should be able to improve known bounds on the inverse of the star-discrepancy in the regime N≳dd. We also prove a partition principle showing that every partition of [0,1]d combined with a jittered sampling construction gives rise to a set whose expected squared L2-discrepancy is smaller than that of purely random points.
AU - Pausinger, Florian
AU - Steinerberger, Stefan
ID - 1617
JF - Journal of Complexity
TI - On the discrepancy of jittered sampling
VL - 33
ER -
TY - JOUR
AB - We consider the Bardeen–Cooper–Schrieffer free energy functional for particles interacting via a two-body potential on a microscopic scale and in the presence of weak external fields varying on a macroscopic scale. We study the influence of the external fields on the critical temperature. We show that in the limit where the ratio between the microscopic and macroscopic scale tends to zero, the next to leading order of the critical temperature is determined by the lowest eigenvalue of the linearization of the Ginzburg–Landau equation.
AU - Frank, Rupert
AU - Hainzl, Christian
AU - Seiringer, Robert
AU - Solovej, Jan
ID - 1620
IS - 1
JF - Communications in Mathematical Physics
TI - The external field dependence of the BCS critical temperature
VL - 342
ER -
TY - JOUR
AB - We prove analogues of the Lieb–Thirring and Hardy–Lieb–Thirring inequalities for many-body quantum systems with fractional kinetic operators and homogeneous interaction potentials, where no anti-symmetry on the wave functions is assumed. These many-body inequalities imply interesting one-body interpolation inequalities, and we show that the corresponding one- and many-body inequalities are actually equivalent in certain cases.
AU - Lundholm, Douglas
AU - Nam, Phan
AU - Portmann, Fabian
ID - 1622
IS - 3
JF - Archive for Rational Mechanics and Analysis
TI - Fractional Hardy–Lieb–Thirring and related Inequalities for interacting systems
VL - 219
ER -
TY - JOUR
AB - Ancestral processes are fundamental to modern population genetics and spatial structure has been the subject of intense interest for many years. Despite this interest, almost nothing is known about the distribution of the locations of pedigree or genetic ancestors. Using both spatially continuous and stepping-stone models, we show that the distribution of pedigree ancestors approaches a travelling wave, for which we develop two alternative approximations. The speed and width of the wave are sensitive to the local details of the model. After a short time, genetic ancestors spread far more slowly than pedigree ancestors, ultimately diffusing out with radius ## rather than spreading at constant speed. In contrast to the wave of pedigree ancestors, the spread of genetic ancestry is insensitive to the local details of the models.
AU - Kelleher, Jerome
AU - Etheridge, Alison
AU - Véber, Amandine
AU - Barton, Nicholas H
ID - 1631
JF - Theoretical Population Biology
TI - Spread of pedigree versus genetic ancestry in spatially distributed populations
VL - 108
ER -
TY - JOUR
AB - The plant hormone auxin (indole-3-acetic acid) is a major regulator of plant growth and development including embryo and root patterning, lateral organ formation and growth responses to environmental stimuli. Auxin is directionally transported from cell to cell by the action of specific auxin influx [AUXIN-RESISTANT1 (AUX1)] and efflux [PIN-FORMED (PIN)] transport regulators, whose polar, subcellular localizations are aligned with the direction of the auxin flow. Auxin itself regulates its own transport by modulation of the expression and subcellular localization of the auxin transporters. Increased auxin levels promote the transcription of PIN2 and AUX1 genes as well as stabilize PIN proteins at the plasma membrane, whereas prolonged auxin exposure increases the turnover of PIN proteins and their degradation in the vacuole. In this study, we applied a forward genetic approach, to identify molecular components playing a role in the auxin-mediated degradation. We generated EMS-mutagenized Arabidopsis PIN2::PIN2:GFP, AUX1::AUX1:YFP eir1aux1 populations and designed a screen for mutants with persistently strong fluorescent signals of the tagged PIN2 and AUX1 after prolonged treatment with the synthetic auxin 2,4-dichlorophenoxyacetic acid (2,4-D). This approach yielded novel auxin degradation mutants defective in trafficking and degradation of PIN2 and AUX1 proteins and established a role for auxin-mediated degradation in plant development.
AU - Zemová, Radka
AU - Zwiewka, Marta
AU - Bielach, Agnieszka
AU - Robert, Hélène
AU - Friml, Jirí
ID - 1641
IS - 2
JF - Journal of Plant Growth Regulation
TI - A forward genetic screen for new regulators of auxin mediated degradation of auxin transport proteins in Arabidopsis thaliana
VL - 35
ER -
TY - CONF
AB - A somewhere statistically binding (SSB) hash, introduced by Hubáček and Wichs (ITCS ’15), can be used to hash a long string x to a short digest y = H hk (x) using a public hashing-key hk. Furthermore, there is a way to set up the hash key hk to make it statistically binding on some arbitrary hidden position i, meaning that: (1) the digest y completely determines the i’th bit (or symbol) of x so that all pre-images of y have the same value in the i’th position, (2) it is computationally infeasible to distinguish the position i on which hk is statistically binding from any other position i’. Lastly, the hash should have a local opening property analogous to Merkle-Tree hashing, meaning that given x and y = H hk (x) it should be possible to create a short proof π that certifies the value of the i’th bit (or symbol) of x without having to provide the entire input x. A similar primitive called a positional accumulator, introduced by Koppula, Lewko and Waters (STOC ’15) further supports dynamic updates of the hashed value. These tools, which are interesting in their own right, also serve as one of the main technical components in several recent works building advanced applications from indistinguishability obfuscation (iO).
The prior constructions of SSB hashing and positional accumulators required fully homomorphic encryption (FHE) and iO respectively. In this work, we give new constructions of these tools based on well studied number-theoretic assumptions such as DDH, Phi-Hiding and DCR, as well as a general construction from lossy/injective functions.
AU - Okamoto, Tatsuaki
AU - Pietrzak, Krzysztof Z
AU - Waters, Brent
AU - Wichs, Daniel
ID - 1653
TI - New realizations of somewhere statistically binding hashing and positional accumulators
VL - 9452
ER -
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 -